Title of Invention

A COMPOUND 3'-{N'-[1-3,5-DIMETHYL-PHENYL)-6-TRIFLUOROMETHYL-2-OXO-1,2-DIHYDRO-INDOL-3-YLIDENE]-HYDRAZINO}-2'-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, FOR MODULATING THROMBOPOIETIN ACTIVITY

Abstract Disclosed herein are substituted arylhydrazino compounds, pharmaceutical compositions comprising the same, methods of modulating the activity a thrombopoietin receptor using the same, methods of identifying compounds as thrombopoietin receptor modulators, and methods of treating disease by administering a compound of the invention to a patient in need thereof.
Full Text Field of the Invention
This invention relates to compounds that modulate one or more thrombopoietin activity and/or bind to thrombopoietin receptors; and to methods for making and using such compounds.
Background
Thrombopoietin (TPO), also referred to as c-Mpl ligand, mpl ligand, megapoietin, and megakaryocyte growth and development factor, is a glycoprotein that has been shown to be involved in production of platelets. See e.g., Wendling, F., et. al., Biotherapy 10(4):269-77 (1998); Kuter DJ. et al.. The Oncologist, 1:98-106 (1996); and Metcalf, Nature 369: 519-520 (1994). TPO has been cloned and its amino acid sequence and the cDNA sequence encoding it have been described. See e.g., U.S. 5,766,581; Kuter, D.J. et al., Proc. Natl. Acad. Sci., 91:11104-11108 (1994); de Sauvage F.V., et al., Nature, 369: 533-538 (1994); Lok, S. etal.. Nature 369:565-568 (1994); and Wending, F. et al., Nature, 369: 571-574 (1994).
In certain instances, TPO activity results from binding of TPO to the TPO receptor (also called MPL). The TPO receptor has been cloned and its amino acid sequence has been described. See e.g., Vigon et al., Proc. Natl. Acad. Sci., 89:5640-5644 (1992).
In certain instances, TPO modulators may be useful in treating a variety of hematopoietic conditions, including, but not limited to, thrombocytopenia. See e.g., Baser et al. Blood 89:3118-3128 (1997); Fanucchi et al. New Engl. J. Med. 336:404-409 (1997). For example, patients undergoing certain chemotherapies, including but not limited to chemotherapy and/or radiation therapy for the treatment of cancer, may have reduced platelet levels. In certain instances, treating such patients with a selective TPO modulator increases platelet levels. In certain instances, selective TPO modulators stimulate production of glial cells, which may result in repair of damaged nerve cells.
Certain TPO mimics have been described previously. See e.g., WO

Summary of the Invention
In certain embodiments, the present invention provides a compound of Formula I:
(Figure Removed)
or a pharmaceutically acceptable salt, ester, amid, or prodrug thereof, wherein:
R1 is selected from C02R10, CONR10RU, SO3R10, and a carboxylic acid bioisostere;
R2 and R3 are each independently selected from null, hydrogen, OR12, NR12R13, an optionally substituted C1-C4 aliphatic, an optionally substitutedC1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or R2 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring;
R4 is selected from hydrogen, F, Cl, Br, C1-C4 aliphatic,C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
R5 is selected from hydrogen, OR10, SR10, NHR11, and CO2H;
R6 is selected from hydrogen, OR12, NR12R13, F, Cl, Br, C1-C4 alkyl, C1-C4 haloalkyl,C1-C4 heteroalkyl, and a ring;
R7 is selected from hydrogen, an optionally substituted C1-C8 aliphatic, an optionally substituted C1-C8 haloaliphatic, an optionally substituted C1-C8 heteroaliphatic, an optionally substituted C1-C8 heterohaloaliphatic, an optionally substituted ring, and (CH2)inR14;
R10 is selected from hydrogen, an optionally substituted C1-C4 aliphatic, C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
Rn is selected from hydrogen, SO2R15, C1-C4 aliphatic,C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
R12 and R13 are each independently selected from hydrogen, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4
heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or one of R12 and R13 is an optionally substituted C2-C6 aliphatic or an optionally substituted ring and the other of R12 and Ru is null; or R12 and R13 are linked to form an optionally substituted C3-C8 ring;
R14 is selected from an optionally substituted aryl and an optionally substituted heteroaryl ;
R15 is selected from hydrogen, C1-C3 aliphatic, C1-C3 haloaliphatic, and a ring;
Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted C1-C6 aliphatic, an optionally substituted C1-C6 heteroaliphatic, an optionally substituted phenyl, an optionally substituted heteroaryl, an optionally substituted C3-Cs heterocycle, and an optionally substituted alicyclic,
provided that Y is not-N=CR6- orientated to form a dihydropyrazole;
Z is selected from:
a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl and an
optionally substituted C1-C8 heteroaryl, and
a 1-5 atom spacer of selected from an optionally substituted C1-C6 aliphatic, an
optionally substituted C1-C6 heteroaliphatic, and an optionally substituted C1-C6
haloaliphatic;
m is 0, 1, or 2; and
n isOor 1.
In certain embodiments, the invention provides a compound of Formula I OR a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
R1 is selected from CO2R10, CONR10R11, S03R10, and a carboxylic acid bioisostere selected fromtetrazole, NHSO2R1S, OC(S)NR'°Rn, SC(O)NR10RU, and B
(Figure Removed)
wherein A, B, and C are each independently selected from O, S, and N;
R2 and R3 are each independently selected from hydrogen, OR12, NR12R13, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted ring, and (CH2)mR14; or R2 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring;
R4 is selected from hydrogen, F, Cl, Br, C1-C4 alkyl, C1-C4 haloalkyl,C1-C4 heteroalkyl, and a non-aromatic ring;
R7 is selected from hydrogen, an optionally substituted C1-C8alkyl, an optionally substituted C1-C8haloalkyl, an optionally substituted C1-C8heteroalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted aromatic ring, and (CH2)mR14;

R10 is selected from hydrogen, an optionally substituted C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and a non-aromatic ring;
R11 is selected from hydrogen, S02R15,C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and a non-aromatic ring;
R12 and R13 are each independently selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted non-aromatic ring, and (CH2)mR14; or one of R12 and Ru is an optionally substituted C2-C6 alkyl or an optionally substituted non-aromatic ring, and the other of R12 and R13 is null; or R12 and R13 are linked to form an optionally substituted C3-C8 ring;
R15 is selected from hydrogen, C1-C3 alkyl, C1-C3haloalkyl, and aryl;
Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted C1-C6 alkyl, an optionally substitutedC1-C6heteroalkyl, an optionally substituted C2-C6 alkenyl, an optionally substituted C2-C6 heteroalkenyl, an optionally substituted phenyl, an optionally substituted heteroaryl, an optionally substituted C3-C5 heterocycle, an optionally substituted cycloalkyl, and an optionally substituted cycloalkenyl; and
Z is selected from:
a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl and an
optionally substituted C1-C8 heteroaryl, and
a 1-5 atom spacer of selected from an optionally substituted C1-C6alkyl, an
optionally substituted C1-C6 heteroalkyl, an optionally substituted C1-C6 haloalkyl, an
optionally substituted C2-C6 alkenyl, an optionally substituted C2-C6 heteroalkenyl, an
optionally substituted C2-C6 haloalkenyl, an optionally substituted C2-C6 alkynyl, and an
optionally substituted C2-C6 heteroalkyl.
In certain embodiments, the present invention provides a compound of Formula H:
(Figure Removed)
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
R1 is selected from CO2R10, CONR10RU, SOsR10, and a carboxylic acid bioisostere;
R2 and RJ are each independently selected from null, hydrogen, OR12, NR12R13, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or R2 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring;
R4 is selected from hydrogen, F, Cl, Br, C1-C4 aliphatic, C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
R5 is selected from hydrogen, OR10, SR10, NHR", and C02H;
R6 is selected from hydrogen, OR12, NR12R13, F, Cl, Br, C1-C4 alkyl, C1-C4 haloalkyl,C1-C4 heteroalkyl, and a ring;
R7 is selected from hydrogen, an optionally substituted C1-C8 aliphatic, an optionally substituted C1-C8 haloaliphatic, an optionally substituted C1-C8 heteroaliphatic, an optionally substituted C1-C8 heterohaloaliphatic, an optionally substituted ring, and (CH2),nR14;
R8 and R9 are each independently selected from hydrogen, F, Cl, Br, CO2R10, NO2, CN, SO2R10, (CH2)mR14, C1-C4 aliphatic, C1-C4 haloaliphatic,C1-C4 heteroaliphatic, C1-C4 heterohaloaliphatic, and a ring;
R10 is selected from hydrogen, an optionally substituted C1-C4aliphatic, C1-C4 haloaliphatic,C1-C4 heteroaliphatic, and a ring;
R" is selected from hydrogen, SO2R15, C1-C4 aliphatic, C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
R12 and R13 are each independently selected from hydrogen, an optionally substituted CrC4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or one of R12 and R13 is an optionally substituted C2-C6 aliphatic or an optionally substituted ring and the other of R12 and R13 is null; or R12 and R13 are linked to form an optionally substituted C3-C8ring;
R14 is selected from an optionally substituted aryl and an optionally substituted heteroaoryl;
R15 is selected from hydrogen, C1-C3 aliphatic,C1-C3 haloaliphatic, and a ring;
Q is selected from 0 and S;
X is selected from O, S, NR10, and CRIORn;
Y is selected from:
(Figure Removed)
. ,and
Z is selected from:a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl and an optionally substituted C1-C8 heteroaryl, and
a 1 -5 atom spacer of selected from an optionally substituted C1-C6 aliphatic, an optionally substitutedC1-C6 heteroaliphatic, and an optionally substituted C1-C6 haloaliphatic; misO, 1, or 2; and nis Oor I.
In certain embodiments, the invention provides a compound of Formula n or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
R1 is selected from CO2RJ0. CONR'V, SO3R10, and a carboxylic acid bioisostere selected from tetrazole, NHSOjR'5, OC(S)NR'°R", SC(O)NRIOR", and B "C
(Figure Removed)
wherein A, B, and C are each independently selected from O, S, and N; R2 and R1 are each independentfy selected from hydrogen, OR11, NR12R13, an optionally substituted C1-C4 alkyl, an. optionally substitutedC1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted ring, and (CH2)mR14; or R1 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring; or one of R2 or R3 is null;
R4 is selected from hydrogen, F, a, Br, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl and a non-aromatic ring;
R7 is selected from hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8heteroalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted aromatic ring, and (CH2)0JR1'1;
R8 and R9 are each independently selected from hydrogen, F.-C1, Br, COZ R10, NOZ, CM, SO2 R'°, (CHUJl'4, 0,-C, alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, C1-C4 heterobaloalkyl, and a ring;
R'° is selected from hydrogen, an optionally substituted C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and anon-aromatic ring;
R" is selected from hydrogen, SOZR15, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl; R12 and R13 are each independently selected from hydrogen, an optionally substituted C1-C4 alky!, an optionally substituted CrC4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted non-aromatic ring, and (CH2)nR"; or one of R12 and R13 is an optionally
substituted C2-C6 alkyl or an optionally substituted non-aromatic ring and the other of R12 and R13 is null; or R12 and Ru are linked to form an optionally substituted C3-C8 ring;
R15 is selected from hydrogen, C1-C3 alkyl,C1-C3 haloalkyl, and aryl; and Z is selected from:
a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl and an optionally substituted C1-C8 heteroaryl, and
a 1-5 atom spacer of selected from an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C2-C6 alkenyl, an optionally substituted C2-C6 heteroalkenyl, an optionally substituted C2-C6 haloalkenyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 heteroalkyl.
In certain embodiments, the present invention provides a compound of Formula III:
(Figure Removed)
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
R1 is selected from CO2R10, CONR10Rn, SO3R10, and a carboxylic acid bioisostere;
R2 and R3 are each independently selected from null, hydrogen, OR12, NR12R13, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or R2 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring;
R4 is selected from hydrogen, F, Cl, Br, C1-C4 aliphatic, C1-C4 haloaliphatic, C1-C4 heteroaliphatic, and a ring;
Rs is selected from hydrogen, OR10, SR10, NHR1', and CO2H;
R6 is selected from hydrogen, OR12, NR12R13, F, Cl, Br, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;

R7 is selected from hydrogen, an optionally substituted C1-C8 aliphatic, an optionally substituted C1-C8 haloaliphatic, an optionally substituted C1-C8 heteroaliphatic, an optionally substituted C1-C8 heterohaloaliphatic, an optionally substituted ring, and (CH2)mR14;
R8 and R9 are each independently selected from hydrogen, F, Cl, Br, CO2R10, NO2, CN, SO2R10, (CH2)mR14, C1-C4 aliphatic, C1-C4 haloaliphatic,C1-C4 heteroaliphatic, and C1-C4 heterohaloaliphatic;
R10 is selected from hydrogen, an optionally substituted C1-C4 aliphatic, C1-C4 haloaliphatic, C1-C4heteroaliphatic, and a ring;
R11 is selected from hydrogen, SO2R15, C1-C4 aliphatic, C1-C4haloaliphatic, C1-C4 heteroaliphatic, and a ring;
R12 and R13 are each independently selected from hydrogen, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, an optionally substituted ring, and (CH2)mR14; or one of R12 and R13 is an optionally substituted C2-C6 aliphatic or an optionally substituted ring and the other of R12 and Ru is null; or R12 and R13 are linked to form an optionally substituted C3-C8 ring;
R14 is selected from an optionally substituted aryl and an optionally substituted heteroaryl;
R15 is selected from hydrogen, C1-C3 aliphatic, C1-C3haloaliphatic, and a ring;
misO, 1, or 2; and
nisOor 1.
In certain embodiments, the invention provides a compound of Formula III or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
R1 is selected from C02R10, CONR10R", SO3R10, and a carboxylic acid bioisostere selected from tetrazole, NHSO2R15, OC(S)NR'°Rn, SC(O)NR10RH, and B
(Figure Removed)
wherein A, B, and C are each independently selected from O, S, and N;
R2 and R3 are each independently selected from hydrogen, OR12, NR12R13, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted ring, and (CH2)mRM; or R2 and R3 taken together form an optionally substituted olefin; or R2 and R3 are linked to form an optionally substituted C3-C8 ring;
R4 is selected from hydrogen, F, Cl, Br, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and a non-aromatic ring;
R7 is selected from hydrogen, an optionally substituted C1 -C8 alkyl, an optionally substituted C1 -C8 haloalkyl, an optionally substituted C1 -C8 heteroalkyl, an optionally substituted C1 -C8 heterohaloalkyl, an optionally substituted aromatic ring, and (CH2)niR14;
R8 and R9 are each independently selected from hydrogen, F, Cl, Br, CO2R10, NO2, CN, SO2R10, (CH2)mR14, C1 -C4 alkylC1 -C4 haloalkyl, C1 -C4 heteroalkyl, and C1 -C4 heterohaloalkyl;
R10 is selected from hydrogen, an optionally substituted C1 -C4 alkyl, C1 -C4 haloalkyl, C1 -C4 heteroalkyl and a non-aromatic ring;
R1' is selected from hydrogen, SO2R15, C1 -C4 alkyl, C1 -C4 haloalkyl, and C1 -C4 heteroalkyl, and a non-aromatic ring;
R12 and R13 are each independently selected from hydrogen, an optionally substituted C1 -C4 alkyl, an optionally substituted C1 -C4 haloalkyl, an optionally substituted C1 -C4 heteroalkyl, a non-aromatic ring, and (CH2)mRH; or one of R12 and R1J is an optionally substituted C1-C6 alkyl or a non-aromatic ring, and the other of R12 and R13 is null; or R12 and R13 are linked to form an optionally substituted C1 -C3 ring; and
R15 is selected from hydrogen, C1 -C3 alkyl, C1 -C3 haloalkyl, and aryl.
In certain embodiments, a compound of Formula I, n, or in is a selective TPO modulator. In certain such embodiments, a compound of Formula 1, n, or III is a TPO mimic.
In certain embodiments, the invention provides a selective TPO modulator, fa certain embodiments, the invention provides a selective TPO receptor agonist. In certain embodiments, the invention provides a selective TPO receptor antagonist. In certain embodiments, the invention provides a selective TPO partial agonist. In certain embodiments, the invention provides a selective TPO receptor binding compound. In certain embodiments, the invention provides a TPO mimic. In certain embodiments, the invention provides a tissue-selective selective TPO modulator.
In certain embodiments, the invention provides methods for modulating a TPO activity. Certain such methods comprise contacting a cell with one or more compounds of the present invention. Such methods include, but are not limited to, contacting TPO and/or a TPO receptor with one or more compounds of the present irrvention.
In certain embodiments, the invention provides a method for identifying a compound that is capable of modulating TPO activity comprising contacting a cell capable of a TPO activity with a compound of the present invention and monitoring an effect on the cell. In certain such embodiments, the cell expresses a TPO receptor.
In certain embodiments, the invention provides methods of treating a patient comprising administering to the patient a compound of the present invention. In certain embodiments, such a patient suffers from thrombocytopenia. In certain embodiments, one or more
compounds of the present invention are administered to a patient before, during or after chemotherapy, bone marrow transplantation, and/or radiation therapy. In certain embodiments, one or more compounds of the invention are administered to a patient suffering from aplastic anemia, bone marrow failure, and/or idiopathic thrombocytopenia. In certain embodiments, one or more compounds of the present invention are administered to a patient suffering from a disease of the nervous system. In certain embodiments, one or more compounds of the present invention are administered to patient suffering from amyotrophic lateral sclerosis, multiple sclerosis, or multiple dystrophy. In certain embodiments, one or more compounds of the present invention are administered to a patient with a nerve injury, including, but not limited to, a spinal cord injury.
In certain embodiments, the invention provides pharmaceutical compositions comprising one or more compounds of the present invention and a physiologically acceptable carrier, diluent, or excipient.
Detailed Description of the Preferred Embodiments
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention claimed. Herein, the use of the singular includes the plural unless specifically stated
/
otherwise. Herein, the use of "or" means "and/or" unless stated otherwise. Furthermore, use of the term "including" as well as other forms, such as "includes," and "included," is not limiting.
The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in the application including, but not limited to, patents, patent applications, articles, books, manuals, and treatises are hereby expressly incorporated by reference in their entirety for any purpose. Definitions
Unless specific definitions are provided, the nomenclatures utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those known in the art. Standard chemical symbols are used interchangeably with the full names represented by such symbols. Thus, for example, the terms "hydrogen" and "H" are understood to have identical meaning. Standard techniques may be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients. Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Reactions and purification techniques may be performed e.g., using kits according to manufacturer's specifications or as commonly accomplished in the art or as described herein. The foregoing techniques and procedures may be generally
performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. See e.g., Sambrook et al. Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)), which is incorporated herein for any purpose.
As used herein, the following terms are defined with the following meanings, unless expressly stated otherwise.
The term "selective binding compound" refers to a compound that selectively binds to any portion of one or more target.
The term "selective TPO receptor binding compound" refers to a compound that selectively binds to any portion of a TPO receptor.
The term "selectively binds" refers to the ability of a selective binding compound to bind to a target receptor with greater affinity than it binds to a non-target receptor. In certain embodiments, specific binding refers to binding to a target with an affinity that is at least 10, 50,100, 250, 500, or 1000 times greater than the affinity for a non-target.
The term "target receptor" refers to a receptor or a portion of a receptor capable of being bound by a selective binding compound. In certain embodiments, a target receptor is a TPO receptor.
The term "modulator" refers to a compound that alters or elicits an activity. For example, the presence of a modulator may result in an increase or decrease in the magnitude of a certain activity compared to the magnitude of the activity in the absence of the modulator. In certain embodiments, a modulator is an inhibitor, which decreases the magnitude of one or more activities. In certain embodiments, an inhibitor completely prevents one or more biological activities. In certain embodiments, a modulator is an activator, which increases the magnitude of at least one activity. In certain embodiments the presence of a modulator results in a activity that does not occur in the absence of the modulator.
The term "selective modulator" refers to a compound that selectively modulates a target activity.
The term "selective TPO modulator" refers to a comppund that selectively modulates at least one TPO activity. The term selective TPO modulator includes, but is not limited to 'TPO mimic" which refers to a compound, the presence of which results in at least one TPO activity.
The term "selectively modulates" refers to the ability of a selective modulator to modulate a target activity to a greater extent than it modulates a non-target activity.

The term "target activity" refers to a biological activity capable of being modulated by a selective modulator. Certain exemplary target activities include, but are not I imited to, binding affinity; signal transduction; enzymatic activity; transcription of one or more geaes; the proliferation and/or differentiation of cells, including, but not limited to progenitor cells; generation of platelets; and alleviation of symptoms of a disease or condition.
The term "TPO activity" refers to a biological activity that results, either directly or indirectly from the presence of TPO. Exemplary TPO activities include, but are not limited to, proliferation and or differentiation of progenitor cells to produce platelets; hematopoiesis; growth and/or development of glial cells; repair of nerve cells; and alleviation of« thrombocytopenia.
The term "thrombocytopenia" refers to a condition wherein the concentration of platelets in the blood of a patient is below what is considered normal for a healthy patient. In certain embodiments, thrombocytopenia is a platelet count less than 450,000, 400,000, 350,000, 300,000, 250,000, 200,000, 150,000, 140,000, 130,000, 120,000, 110,000, 100,000, 75,OOO, or 50,000 platelets per microliter of blood.
The term "receptor mediated activity" refers any biological activity that results, either directly or indirectly, from binding of a ligand to a receptor.
The term "agonist" refers to a compound, the presence of which results in a biological activity of a receptor that is the same as the biological activity resulting from the presence of a naturally occurring ligand for the receptor.
The term "partial agonist" refers to a compound, the presence of which results in a biological activity of a receptor that is of the same type as that resulting from the presence of a naturally occurring ligand for the receptor, but of a lower magnitude.
The term "antagonist" refers to a compound, the presence of which results in a decrease in the magnitude of a biological activity of a receptor. In certain embodiments, the presence of an antagonist results in complete inhibition of a biological activity of a receptor.
The term "aliphatic," alone or in combination, refers to a straight or branched chain comprising at least one carbon atom. Aliphatics include alkyls, alkenyls, and alkjoryls. In certain embodiments, aliphatics are optionally substituted. Aliphatics include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, ethynyl, butynyl, propynyl, and the like, each of which may be optionally substituted. As used herein, aliphatic is not intended to include cyclic groups.
The term "alkyl," alone or in combination, refers to a fully saturated aliphatic. In certain embodiments, alkyls are optionally substituted. In certain embodiments, an alkyl comprises 1 to 20 carbon atoms (whenever it appears herein, a numerical range, such as "1 to 20" or
"C1-C20", refers to each integer in the given range; e.g., "C1-C20 alkyl" means that an alkyl group comprising only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms). Examples of alkyls include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, tert-amyl, pentyl, hexyl, heptyl, octyl and the like.
The term "alkenyl," alone or in combination, refers to an aliphatic having one or more carbon-carbon double-bonds. In certain embodiments, alkenyls are optionally substituted. Examples of alkenyls include, but are not limited to, ethenyl, propenyl, 1,4-butadienyl, and the like.
The term "alkynyl," alone or in combination, refers to an aliphatic having one or more carbon-carbon triple-bonds. In certain embodiments, alkynyls are optionally substituted. Examples of alkynyls include, but are not limited to, ethynyl, propynyl, butynyl, and the like.
The term "haloaliphatic," alone or in combination, refers to an aliphatic in which at least one hydrogen atom is replaced with a halogen atom. In certain embodiments in which two or more hydrogen atom are replaced with halogen atoms, the halogen atoms are all the same as one another. In certain such embodiments, the halogen atoms are not all the same as one another. Haloaliphatics include haloalkyls, haloalkenyls, and haloalkynyls. In certain embodiments, haloaliphatics are optionally substituted, in addition to the hydrogen/halogen substitution. The term "haloaliphatic" also includes perhaloaliphatic, in which all of the hydrogen atoms of the aliphatic are replaced by halogen atoms. Examples of perhaloaliphatic include trichloromethyl, pentacholorethyl, etc.
The term "heteroaliphatic," alone or in combination, refers to a group comprising an aliphatic and one or more heteroatoms. Certain heteroaliphatics are acylaliphatics, in which the one or more heteroatoms is not within an aliphatic chain. Heteroaliphatics include heteroalkyls, including, but not limited to acylalkys; heteroalkenyls, including, but not limited to, acylalkenyls; and heteroalkynyls, including, but not limited acylalkynyls. Examples of heteraliphatics include, but are not limited to, CH3C(=O)CH2-, CH3C(==O)CH2CH2-, CH3CH2C(=O)CH2CH2-, CH3C(=O)CH2CH2CH2-, CH3OCH2CH2-5 CH3NHCHr, and the like. In certain embodiments, heteroaliphatics are optionally substituted.
The term "heterohaloaliphatic" refers to a heteroaliphatic in which at least one hydrogen atom is replaced with a halogen atom. Heterohaloaliphatics include heterohaloalkyls, heterohaloalkenyls, and heterohaloalkynyls. In certain embodiments, heterohaloaliphatics are optionally substituted.
The term "olefin" refers to a C=C bond. The term "together form an olefin" refers to instances where two groups are bound to the same carbon atom and one of those two groups is =C and the other of those two groups is null. For example, if R' and R" in the structure

below together form an olefin:
(Figure Removed)
the resulting structure is:
(Figure Removed)
wherein R'" and R"" represent hydrogen. Olefms may be optional substituted, in which case R'" and R"" above are independently selected from hydrogen and an optional substituent.
The term "carbocycle" refers to a group comprising a covalently closed ring, wherein each of the atoms forming the ring is a carbon atom. Carbocylic rings may be formed by three, four, five, six, seven, eight, nine, or more than nine carbon atoms. Carbocycles may be optionally substituted.
The term "heterocycle" refers to a group comprising a covalently closed ring wherein at least one atom forming the ring is a carbon atom and at least one atom forming the ring is a heteroatom. Heterocyclic rings may be formed by three, four, five, six, seven, eight, nine, or more than nine atoms. Any number of those atoms may be heteroatorns (i,e., a heterocyclic ring may comprise one, two, three, four, five, six, seven, eight, nine, or more than nine heteroatorns). Herein, whenever the number of carbon atoms in a heterocycle is indicated (e.g., C1-C6 heterocycle), at least one other atom (the heteroatom) must be present in the ring. Designations such as "C1-C6 heterocycle" refer only to the number of carbon atoms in the ring and do not refer to the total number of atoms in the ring. It is understood that the heterocylic ring will have additional heteroatorns in the ring. In heterocycles comprising two or more heteroatorns, those two or more heteroatorns may be the same or different from one another. Heterocycles may be optionally substituted. Binding to a heterocycle can be at a heteroatom or via a carbon atom. Examples of heterocycles include, but are not limited to the following:

(Figure Removed)
wherein D, E, F, and G independently represent a heteroatom. Each of D, E, F, and G may be the same or different from one another.
The term "heteroatom" refers to an atom other than carbon or hydrogen. Heteroatoms are typically independently selected from oxygen, sulfur, nitrogen, and phosphorus, but are not limited to those atoms. In embodiments in which two or more heteroatoms are present, the two or more heteroatoms may all be the same as one another, or some or all of the two or more heteroatoms may each be different from the others.
The term "aromatic" refers to a group comprising a covalently closed planar ring having a delocalized π-electron system comprising 4n+2π electrons, where n is an integer. Aromatic rings may be formed by five, six, seven, eight, nine, or more than nine atoms. Aromatics may be optionally substituted. Examples of aromatic groups include, but are not limited to phenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl, indenyl, and indanyl. The term, aromatic includes, for example, benzenoid groups, connected via one of the ring-forming carbon, atoms, and optionally carrying one or more substituents selected from an aryl, a heteroaryl, a. cycloalkyl, a non-aromatic heterocycle, a halo, a hydroxy, an amino, a cyano, a nitro, an. alkylamido, an acyl, a C1-6alkoxy, a C1-6 alkyl, a C1-6 hydroxyalkyl, a C1-6 aminoalkyl, a C1-6 alkylamino, an alkylsulfenyl, an allcylsulfmyl, an alkylsulfonyl, an sulfamoyl, or a trifluoromethyl. In certain embodiments, an aromatic group is substituted at one or more of the para, meta, and/or ortho positions. Examples of aromatic groups comprising substitutions include, but are not limited. to, phenyl, 3-halophenyl, 4-halophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-aminophenyl, 4-aminophenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-
trifluoromethoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, dimethylphenyl, naphthyl, hydroxynaphthyl, hydroxymethylphenyl, (trifluoromethyl)phenyl, alkoxyphenyl, 4-morpholin-4-ylphenyl, 4-pyrrolidin-l-ylphenyl, 4-pyrazolylphenyl, 4-triazolylph.enyl, and 4-(2-oxopyrrolidin-l-yl)phenyl.
The term "aryl" refers to an aromatic ring wherein each of the atoms forming the ring is a carbon atom. Aryl rings may be formed by five, six, seven, eight, nine, or more than nine carbon atoms. Aryl groups may be optionally substituted.
The term "heteroaryl" refers to an aromatic heterocycle. Heteroaryl rings may be formed by three, four, five, six, seven, eight, nine, or more than nine atoms. Heteroaryls may be optionally substituted. Examples of heteroaryl groups include, but are not limited to, aromatic C3.8 heterocyclic groups comprising one oxygen or sulfur atom or up to four nitrogen atoms, or a combination of one oxygen or sulfur atom and up to two nitrogen, atoms, and their substituted as well as benzo- and pyrido-fused derivatives, for example, connected via one of the ring-forming carbon atoms. In certain embodiments, heteroaryl groups are optionally substituted with one or more substituents, independently selected from halo, hydroxy, arnino, cyano, nitro, alkylamido, acyl, C1-6-alkoxy, C1-6-alkyl, C1-6-hydroxyalkyl, C1-6-aminoalkyl, C1-6-alkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or trifluoromethyl. Examples of heteroaryl groups include, but are not limited to, unsubstituted and mono- or di-substituted derivatives of furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole, isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazole, quinoline, isoquinoline, pyridazine, pyrimidine, purine and pyrazine, furazan, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, triazole, benzotriazole, pteridine, phenoxazole, oxadiazole, benzopyrazole, quinolizine, cinnoline, phthalazine, quinazoline, and quinoxaline. In some embodiments, the substituents are halo, hydroxy, cyano, O-C1-6-alkyl, C1-6-alkyl, hydroxy-C1-6-alkyl, and amino-C1-6-alkyl.
The term "non-aromatic ring" refers to a group comprising a covalentiy closed ring that is not aromatic.
The term "alicyclic" refers to a group comprising a non-aromatic ring wherein each of the atoms forming the ring is a carbon atom. Alicyclic rings may be formed by three, four, five, six, seven, eight, nine, or more than nine carbon atoms. In certain embodiments, alicyclics are optionally substituted. In certain embodiments, an alicyclic comprises one or more unsaturated bonds. Alicyclics include cycloalkyls, cycloalkenyls, and cycloalkynyls. Examples of alicyclics include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclopentadiene, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, cycloheptane, and cycloheptene. In certain embodiments, alicylcic rings are optionally substituted.

The term "non-aromatic heterocycle" refers to a group comprising a non-aromatic ring wherein one or more atoms forming the ring is a heteroatom. Non-aromatic heterocyclic rings may be formed by three, four, five, six, seven, eight, nine, or more than nine atoms. Non-aromatic heterocycles may be optionally substituted. In certain embodiments, non-aromatic heterocycles comprise one or more carbonyl or thiocarbonyl groups such as, for example, oxo- and thio-containing groups. Examples of non-aromatic heterocycles include, but are not limited to, lactams, lactones, cyclic imides, cyclic thioimides, cyclic carbamates, tetrahydrothiopyran, 4H-pyran, tetrahydropyran, piperidine, 1,3-dioxin, 1,3-dioxane, 1,4-dioxin, 1,4-dioxane, piperazine, 1,3-oxathiane, 1,4-oxathiin, 1,4-oxathiane, tetrahydro-l,4-thiazine, 2H-l,2-oxazine , maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, morpholine, trioxane, hexahydro-l,3,5-triazine, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, pyrrolidone, pyrrolidione, pyrazoline, pyrazolidine, imidazoline, imidazolidine, 1,3-dioxole, 1,3-dioxolane, 1,3-dithiole, 1,3-dithiolane, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, and 1,3-oxathiolane.
The term "arylalkyl" refers to a group comprising an aryl group bound to an alkyl group.
The term "ring" refers to any covalently closed structure. Rings include, for example, carbocycles (e.g., aryls and alicyclics), heterocycles (e.g., heteroaryls and non-aromatic heterocycles), aromatics (e.g., aryls and heteroaryls), and non-aromatics (e.g., alicyclics and non-aromatic heterocycles). Rings may be optionally substituted. Rings may form part of a ring system.
The term "ring system" refers to two or more rings, wherein two or more of the rings are fused. The term "fused" refers to structures in which two or more rings share one or more bonds.
The term "null" refers to a group being absent from a structure. For example,
in the structure
(Figure Removed)
where in certain instances X is N, if X is N, one of R' or R" is null, meaning that only three groups are bound to the N.
The term "carboxylic acid bioisostere" refers to a group that is biologically equivalent to a carboxylic acid. For example, carboxylic acid bioisosteres include, but are not limited to, tetrazole, NHSO2R15, OC(S)NR10Rn, SC(0)NR10Rn, thiazolidinedione, oxazolidinedione, and l-oxa-2,4-diazolidine-3,5-dione. In certain embodiments, a carboxylic acid

bioisoster comprises the following structure:
(Figure Removed)
wherein A, B, and C are each independently selected from O, S, and N.
The term "spacer" refers to an atom or group of atoms that separate two or more groups from one another by a desired number of atoms. For example, in certain embodiments, it may be desirable to separate two or more groups by one, two, three, four, five, six, or more than six atoms. In such embodiments, any atom or group of atoms may be used to separate those groups by the desired number of atoms. In certain embodiments, spacers are optionally substituted. In certain embodiments, a spacer comprises an aliphatic. In certain embodiments, a spacer comprises atoms that are part of a ring.
Solely for the purposes of illustration, and without limiting the above definition, some examples of spacers are provided. Examples of 1-atom spacers include, but are not
limited to, the following:

(Figure Removed)
where A and B represent groups which are separated by the desired number of atoms. Examples of 2-atom spacers include, but are not limited to, the following:
(Figure Removed)
where A and B represent groups which are separated by the desired number of atoms. Examples of 3-atom spacers include, but are not limited to, the following:




where A and B represent groups that are separated by the desired number of atoms.In certain embodiments, a spacer separates atoms in a ring. For example, in the
(Figure Removed)
structure:

B , where Q is a 1-atom spacer, the resulting ring is a three-membered ring comprising A, B, and Q, where Q may be optionally substituted. An example of such a structure includes, but is not limited to:
(Figure Removed)
If Q is a 2-atom spacer, then a four-membered ring results; if Q is a three atom spacer, then a five-membered ring results; if Q is a four atom spacer, then a six-membered ring results; if Q is a five atom spacer, then a seven-membered ring results; if Q is a six atom spacer, then an eight-membered ring results; and so on. In certain embodiments, a spacer in a ring comprises a ring, such that the ring formed by the spacer and the ring comprised by the spacer are fused. For example, referring to the structure above where Q is a 3-atom spacer comprising a fused ring includes, but is not limited to, structures such as:

(Figure Removed)
where the fused ring can be fused at any bond of the spacer. Such a fused ring may be optionally substituted and may be heterocyclic or carbocyclic.
As is evident from the above examples, the atoms of a spacer that create the desired separation may themselves be part of a group. That group may be, for example, an aliphatic, heteroaliphatic, haloaliphatic, heterohaloaliphatic, alicyclic, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, or substituted alkyl all of which are optionally substituted. Thus, the term "1-5 atom spacer" refers to a spacer that separates two groups by 1, 2, 3, 4, or 5 atoms and does not indicate the total size of the group that constitutes the spacer.
the resulting ring includes A, B, the carbon atom to which both A and B are bound, and a linking group. Unless otherwise indicated, that linking group may be of any length and may be optionally
The term "linked to form a ring" refers to the circumstance where two atoms that are bound either to a single atom or to atoms that are themselves ultimately bound, are each bound to a linking group, such that the resulting structure forms a ring. That resulting ring comprises the two atoms, the atom (or atoms) that previously linked those atoms, and the linker. For example, if A and B below are "linked to form a ring"
(Figure Removed)

substituted. Referring to the above example, resulting structures include, but are not limited to:

(Figure Removed)
, and the like.
In certain embodiments, the two atoms that are linked to form a ring are not bound to the same atom. For example, if A and B, below, are linked to form a ring:

•, the resulting ring comprises A, B, the 3 carbon atoms that already link A and B, and a linking group. Examples of resulting structures include, but are not limited to:
(Figure Removed)
•, and the like.
The substituent "R" appearing by itself and without a number designation refers to a substituent selected from alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and non-aromatic heterocycle (bonded through a ring carbon).
The term "0-carboxy" refers to a group of formula RC(=O)O-.
The term "C-carboxy" refers to a group of formula -C(=O)OR.
The term "acetyl" refers to a group of formula -C(=O)CH3.
The term "trihalomethanesulfonyl" refers to a group of formula X3CS(=O)2-where X is a halogen.
The term "cyano" refers to a group of formula -CN.
The term "isocyanato" refers to a group of formula -NCO.
The term "thiocyanato" refers to a group of formula -CNS.
The term "isothiocyanato" refers to a group of formula -NCS.
The term "sulfonyl" refers to a group of formula -S(=O)-R.
The term "S-sulfonamido" refers to a group of formula -S(=0)2NR.
The term "N-sulfonamido" refers to a group of formula RS(=0)2NH-.
The term "trihalomethanesulfonamido" refers to a group of formula X3CS(=O)2NR-.
The term "0-carbamyl" refers to a group of formula -OC(=0)-NR.
The term "N-carbamyl" refers to a group of formula ROC(=0)NH-.
The term "0-thiocarbamyl" refers to a group of formula -OC(=S)-NR.

The term "N-thiocarbamyl" refers to a group of formula ROC(=S)NH-.
The term "C-amido" refers to a group of formula -C(=O)-NR2.
The term "N-amido" refers to a group of formula RC(=O)NH-.
The term "ester" refers to a chemical moiety with formula -(R)n-COOR', where R and R' are independently selected from alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and non-aromatic heterocycle (bonded through a ring carbon), where n is 0 or 1.
The term "amide" refers to a chemical moiety with formula -(R)n-C(O)NHR' or -(R)n-NHC(O)R', where R and R' are independently selected from alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon), where n is 0 or 1. In certain embodiments, an amide may be an arnino acid or a peptide.
The terms "amine," "hydroxy," and "carboxyl" include such groups that have been esterified or amidified. Procedures and specific groups used to achieve esterification and amidification are known to those of skill in the art and can readily be found in reference sources such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, which is incorporated herein in its entirety.
Unless otherwise indicated, the term "optionally substituted," refers to a group in which none, one, or more than one of the hydrogen atoms has been replaced with one or more group(s) are independently selected from: alkyl, heteroalkyl, haloalkyl, heteroholoalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, and amino, including mono- and di-substituted amino groups, and the protected derivatives of amino groups. Such protective derivatives (and protecting groups that may form such, protective derivatives) are known to those of skill in the art and may be found in references such as Greene and Wuts, above. In embodiments in which two or more hydrogen atoms have been substituted, the substituent groups may be linked to form a ring.
The term "carrier" refers to a compound that facilitates the incorporation of another compound into cells or tissues. For example, dimethyl sulfoxide (DMSO) is a commonly used carrier for improving incorporation of certain organic compounds into cells or tissues.
The term "pharmaceutical agent" refers to a chemical compound or composition capable of inducing' a desired therapeutic effect in a patient. In certain embodiments, a pharmaceutical agent comprises an active agent, which is the agent that induces the desired therapeutic effect. In certain embodiments, a pharmaceutical agent comprises a prodrug. In certain

embodiments, a pharmaceutical agent comprises inactive ingredients such as carriers, excipients, and the like.
The term "pharmaceutical composition" refers to a pharmaceutical agent together with one or more inactive ingredient for pharmaceutical administration, such as a carrier, excipient, or the like.
The term "therapeutically effective amount" refers to an amount of a pharmaceutical agent or composition sufficient to achieve a desired therapeutic effect.
The term "prodrug" refers to an pharmaceutical agent that is converted from a less active form into a corresponding more active form in vivo.
The term "pharmaceutically acceptable" refers to a formulation of a compound that does not significantly abrogate the biological activity, a pharmacological activity and/or other properties of the compound when the formulated compound is administered to a patient. In certain embodiments, a pharmaceutically acceptable formulation does not cause significant irritation to a patient.
The term "co-administer" refers to administering more than one pharmaceutical agent to a patient. In certain embodiments, co-administered pharmaceutical agents are administered together in a single dosage unit. In certain embodiments, co-administered pharmaceutical agents are administered separately. In certain embodiments, co-administered pharmaceutical agents are administered at the same time. In certain embodiments, co-administered pharmaceutical agents are administered at different times.
The term "patient" includes human and animal subjects.
The term "substantially pure" means an object species (e.g., compound) is the predominant species present (i.e., on a molar basis it is more abundant than any other individual species in the composition). In certain embodiments, a substantially purified fraction is a composition wherein the object species comprises at least about 50 percent (on a molar basis) of all species present. In certain embodiments, a substantially pure composition will comprise more than about 80%, 85%, 90%, 95%, or 99% of all species present in the composition. In certain embodiments, the object species is purified to essential homogeneity (contaminant species cannot be detected in the composition by conventional detection methods) wherein the composition consists essentially of a single species.
The term "tissue-selective" refers to the ability of a compound to modulate a biological activity in one tissue to a greater or lesser degree than it modulates a biological activity in another tissue. The biological activities in the different tissues may be the same or they may be different. The biological activities in the different tissues may be mediated by the same type of target receptor. For example, in certain embodiments, a tissue-selective compound may modulate

receptor mediated biological activity in one tissue and fail to modulate, or modulate to a lesser degree, receptor mediated biological activity in another tissue type.
The term "monitoring" refers to observing an effect or absence of any effect. In certain embodiments, one monitors cells after contacting those cells with a compound of the present invention. Examples of effects that may be monitored include, but are not limited to, changes in cell phenotype, cell proliferation, receptor activity, or the interaction between a receptor and a compound known to bind to the receptor.
The term "cell phenotype" refers to physical or biological characteristics of a cell. Examples of characteristics that constitute phenotype included, but are not limited to, cell size, cell proliferation, cell differentiation, cell survival, apoptosis (cell death), or the utilization of a metabolic nutrient (e.g., glucose uptake). Certain changes or the absence of changes in cell phenotype are readily monitored using techniques known in the art.
The term "cell proliferation" refers to the rate at which cells divide. In certain embodiments, cells are in situ in an organism. In certain, embodiments, cell are grown in vitro in a vessel. The number of cells growing in a vessel can be quantified by a person skilled in the art (e.g., by counting cells in a defined area using a microscope or by using laboratory apparatus that measure the density of cells in an appropriate medium). One skilled in that art can calculate cell proliferation by determining the number of cells at two or more times.
The term "contacting" refers to bringing two or more materials into close enough proximity that they may interact. In certain embodiments, contacting can be accomplished in a vessel such as a test tube, a petri dish, or the like. In certain embodiments, contacting may be performed in the presence of additional materials. In certain embodiments, contacting may be performed in the presence of cells. In certain of such embodiments, one or more of the materials that are being contacted may be inside a cell. Cells may be alive or may dead. Cells may or may not be intact.
Certain compounds
Certain compounds that modulate one or more TPO activity and/or bind to TPO receptors play a role in health. In certain embodiments, compounds of the present invention are useful for treating any of a variety of diseases or conditions.
In certain embodiments, the present invention provides selective TPO modulators. In certain embodiments, the invention provides selective TPO receptor binding agents. In certain embodiments, the invention provides methods of making and methods of using selective TPO modulators and/or selective TPO receptor binding agents. In certain embodiments, selective TPO modulators are agonists, partial agonists, and/or antagonists for the TPO receptor.

In certain embodiments, the present invention relates to compounds of Formula
I, II, or III:

(Figure Removed)
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
In certain embodiments, R1 is selected from hydrogen, CO2R10, CONR10RU, SO3R10, and a carboxylic acid bioisostere. In certain embodiments in which R1 is a carboxylic acid bioisostere, R1 is selected from tetrazole, NHSO2R15, OC(S)NR10RU, SC(O)NR10RU, thiazolidinedione, oxazolidinedione, and l-oxa-2,4-diazolidine-3,5-dione.
Li certain embodiments, R2 and R3 are each independently selected from hydrogen, OR12, MR12R13, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, (CH2)mR14, an optionally substituted ring, and null. In certain such embodiments, R2 and R3 are each independently selected from an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl. In certain embodiments, R2 and R3 taken together form an optionally substituted olefin. In certain embodiments, R2 and R3 are linked to form an optionally substituted C3-C8 ring. In certain such embodiments, R2 and R3 are linked to form an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic, OT an optionally substituted non-aromatic ring. In certain such embodiments, R2 and R3 are linked to
form an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, or an optionally substituted non-aromatic heterocyclic. In certain embodiments, R2 and R3 are linked to form an optionally substituted aryl or an optionally substituted heteroaryl. In certain embodiments, R2 and R3 are linked to form an optionally substituted aryl. In certain embodiments, R2 and R3 are linked to form an aryl.
In certain embodiments, R4 is selected from hydrogen, F, Cl, Br, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4 heteroaliphatic, and an optionally substituted ring. In certain such embodiments, R4 is selected from optionally substituted C1-C4 alkyl, optionally substituted C1-C4 haloalkyl, and optionally substituted C1-C4 heteroalkyl.
In certain embodiments, R5 is selected from hydrogen, OR10, SR10, NHR11, and CO,H.
fa certain embodiments, R6 is selected from hydrogen, OR12, NR12R13, F, Cl, Br, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4heteroaliphatic, and an optionally substituted ring. In certain such embodiments, R6 is selected from optionally substituted C1-C4alkyl, optionally substituted C1-C4 haloalkyl, and optionally substituted C1-C4 heteroalkyl. In certain embodiments, R6 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R6 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. ' In certain embodiments, R6 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. In certain embodiments, R6 is selected from an optionally substituted aryl. La certain embodiments, R6 is an aryl.
In certain embodiments, R7 is selected from hydrogen, an optionally substituted C1-C8 aliphatic, an optionally substituted C1-C8 haloaliphatic, an optionally substituted C1-C8 heteroaliphatic, an optionally substituted C1-C8 heterohaloaliphatic, an optionally substituted ring, and (CH2)mR14. In certain such embodiments, R7 is selected from an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heteroalkyl, and an optionally substituted C1-C8 heterohaloalkyl. In certain embodiments, R7 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R7 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-arornatic heterocyclic. In certain embodiments, R7 is selected from an optionally substituted aryl and an optionally substituted
heteroaryl. In certain embodiments, R7 is selected from an optionally substituted aryl. In certain such embodiments, R7 is selected from an aryl ring optionally fused to one or more additional rings. In certain embodiments, R7 is an aryl. In certain embodiments, R7 is an optionally substituted phenyl ring.
In certain embodiments, R8 and R9 are each independently selected from hydrogen, F, Cl, Br, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4 heteroaliphatic, optionally substituted C1-C4 heterohaloaliphatic, and an optionally substituted ring. In certain such embodiments, R8 and/or R9 is independently selected from optionally substituted C1-C4 alkyl, optionally substituted C1-C4 haloalkyl, optionally substituted C1-C4 heteroalkyl, and optionally substituted C1-C4 heterohaloalkyl. In certain embodiments, R8 and/or R9 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring, In certain such embodiments, R8 and/or R9 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. In certain embodiments, R8 and/or R9 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. fa certain embodiments, R8 and/or R9 is selected from an optionally substituted aryl. fa certain embodiments, R8 and/or R9 is an aryl.
fa certain embodiments, R'° is selected from hydrogen, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4 heteroaliphatic, optionally substituted C1-C4 heterohaloaliphatic, an optionally substituted ring, fa certain such embodiments, R10 is selected from optionally substituted C1-C4 alkyl, optionally substituted C1-C4 haloalkyl, optionally substituted C1-C4 heteroalkyl, and optionally substituted C1-C4 heterohaloalkyl. fa certain embodiments, R10 is selected from an optionally substituted ring, fa certain such embodiments, R10 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring, fa certain such embodiments, R10 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. fa certain embodiments, R10 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. fa certain embodiments, R10 is selected from an optionally substituted aryl. fa certain embodiments, R10 is an aryl.
fa certain embodiments, R" is selected from hydrogen, SO2R15, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4 heteroaliphatic, optionally substituted C1-C4 heterohaloaliphatic, and an optionally substituted ring. In certain such embodiments, R11 is selected from optionally substituted C1-C4 alkyl, optionally
substituted C1-C4 haloalkyl, optionally substituted C1-C4 heteroalkyl, and optionally substituted C1-C4 heterohaloalkyl. In certain embodiments, R" is selected from an. optionally substituted ring. In certain such embodiments, R" is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R11 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. In certain embodiments, R11 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. In certain embodiments, R11 is selected from an optionally substituted aryl. In certain embodiments, Rn is an aryl.
In some embodiments, R12 and R13 are each independently selected from hydrogen, optionally substituted C1-C4 aliphatic, optionally substituted C1-C4 haloaliphatic, optionally substituted C1-C4 heteroaliphatic, optionally substituted. C1-C4 heterohaloaliphatic, an optionally substituted ring, and (CH2)mR14. In certain such embodiments, R12 and/or R13 is independently selected from optionally substituted C1-C4 alkyl, optionally substituted C1-C4 haloalkyl, optionally substituted C1-C4 heteroalkyl, and optionally substituted C1-C4 heterohaloalkyl. In certain embodiments, R12 and/or R13 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R12 and/or R13 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. In certain embodiments, R12 and/or R13 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. In certain embodiments, R12 and/or R13 is selected from an optionally substituted aryl. In certain embodiments, R12 and/or R13 is an aryl. In certain embodiments, one of R12 or R13 is a ring and the other of R12 and R13 is hydrogen.
In certain embodiments, R12 and R13 are linked to form an optionally substituted C2-C8 heterocycle. In certain embodiments, R12 and R13 are linked to form an optionally substituted C2-C8 heteroaryl. In certain embodiments, R12 and R13 are linked to form an optionally substituted C2-C8non-aromatic heterocycle.
In certain embodiments, R14 is selected from an optionally substituted ring. In certain such embodiments, R14 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R14 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. In certain embodiments, R14 is selected from an optionally substituted
aryl and an optionally substituted heteroaryl. In certain embodiments, R14 is selected from an optionally substituted aryl. In certain embodiments, R14 is an aryl.
In certain embodiments, R15 is selected from hydrogen, optionally substituted C1-C3 aliphatic, optionally substituted C1-C3 haloaliphatic, and optionally substituted ring. In certain such embodiments, R15 is selected from optionally substituted C1-C3 alkyl, and optionally substituted C1-C3 haloalkyl. In certain embodiments, R15 is an optionally substituted aryl. La certain embodiments, R15 is selected from an alkyl, a haloalkyl, an alicyclic, and an aryl. In certain embodiments, R15 is selected from an optionally substituted ring. In certain such embodiments, R15 is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, and optionally substituted aromatic, and an optionally substituted non-aromatic ring. In certain such embodiments, R15 is selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted alicyclic, and an optionally substituted non-aromatic heterocyclic. In certain embodiments, R15 is selected from an optionally substituted aryl and an optionally substituted heteroaryl. In certain embodiments, R15 is selected from an optionally substituted aryl. In certain embodiments, R15 is an aryl.
In certain embodiments, Y is a 1, 2, 3, 4, 5, 7, or 8 atom spacer. In certain embodiments, Y is a 1-4 atom spacer selected from optionally substituted C1-C6 aliphatic and optionally substituted C1-C6 heteroaliphatic. In certain such embodiments, Y is a 1-4 atom spacer selected from optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C2-C6 heteroaHcenyl.
In certain embodiments, Y is a 1-4 atom spacer comprising a ring. In certain such embodiments, Y is selected from optionally substituted phenyl, optionally substituted monocyclic heteroaryl, optionally substituted C3-CS heterocycle, and optionally substituted alicyclic, including, but not limited to, optionally substituted cycloalkyl and optionally substituted cycloalkenyl.
In certain embodiments, Y is a 2-6 atom spacer comprising both (1) a ring selected from optionally substituted phenyl, optionally substituted monocyclic heteroaryl, optionally substituted C3-CS heterocycle, and optionally substituted alicyclic and (2) 1-4 atoms selected from optionally substituted C1-C6 aliphatic, and optionally substituted C1-C6 heteroaliphatic.
In certain embodiments, Y is not -N=CR6- orientated to form the dihydropyrazole. Thus, in such embodiments, the ring that includes Y cannot be:
In certain embodiments, Y is selected from:

(Figure Removed)
In certain embodiments, Q is selected from O and S. In certain embodiments, X is selected from O, S, NR10, and CR10R10; In certain embodiments, Z is a 1 to 5 atom spacer. In certain embodiments, Z is a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl and an optionally substituted C1-C6 heteroaryl. la certain embodiments, Z is a 1-5 atom spacer selected from an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C2-C6 alkenyl, an optionally substituted C2-C6 heteroalkenyl, an optionally substituted C2-C6haloalkenyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 heteroalkyl.
In certain embodiments, m is 0,1, or 2.
In certain embodiments, n is 0 or 1. In embodiments in which n is 0, R1 binds directly to Z and Rz and/or RJ are null, as appropriate. For example, if Z is a phenyl ring and n is 0, then R' binds directly to the phenyl ring and both R2 andR1 ate null.
In embodiments in which two or more of a particular group are present, the identities of those two or more particular groups are selected independently and, thus, may be the same or different from one another. For example, certain compounds of the invention comprise two or more R14 groups. The identities of those two or more R14 groups are each selected independently. Thus, .in certain embodiments, those R14 groups are all the same as one another; in certain embodiments, those Rw groups are all different from one another, and in certain embodiments, some of those R14 groups are the same as one another and some are different from one another. This independent selection applies to any group that is present in a compound more than once.
One of ordinary skill in the art will recognize that the complete lists of possible identities for each above-listed group (all R groups, Y, Q, Z, m, and n) may be narrowed to provide shorter lists of possible identities. For example, since in certain embodiments R1 is selected from hydrogen, CO2R.W, CONR'°R", SO2R10, and a carboxylic acid bioisostere, it is to be understood that in certain embodiments, R1 may be selected from COjR10, CONR"R11, and SO3R10, because each of those possible identities is included on the longer list of possible identities. One of ordinary skill in the art will also recognize that broader terms include combinations of narrower terms, which may be substituted and selected. For example, in certain embodiments, R2 is selected from an
optionally substituted C1-C4 aliphatic. Because aliphatics include, but are not limited to, alkyls and alkenes, in certain embodiments, R2 may be selected from an optionally substituted C1-C4 alkyl and an optionally substituted C1-C4 alkenyl. Similarly, in certain embodiments, R3 is selected from an optionally substituted C2-C3 alkyl and an optionally substituted C2-C4 alkenyl, because those alkyls and alkenyls are included in the definition of C1-C4 aliphatics.
One of ordinary skill in the art will also understand that the above listed groups may be selected in any combination. For example, in certain embodiments, R1 is selected from hydrogen, CO2R10, CONR10R!1, S03R10, and a carboxylic acid bioisostere; and R2 is selected from hydrogen, OR12, NRUR13, an optionally substituted C1-C4 aliphatic, an optionally substituted C1-C4 haloaliphatic, an optionally substituted C1-C4 heteroaliphatic, (CH2)mR14, an optionally substituted ring, and null. Therefore, in certain embodiments, R1 may be selected from hydrogen, and CO2R10; and at the same time R2 may be selected from hydrogen, OR12, NR12R13, and an optionally substituted C1-C4 aliphatic, because those lists of possible identities are included within the previous lists of possible identities. Such selection of combinations are included for all groups herein.
In certain embodiments, a compound of Formula I, n, or m is a selective TPO modulator. In certain embodiments, a compound of Formula I, n, or in is a selective TPO receptor agonist. In certain embodiments, a compound of Formula I, II, or III is a selective TPO receptor antagonist. In certain embodiments, a compound of Formula I, n, or III is a selective TPO receptor partial agonist. In certain embodiments, a compound of Formula I, II, or III is a tissue-specific selective TPO modulator. In certain embodiments, a compound of Formula I, n, or III is a selective TPO receptor binding compound. In certain embodiments, a compound of Formula I, II, or III is a TPO mimic.
In certain embodiments, the invention provides compounds including, but not limited to:
3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-l,2-dihydfo-mdol-3-ylidene]-hydrazmo}-2'-hydroxy-biphenyl-3 -carboxylic acid (Compound 101);
2'-Hydroxy-3'-{N'-[2-oxo-l-(4-propyl-phenyl)-l,2-dihydro-indol-3-yliden.e]-hydrazino}-biphenyl-3-carboxylic acid (Compound 102);
2l-Hydroxy-3l-{N'-[2-oxo-l-(4-ethyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 103);
2'-Hydroxy-3l-{Nl-[2-oxo-l-(4-trifluoromethoxy-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 104);
3'-{N'-[l-(3-Fluoro-4-methoxy-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 105);

3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-l,2-dtriydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-4-carboxylic acid (Compound 106);
2'-Hydroxy-3'-{N'-[2-oxo-l-(4-propyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-4-carboxylic acid (Compound 107);
2'-Hydroxy-3'- (N'-[2-oxo-1 -(4-ethyl-phenyl)-l ,2-dihydro-indol-3 -ylidene] -hydrazino} -biphenyl-4-carboxylic acid (Compound 108);
3'-{N'-[l-(4-tert-Butyl-phenyl)-2-oxo-l,2-dihydTo-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 109);
2'-Hydroxy-3'-{N'-[2-oxo-l-(4-trifluoromethyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 110);
3'-[N'-(l-Benzyl-5-chloro-2-oxo-l,2-dihydro-iTidol-3-ylidene)-hydrazino]-2l-hydroxy-biphenyl-3-carboxylic acid (Compound 111);
3'-[N'-( 1 -Benzyl-5-methyl-2-oxo-l ,2-dihydro-indol-3-ylidene)-hydrazino]-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 112);
3 '-[N'-( 1 -Benzyl-2-oxo-1,2-dihydro-indol-3 -ylidene)-hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 113);
2'-Hydroxy-3'-{N'-[2-oxo-l-(4-trifluoromethyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-4-carboxylic acid (Compound 114);
3'-{Nl-[l-(3)4-Dichloro-phenyl)-2-oxo-l)2-dihydro-indol-3-ylidene]-hydrazmo}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 115);
2'-Hydroxy-3l-{Nl-[l-(4-methyl-3-trifluoromethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 116);
S'-IN'-tl-tS-Fluoro-trifluoromethyl-phenyO-oxo-l-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 117);
3'-{N'-[l-(3,5-Bis-trifluoromethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazhio}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 11 8);
3l-{N'-[3-(3,4-Dimethyl-phenyl)-4-oxo-2-thioxo-tiiiazolidin-5-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 119);
2'-Hydroxy-3l-{N'-[l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydra2ino}-biphenyl-3-carboxylic acid (Compound 120);
3'- {N'-[l-(2-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-l ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 121);
3'- (N1- [ 1 -(2-Fluoro-4-methyl-phenyl)-2-oxo-1,2-dihydro-indol-3 -ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 122);

3'-{N'-[l-(4-Chloro-3-trifluoromethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 123);
3'-{N'-[l-(4-Butyl-pheny])-2-oxo-l,2-dihydro-indol-3-ylidene]-h.ydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 124);
3'- {N'-[ 1 -(3-Fluoro-phenyl)-2-oxo-l ,2-dihydro-indol-3-ylidene]-Jtydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 125);
2'-Hydroxy-3l-[N'-(2-oxo-l-m-tolyl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 126);
3'-{N'-[l-(4-Fluoro-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-liydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 127);
3l-[N'-(l-Benzyl-5-methoxy-2-oxo-l,2-dihydro-indol-3-ylidene)-hydrazino]-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 128);
2'-Hydroxy-3'-{N'-[2-oxo-l-(3-trifluoromethyl-phenyl)-l(2-dihy 3'-{N'-[5-Chloro-l-(4-isopropyl-pheaiyl)-2-oxo-l,2-dihydro-indc>l-3-yUdene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 130);
3'- {N'-[6-Chloro-1 -(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3 -ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 131);
3l-{Nl-[5-Fluoro-l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 132);
3'- {N'-[5 -Methoxy-1 -(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-irxdol-3 -ylidene]-hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 133);
3'-{N1-[l-(3,4-Dimethyl-phenyl)-5-fluoro-2-oxo-l,2-dihydro-incaol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 134) ;
3'-{N'-[l-(4-Fluoro-3-trifluoromethyl-phenyl)-5-fluoro-2-oxo-lJ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound, 135) ;
3'-{Nl-[l-(3,5-Dichloro-phenyl)-5-fluoro-2-oxo-l,2-dihydro-md.ol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 136) ;
31-{N'-[l-(4-Propyl-phenyl)-6-chloro-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazmo}-2t-hydroxy-biphenyl-3-carboxylic acid (Compound 137); and
a pharmaceutically acceptable salt, ester, amide, or prodrug of any of those compounds. In certain embodiments, such compounds are selective TPO modulators.
In certain embodiments, the invention provides compounds including, but not limited to:

(±)-2'-Hydroxy-3'-(N'- {2-oxo- 1 -[4-(2,2,2-trifluoro-l -hydroxy-ethyl)-phenyl]- 1 ,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 138);
(±)-2'-Hydroxy-3'-(N-{2-oxo-l-[4-(2,2,2-trifluoro-l-methoxy-ethyl)-phenyl]-l)2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 139);
2'-Hydroxy-3l-(N-{2-oxo-l-[4-(2,2,2-trifluoro-ethyl)-phenyl]-l)2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 140);
hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 141);
3 '- {AP-[ 1 -(3 ,4-Dimethyl-phenyl)-5 -fluoro-4-methyl-2-oxo-l ,2-dihydro-indol-3 -ylidenej-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 142);
hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 143);
5.(4.{A^-[l-(334-pimethyl-phenyl)-2-oxo-6-trifluoromethyI-l,2-dihydro-indol-3-ylidene]-hydrazino} -3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 144);
5-(4.{[l-(3j4-Dimethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 145);
3'-{JV-[l-(3,4-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-l,2-dihydro-mdol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 146);
3'-{[4-Oiloro43,4-dimel-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 147);
5-(4-{Ar-[l-(3,4-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 148);
5-(4-{A-[4-Chloro-l-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 149);
3-(4-{A'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-phenyl)-acrylic acid (Compound 150);
l-(3,4-Dimemyl-phenyl)-3-{[2-hydroxy-4-(4-oxo-2-tiiioxo-thiazolidin-5-ylidenemethyl)-phenyl]-hydrazono}-6-trifluoromethyl-l,3-dihydro-indol-2-one (Compound 151);
l-(3,4-Dimeihyl-phenyl)-4-fluoro-3-{[2-hydroxy-4-(4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-phenyl]-hydrazono}-6-trifluoromethyl-l,3-dihydro-indol-2-one (Compound 152);
5K3-{^/'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-lJ2-dihydro-indol-3-ylidene]-hydrazino}-2-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 153);
3'-{N'-[5-Chloro-2-oxo-l-(4-propyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-2t-hydroxy-biphenyl-3-carboxylic acid (Compound 154);

21-Hydroxy-3'-{N'-[l-(4-methylsulfanyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 155);
2'-Hydroxy-3'-{N'-[l-(4-Tnethoxymethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 156);
(±)-2'-Hydroxy-3'-(NI- {2-oxo-l -[4-(2,2,2-trifluoro-l -hydroxy-1 -methyl-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 157);
3'- {N'-[5 -Fluoro-1 -(4-methyl-3-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 158);
2'-Hydroxy-3'-(Nl-{2-oxo-l-[4-2,2,2-trifluoro-l-methoxy-l-methyl-ethyl)-phenyl]-l,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 159);
3'- {N'-[ 1 -(3,4-Dimethyl-phenyl)-6-fluoro-2-oxo-l ,2-dihydro-indol-3 -ylidene]-hydrazino }-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 160);
3'-{N'-[6-Fluoro-l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 161);
3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-5-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 162);
3'-{Nl-[6-Fluoro-2-oxo-l-(4-propyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 163);
Z'-Hydroxy-S'-IN'-p-oxo-l^-propyl-phenyO-S-trifluoromethyl-l^-dihydro-indol-S-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 164);
3'-{N'-[4,5-Difluoro-l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-mdol-3-ylidene]-hydrazinoJ^'-hydroxy-biphenyl-S-carboxylic acid (Compound 165);
2l-Hydroxy-3l-[Nl-(2-oxo-l-piperidin-4-yl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 166);
S'-IN'-tS-Fluoro-l^-fluoro^-methyl-phenyO^-oxo-l^-dihydro-indol-S-ylidene]-hydrazmo}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 167);
2l-Hydroxy-3'-pSr-(l-methyl-2-oxo-lJ2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 168);
S'-fN'-fl-Cyclopentyl^-oxo-l^-dihydro-indol-S-ylideneJ-hydrazinol^'-hydroxy-biphenyl-3-carboxylic acid (Compound 169);
S'-fN'-llS-Dimethyl-phenyli-e-methyl-oxo-l-dihydro-indol-S-ylidenel-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 170);
2'-Hydroxy-3'-[Nl-(2-oxo-l-phenyl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 171);

3 '-[N'-(6-Fluoro-2-oxo- 1 -phenyl-2,3 -dihrydro- 1 H-indol-3-y l)-hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 172);
3'- {N'-[ 1 -(3 ,4-Dimethyl-phenyl)-6-isopropyl-2-oxo- 1 ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 173);
3'-{Nl-[l-(3,4-Dimethyl-phenyl)-4-isopropyl-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazmo}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 174);
3'-{N1-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2'-hydroxy-biphenyl-3-cartoxylic acid (Compound 175);
S'-Chloro-S'-IN'lS-dimethyl-pheny-Z-oxo-e-trifluoromethyl-l^-dihydro-indol-S-ylidene]-hydrazino}-4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 176);
3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-6-fluoro-2'-hydroxy-biphenyl-3-cartooxylic acid (Compound 177);
hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 178);
3'-{N'-[l-(3,4-Diniethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-3-methyl-biphenyl4-carboxylic acid (Compound 179);
3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-2,3-dihydro-lH-indol-3-yl3-hydrazino}-2-fluoro-2'-hydroxy-biphenyl4-carboxylic acid (Compound 180);
yl]-hydrazino}-4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 181);
mdol-3-ylidene]-hydrazino}-4-fluoro-2'-hydrox.y-biphenyl-3-carboxylic acid (Compound 182);
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-l-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-lH-indole-6-carboxylic acid methyl ester (Compound 183);
3-[(3 '-Carboxy-4'-fluoro-2-hydroxy-biplienyl-3 -yl)-hydrazono] - 1 -(3 ,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-lH-indole-6-carboxylic acid methyl ester (Compound 184);
3-[(3l-Carboxy-4l-fluoro-2-hydroxy-biphenyl-3-yl)-hydrazono]-l-(3,4-dimethyl-phenyl)-2-oxo-2,3-dihydro-lH-indole-6-carboxylic acid methyl ester (Compound 185);
3-[(3l-Carboxy-5-chloro-4l-fluoro-2-hydroxy-biphenyl-3-yl)-hydrazono]-l-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-lH-indole-6-carbox.ylic acid methyl ester (Compound 186);
3l-{N'-[l-(2-Cyano-thiophen-3-yl)-2-ox.o-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 187);
2'-Hydroxy-3'-[Nl-(2-oxo-l-thiophen-3-yl-l)2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 188);

3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-l-(3,4-dimethyl-phenyl)-2-oxo-2,3-dihydro-lH-indole-6-carboxylic acid methyl ester (Compound 189);
3'-{N'-[l-(4-Chloro-3-trifluoromethyl-phenyl)-6-cyano-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 190);
5'-Chloro-3l-{N'-[6-cyano-l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 191);
3 '- {N1- [6-Cyano- 1 -(4-isopropyl-phenyl)-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino } -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 192);
(±)-l-(3,4-Dimethyl-phenyl)-3-{[2-hydroxy-3'-(2,2,2-trifluoro-l-hydroxy-ethyl)-biphenyl-3-yl]-hydrazono } -6-methanesulfonyl- 1 ,3 -dihydro-indol-2-one (Compound 1 93);
3 '- {N'-[6-Cyano- 1 -(4-isopropyl-phenyl)-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 194);
3'-{N'-[l-(3,4-Dimethyl-phenyl)-5-nitro-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 195);
3l-{N'-[l-(3s4-Dimethyl-phenyl)-6-methanesulfonyl-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2l-hydroxy-biphenyl-3-carboxylic acid (Compound 196);
S'-fN'-te-Cyano-lS-dimethyl-phenylJoxo-l-dihydro-indol-S-ylidenej-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 197);
hydroxy-biphenyl-3-carboxylic acid (Compound 198);
3l-[N'-(l-Furan-3-yl-2-oxo-l,2-dihydro-indol-3-ylidene)-hydrazino]-2l-hydroxy-biphenyl-3-carboxylic acid (Compound 199);
3'-[N'-( l-Benzo[l ,3]dioxol-5-yl-2-oxo-l ,2-dihydro-indol-3-ylidene)-hydrazino]-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 200);
2'-Hydroxy-3'-{Nl-[l-(3-methyl-thiophen-2-yl)-2-oxo-l>2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 201);
21-Hydroxy-3l-[NI-(2-oxo-l-thiophen-2-yl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 202);
2'-Hydroxy-3l-{N'-[l-(4-isopropyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 203);
2'-Hydroxy-3'-{Nl-[2-oxo-l-(4-propyl-phenyl)-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 204);
3'-{N'-[l-(4-Ethyl-phenyl)-5)7-difluoro-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-21-hydroxy-biphenyl-3-carboxylic acid (Compound 205);

3'- {N'-[ 1 -(3 ,4-Dimethyl-phenyl)-5 ,7-difluoro-2-oxo-l ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 206);
3'- {N'-[5 ,7-Difluoro-2-oxo- 1 -(4-propyl-phenyl)- 1 ,2-dihydro-indol-3 -ylidene] -hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 207);
3'-{N'-[5,7-Difluoro-l-(4-isopropyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 208);
3'-{N'-[l-(3,4-Dime%l-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 209);
3'.{N1-[l-(3,4-Dimethylrphenyl)-6-ethyl-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 210);
3'- {N'-[ 1 -(3 ,4-Dimethyl-phenyl)-6-methoxy-2 -oxo-1 ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 211);
3'-{N'-[5-Chloro-l-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 212);
3'- (N'-[l -(3,4-Dimethyl-phenyl)-6,7-dimethyl-2-oxo-l ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 213);
2-3'-{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l)2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-4-yl)-2-methyl-propionic acid (Compound 214);
(-)-2-(3I-{Nl-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-4-yl)-propionic acid (Compound 215) and (+)-2-(3'-{N-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene3-hydrazino}-2'-hydroxy-biphenyl-4-yl)-propionic acid (Compound 215a);
(±)-(3 '- {N'-[ 1 -(3 ,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl- 1 ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-5'-methyl-biphenyl-4-yl)-propionic acid (Compound 216);
(±)-2-(3l-{N'-[l-(3)4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3- ylidenel-hydrazinoJ-S'-fluoro'-hydroxy-biphenyM-ylJ-propionic acid (Compound 217);
5-(4-{N'-[l-(3)4-Dimethyl-phenyl)-5,7-difluoro-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 218);
5-(4- {N'-[ 1 -(4-Ethyl-phenyl)-5 ,7-difluoro-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino } -3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 219);
5-(4-{Nl-[5,7-Difluoro-2-oxo-l-(4-propyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino} -3 -hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 220);
ylidene]-hydrazino}-benzylidene)-thiazolidine-2,4-dione (Compound 221);

5-(3-Hydroxy-4-{N'-[l-(4-isopropyl-phenyl)-2-oxo-5,7-difluoro-l,2-dihydro-indol-3-ylidene]-hydrazino}-benzylidene)-thiazolidine-2,4-dione (Compound 222);
3 '- {N'-[ 1 -(3 ,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl- 1 ,2-dihydro-indol-3 -y lidenej-hydrazino) -5'-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 223);
5'-Chloro-3'-{N'-[l-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 224);
3'-{Nr-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-5'-methyl-biphenyl-3-carboxylic acid (Compound 225);
2l-Hydroxy-3l-{N'-[2-oxo-6-trifluoromethyl-l-(4-trifluoromethyl-phenyl)-lJ2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 226);
3'-{N'-[l-(4-Ethyl-3-methyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 227);
3'-{Nl-[l-(4-Chloro-3-trifluoromethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 228);
SN'-fS.S-Diinethyl-phenyO-oxo-e-trifluoromethyl-l-dihydro-indol-S-ylidene]-hydrazino}-5'-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 229);
hydrazino}-4,5'-difluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 230);
S'-IN'-tlS.S-Dimethyl-phenyli-oxo-e-trifluoromethyl-l-dihydro-indol-S-ylidene]-hydrazinoJ^.S'-difluoro-Z'-hydroxy-biphenyl-S-carboxylic acid (Compound 23 1);
4,5'-Difluoro-2'-hya^oxy-3'-{N'-[2-oxo-6-trifluoromethyl-l-(4-trifluoromethyl-phenyl)-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 232);
3'-{N'-[l-(4-Fluoro-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylideneJ-hydrazinoJ^'-hydroxy-biphenyl-S-carboxylic acid (Compound 233);
2'-Hydroxy-3l-{Nl-[l-(4-methoxy-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 234);
31-{N(-[l-(4-Fluoro-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazinoJ^'-hydroxy-biphenyl-S-carboxylic acid (Compound 235);
3 - {N'-[ 1 -(3 ,5 -Dimethoxy-phenyl)-2-oxo-6-trifluoromethyl-l ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 236);
3 '- {N'-[ 1 -(3-Dimethoxy-phenyO-oxo-e-trifluoromethyl-l ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 237);
S'-tN'-tlS.S-Difluoro-phenylJ^-oxo-e-trifluoromethyl-l^-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 238);

5'-Fluoro-3 '- {N'-[ 1 -(4-fluoro-3 ,5 -dimethyl-phenyl)-2-oxo-6-trifluoromethyl- 1 ,2-dihydro-indol-3-ylidene]4iydrazmo}-2'4iydroxy-biprienyl-3-carboxylic acid (Compound 239);
4,5'-Difluoro-31-{Nl-[l-(4-fluoro-3,5-dimethyl-phenyr)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 240);
2'-Hydroxy-3'-{N'-[l-(4-methoxy-3,5-dimethyl-phenyl)-2-oxo-6-trifluoroine1hyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 241);
2l-Hydroxy-3'-{N'-[l-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid (Compound 242);
3'-{N'-[l-(4-Cyclohexyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 243);
2'-Hydroxy-3l-[N'-(2-oxo-l-pyridin-2-yl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 244);
2'-Hydroxy-3'-[N'-(2-oxo-l-pyridin-3-yl-l,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid (Compound 245);
31-{N1-[l-(4-Ethyl-phenyl)-2-oxo-6-trifluoroniethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 246);
3l-{N'-[l-(4-Ethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 247);
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-l-(3>5-dimethyl-phenyl)-2-oxo-2,3-dihydro-l-H-indole-5-carboxylic acid methyl ester (Compound 248);
3'-{N'-[l-(3-CMorcHt-methyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 249);
5-(4-{Nl-[l-(3,5-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-l)2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-benzylidene)-thiazolidine-2,4-dione (Compound 250);
2l-Hydroxy-3'-(N1-{2-oxo-l-[4-(4,4,4-trifluoro-butyl)-phenyl]-l)2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid (Compound 251);
ylideneJ-hydrazmoJ^'-hydroxy-biphenyl-S-carboxylic acid (Compound 252);
3'-{N'-[l-(4-tert-Butyl-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 253);
S'-fN'-tl-Dimethyl-phenyO-oxo-e-trifluoromethyl-l-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-4-carboxylic acid (Compound 254);
3 '- {N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-bromo-l ,2-dihydro-indol-3-ylidene]-hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 255);

3 '- {N1- [ 1 -(3 ,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl- 1 ,2-dihydro~indol-3 -yli dene]-hydrazino}-3-fluoro-2'-hydroxy-biphenyl-4-carboxylic acid (Compound 256);
3'- {N'-[ 1 -(3,5-Bis-trifluoromethyl-phenyl)-2-oxo-6-trifluoromethyl-l ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compoimd 257);
3'.{N'-[i-(3s4-Dichloro-phenyl)-2-oxo-6-trifluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 258);
S'-fN'-tlKS.S-Dichloro-phenylJ-oxo-e-trifluoromethyl-l^-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 259);
3_(4- {N'-[l -(3 ,5 -Dimethyl-phenyl)-2-oxo-6-trifluoromethyl- 1 ,2-dihydro-indol-3 -ylidene] -hydrazino}-3-hydroxy-phenyl)-2-methyl-acrylic acid (Compound 260);
3.(4.{N'-[l-(3,4-Dimethyl-phenyl)-2-oxo-6-trtfluoromethyl-l,2-dihydro-indol-3-ylidene]-hydrazino}-3-hydroxy-phenyl)-2-methyl-acrylic acid (Compound 261);
2'-Hydroxy-3'-[N'-(2-oxo-7-phenyl-l,2-dihydro-indol-3-ylidene)-hydrazmo]-bip]nienyl-3-carboxylic acid (Compound 262);
S'-IN'-tl-CS-Dimethyl-phenyO-oxo-e-trifluoromethoxy-l-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 263);
3'-{N1-[l-(3)4-Dimethyl-phenyl)-2-oxo-6-(l,l,2,2-tetrafluoro-ethoxy)-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 264);
3'-{N'-Il3,4-Dimethyl-phenyl)-5-methyl-2-oxo4,2-dihydro-mdol-3-ylidene]-h.ydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 265);
3 '- {N'-[ 1 -(4-Isopropyl-phenyl)-5-methyl-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 266);
2'4iydroxy-biphenyl-3-carboxylic acid (Compound 267);
3'-{N'-[l-(3-Trifluoromethyl-phenyl)-6-trifluoromethyl-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 268);
3'- {N'-[ 1 -(4-Trifluoromethoxy-phenyl)-5 -trifluoromethoxy-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 269);
S'-fN'-tlS.S-Dimethyl-phenyO-e-trifluoromethyl-oxo-l-dihydro-indol-S-ylidene]-hydrazinoJ^'-hydroxy-biphenyl-S-carboxylic acid (Compound 270);
S'-IN'-tl-CS-Trifluoromethyl-phenyOe-dimethyl-oxo-l-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 271);
S'-IN'-flS-Trifluoromethyl-phenyO-S.e-dimethy-oxo-l-dihydro-indol-S-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 272);

3'- {N'-[ 1 -(3 ,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo- 1 ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-5'-chloro-4-fluoro-biphenyl-3-carboxylic acid (Compound 273);
3'- {N'-[ 1 -(3 ,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo- 1 ,2-dihydro-indol-3 -ylidene]-hydrazino}-2'-hydroxy-4-fluoro-biphenyl-3-carboxylic acid (Compound 274);
3 '- { JV- [6-Chloro-l -(3 ,4-dimethyl-phenyl)-2-oxo-l ,2-dihydro-indol-3 -ylidene]-hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 275);
3 '- {W-[5-Fluoro-2-oxo- 1 -(4-propyl-phenyl)- 1 ,2-dihydro-indol-3 -ylidene] -hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 276);
3 '- {AP-[5 -Cyano- 1 -(3 ,4-dimethyl-phenyl)-2-oxo-l ,2-dihydro-indol-3 -ylidene] -hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 277);
3'-{A-[6-Chloro-l-(3,5-dimethyl-phenyl)-2-oxo-l,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 278);
4-Fluoro-3'- {W-[ 1 -(3 -fluoro-4-methyl-phenyl)-2-oxo-6-trifluorometh.yl- 1 ,2-dihydro-indol-3-ylidene]-hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 279); and
a pharmaceutically acceptable salt ester, amide or prodrug of any of those compounds.
In certain embodiments, the invention provides compounds including, but not limited to:
3'-{N'-[l-(4-Chloro-3,5-dimethylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 280);
3'-{N'-[l-(3,5-Dimethylphenyl)-4-fluoro-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-2'-hydroxybiphenyl-4-fluoro-3-carboxylic acid (Compound 281);
3'-{N'-[l-Benzo[l,3]dioxo-5-yl-2-oxo-6-1rifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 282);
3l-{NI-[l-Benzo[l,3]dioxo-5-yl-2-oxo-6-trifluoromethyl-l>2-dihydroindol-3-ylidene]hydrazino}-2'-hydroxybiphenyl-2-fluoro-3-carboxylic acid (Compound 283);
ylidene]hydrazino}-2'-hydroxybiphenyl-2-hydroxy-3-carboxylic acid (Compound 284);
3'-{NI-[l-(3-Methoxycarbonylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 285);
3'-{Nl-[l-(3-Methoxycarbonylphenyl)-2-oxo-l12-dihydromdol-3-yli 3l-{A-[7-Aza-l-(3,4-dimethylphenyl)-2-oxo-l,2-dihydroindol-3-ylidene]hydrazino}-21-hydroxybiphenyl-3-carboxylic acid (Compound 287);
3l-{NI-[l-(3,5-Dimethylphenyl)-2-oxo-l,2-dihydroindol-6-trifluorornethyl-3-ylidene]hydrazino}-2'-hydroxybiphenyl-3-(2-methyl-2-propionic acid) (Compound 288);

3 '- {N'-[ 1 ,3 -N,N-Dimethylbarbitur-5 -ylidenejhydrazino} -2'-hydroxybiphenyl-3 -carboxylic acid (Compound 289);
3l-{Nl-[l-N-(4-Trifluoromethylbenzyl)-2,8-dioxo-l,2,7,8-tetrahydroisoquinolin-7-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 290);
3l-{N'-[l-N-(4-Methylbenzyl)-2,8-dioxo-l,2,7J8-tetrahydroisoquinolin-7-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 291);
hydroxybiphenyl-3-carboxylic acid (Compound 292);
3'-{N'-[l-N-(4-Trifluoromethylphenyl)-2,8-dioxo-l,2,7,8-tetrahydroisoquinolin-7-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 293);
3'. {N'-[ 1 -N-(3-Trifluoromethylphenyl)-2,8-dioxo- 1 ,2,7,8-tetrahydroisoquinolin-7-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid (Compound 294);
3'_{N'.[i.N-(3,5-Dimethylphenyl)-2,8-dioxo-l,2,7,8-tetrahydroisoquinolin-7-ylidene]hydrazmo}-2'-hydroxybiphenyl-3 -carboxylic acid (Compound 295);
hydroxybiphenyl-3-carboxylic acid (Compound 296);
3'-{N'-[l-N-(3,4-Dimethylphenyl)-2)8-dioxo-l,2,7,8-tetrahydroisoquinolin-7-ylidene]hydrazino}-2'-hydroxybiphenyl-3 -carboxylic acid (Compound 297);
ylidene3hydrazino}-2'-fluorobiphenyl-3-carboxylic acid (Compound 298); SKS-IN'-Cl-NS-Dimethylpheny^^-oxo-e-trifluoromethyl-l^-ylidene]hydrazino}-2-hydroxyphenyl)-2(Z)-propenoic acid (Compound 299);
ylidene]hydrazino}-2-hydroxyphenyl)-2(Z)-propenoic acid (Compound 300);
5-3-{N'-[l-(3,4-Dimemylphenyl)-2-oxo-4-fluoro-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-2-hydroxybenzylidene)thiazolidine-2,4-dione (Compound 301);
2-Chloro-3-(4- {N'-[l -(3 ,4-dimethylphenyl)-2-oxo-6-trifluoromethyl-l ,2-dihydroindol-3 -ylidene]hydrazino}-3-hydroxyphenyl)-2-propenoic acid (Compound 302);
2-Ethyl-3-(4-{N'-[l-(3)4-dimethylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-3-hydroxyphenyl)-2-propenoic acid (Compound 303);
ylidene]hydrazino}-3-hydroxyben2ylidene)-l,3-diazolidine-2,4-dione (Compound 304);
S-IN'-tl-tS-Dimethylphenyli-oxo-e-trifluoromethyl-dihydroindol-S-
ylidene]hydrazino} -3 -hydroxybenzylidene)-! ,3 -diazolidine-2,4-dione (Compound 305);

2-Fluoro-3-(4-{N'-[l-(3,4-dimethylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-3-hydroxyphenyl)-2-propenoic acid (Compound 306);
(±)-2-Methoxy-3-(4-{N'-[l-(3,5-dimethylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-3-hydroxyphenyl)propanoic acid (Compound 307);
4-(3 - {N'-[ 1 -(3,4-dimethylphenyl)-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2-hydroxyphenyl)butanoic acid (Compound 308);
3-(2-{N'-[l-(3,5-dimethylphenyl)-2-oxo-6-trifluoromethyl-l,2-dihydroindol-3-ylidene]hydrazino}-3-hydroxyphenoxy)propanoic acid (Compound 309);
4-(4- (N'-[ 1 -(3,4-dimethylphenyl)-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-3-hydroxyphenyl)butanoic acid (Compound 310); and a pharmaceutically acceptable salt ester, amide or prodrug of any of those compounds.
In certain embodiments, the present invention provides any single compound selected from any of the above lists of compounds. In certain embodiments, the present invention provides any number and any combination of compounds selected from the above lists of compounds.
Certain compounds of the present inventions may exist as stereoisomers including optical isomers. The present disclosure is intended to include all stereoisomers and both the racemic mixtures of such stereoisomers as well as the individual enantiomers that may be separated according to methods that are known in the art or that may be excluded by synthesis schemes known in the art designed to yield predominantly one enantomer relative to another.

Certain Synthesis Methods
In certain embodiments, certain compounds of the present invention can by synthesized using the following Schemes.

(Figure Removed)
The process of Scheme I is a multi-step synthetic sequence that commences with the palladium catalyzed cross-coupling of a phenylboronic acid such as structure 2 and an aryl bromide such as structure 1 to form the biaryl structure 3. Deprotection of the methyl ether is followed by nitration and hydrogenation to give the biphenyl amino acid such as structure 4. The amino group is then diazotized under standard conditions and is treated with the appropriate coupling partner to give the final product of structure 6.
(Figure Removed)
The process of Scheme n is a multi-step synthetic sequence that commences with the copper catalyzed cross-coupling of an oxindole such as structure 7 and an aryl or alkyl bromide to provide an N-substituted oxindole of structure 8. This is then followed by coupling the N-substituted oxindole with the diazonium salt of the biphenyl amino acid such as structure 4 to give the final product of structure 9.
(Figure Removed)
The process of Scheme III is a multi-step synthetic sequence that commences with the reductive amination of an aniline such as structure 10 with a benzaldehyde and conversion into the chloroacetanilide of structure 11 with chloroacetyl chloride. Palladium catalyzed ring closure gives the N-benzyl oxindole such as structure 12, which is then coupled to the diazonium salt of the biphenyl amino acid of structure 4 to give the final product of structure 9.
(Figure Removed)
The process of Scheme IV is a multi-step synthetic sequence that commences with the conversion of an amine of structure 13 into an N-aryl rhodanine of structure 14 with bis(carboxymethyl) trithiocarbonate. The rhodanine is then coupled to the diazonium salt of the biphenyl amino acid such as structure 4 to give the final product of structure 15.
(Figure Removed)
In Scheme V, a hyrdoxynitrobenzaldehyde such as structure 16 is converted into either a cinnamate such as structure 17 or thiazolidinedione derivative of structure 19. The requisite nitro-group is reduced and then converted into a diazonium salt and coupled to the corresponding N-aryl oxindole of structure 8 to give the final compound of structure 20.
One of skill in the art will recognize that analogous synthesis schemes may be used to synthesize similar compounds. One of skill will recognize that compounds of the present invention may be synthesized using other synthesis schemes. In certain embodiments, the invention provides a salt corresponding to any of the compounds provided herein.
In certain embodiments, the invention provides a salt corresponding to a selective TPO modulator. In certain embodiments, the invention provides a salt corresponding to a selective TPO receptor binding agent. In certain embodiments, a salt is obtained by reacting a compound with an acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. In certain embodiments, a salt is obtained by reacting a compound with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or a potassium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of orgaoaic bases such as

choline, dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, 4-(2-hydroxyethyD-morpholine, l-(2-hydroxyethyl)-pyrrolidine, ethanolamine and salts with amino acids such as arginine, lysine, and the like. In certain embodiments, a salt is obtained by reacting a free acid form of a selective TPO modulator or selective TPO binding agent with multiple molar equivalents of a base, such as bis-sodium, bis-ethanolamine, and the like.
In certain embodiments, a salt corresponding to a compound of the present invention is selected from acetate, ammonium, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, cholinate, clavulanate, citrate, dihydrochloride, diphosphate, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabanine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mucate, napsylate, nitrate, N-methylglucamine, oxalate, pamoate (embonate), palmitate, pantothenate, phosphate, polygalacturonate, potassium, salicylate, sodium, stearate, subaceatate, succinate, sulfate, tannate, tartrate, teoclate, tosylate, triethiodide, tromethamine, trimethylammonium, and valerate salts.
In certain embodiments, one or more carbon atoms of a compound of the present invention are replaced with silicon. See e.g., WO 03/037905A1; Tacke and Zilch, Endeavour, New Series, 10,191-197 (1986); and Bains and Tacke, Curr. Opin. Drug Discov Devel. Jul:6(4):526-43(2003). In certain embodiments, compounds of the present invention comprising one or more silicon atoms possess certain desired properties, including, but not limited to, greater stability and/or longer half-life in a patient, when compared to the same compound in which none of the carbon atoms have been replaced with a silicon atom. Certain Assays
In certain embodiments, compounds of the present invention may be used in a any of a variety of assays. For example, compounds of the present invention may be tested for potency as selective TPO modulators in a luciferase assay,, such as those described in Lamb, et al., Nucleic Acids Research, 23: 3283-3289(1995) and/or Seidel et al., Proc. Nat. Acad. Sci. USA; 92: 3041-3045 (1995).
Certain compounds of the present invention may be used in in vitro proliferation and/or differentiation assays, such as those described by Bartley et al., Cell, 77: 1117-1124 (1994) and/or Cwirla, et al., Science, 276:1696-1699 (1997). Certain Pharmaceutical Compositions
In certain embodiments, at least one selective TPO modulator, or pharmaceutically acceptable salt, ester, amide, and/or prodrug thereof, combined with one or more pharmaceutically acceptable carriers, forms a pharmaceutical composition. Techniques for

formulation and administration of compounds of the present invention may be found for example, in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is prepared using known techniques, including, but not limited to mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tabletting processes.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is a liquid (e.g., a suspension, elixir and/or solution). In certain of such embodiments, a liquid pharmaceutical composition comprising one or more compounds of the present invention is prepared using ingredients known in the art, including, but not limited to, water, glycols, oils, alcohols, flavoring agents, preservatives, and coloring agents.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is a solid (e.g.t a powder, tablet, and/or capsule). In certain of such embodiments, a solid pharmaceutical composition comprising one or more compounds of the present invention is prepared using ingredients known in the art, including, but not limited to, starches, sugars, diluents, granulating agents, lubricants, binders, and disintegrating agents.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is formulated as a depot preparation. Certain such depot preparations are typically longer acting than non-depot preparations. In certain embodiments, such preparations are administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. In certain embodiments, depot preparations are prepared using suitable polymeric or hydrophobic materials (for example an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention comprises a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. Certain delivery systems are useful for preparing certain pharmaceutical compositions including those comprising hydrophobic compounds. In certain embodiments, certain organic solvents such as dimethylsulfoxide are used.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention comprises one or more tissue-specific delivery molecules designed to deliver the one or more compounds of the present invention to specific tissues or cell types. For example, in certain embodiments, pharmaceutical compositions include liposomes coated with a tissue-specific antibody.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention comprises a co-solvent system. Certain of such co-solvent

systems comprise, for example, benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. In certain embodiments, such co-solvent systems are used for hydrophobic compounds. A non-limiting example of such a co-solvent system is the VPD co-solvent system, which is a solution of absolute ethanol comprising 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant Polysorbate 80™ , and 65% w/v polyethylene glycol 300. The proportions of such co-solvent systems may be varied considerably without significantly altering their solubility and toxicity characteristics. Furthermore, the identity of co-solvent components may be varied: for example, other surfactants may be used instead of Polysorbate 80™; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose.
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention comprises a sustained-release system. A non-limiting example of such a sustained-release system is a semi-permeable matrix of solid hydrophobic polymers. In certain embodiments, sustained-release systems may, depending on their chemical nature, release compounds over a period of hours, days, weeks or months.
In certain embodiments, a pharmaceutical composition comprising a compound of the present invention is prepared for oral administration. In certain of such embodiments, a pharmaceutical composition is formulated by combining one or more compounds of the present invention with one or more pharmaceutically acceptable carriers. Certain of such carriers enable compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient. In certain embodiments, pharmaceutical compositions for oral use are obtained by mixing one or more compounds of the present invention and one or more solid excipient. Suitable excipients include, but are not limited to, fillers, such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In certain embodiments, such a mixture is optionally ground and auxiliaries are optionally added. In certain embodiments, pharmaceutical compositions are formed to obtain tablets or dragee cores. In certain embodiments, disintegrating agents (e.g., cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate) are added.
In certain embodiments, dragee cores are provided with coatings. In certain of such embodiments, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to tablets or dragee coatings.

In certain embodiments, pharmaceutical compositions for oral administration are push-fit capsules made of gelatin. Certain of such push-fit capsules comprise one or more compounds of the present invention in admixture with one or more filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In certain embodiments, pharmaceutical compositions for oral administration are soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. In certain soft capsules, one or more compounds of the present invention are be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added.
m certain embodiments, pharmaceutical compositions are prepared for buccal administration. Certain of such pharmaceutical compositions are tablets or lozenges formulated in conventional manner.
In certain embodiments, a pharmaceutical composition is prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, etc.). In certain of such embodiments, a pharmaceutical composition comprises a carrier and is forraxalated in aqueous solution, such as water or physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. In certain embodiments, other ingredients are included (e.g., ingredients that aid in solubility or serve as preservatives). In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents and the like. Certain pharmaceutical compositions for injection are presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Certain pharmaceutical compositions for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Certain solvents suitable for use in pharmaceutical compositions for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, and liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, such suspensions may also contain suitable stabilizers or agents that increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.
In certain embodiments, a pharmaceutical composition is prepared for transmucosal administration. In certain of such embodiments penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
In certain embodiments, a pharmaceutical composition is prepared for administration by inhalation. Certain of such pharmaceutical compositions for inhalation are prepared in the form of an aerosol spray in a pressurized pack or a nebulizer. Certain of such pharmaceutical compositions comprise a propellant, e.g., dichlorodifluoromethane,

trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In certain embodiments using a pressurized aerosol, the dosage unit may be determined with a valve that delivers a metered amount. In certain embodiments, capsules and cartridges for use in an inhaler or insufflator may be formulated. Certain of such formulations comprise a powder mixture of a compound of the invention and a suitable powder base such as lactose or starch.
In certain embodiments, a pharmaceutical composition is prepared for rectal administration, such as a suppositories or retention enema. Certain of such pharmaceutical compositions comprise known ingredients, such as coco a butter and/or other glycerides.
hi certain embodiments, a pharmaceutical composition is prepared for topical administration. Certain of such pharmaceutical compositions comprise bland moisturizing bases, such as ointments or creams. Exemplary suitable ointment bases include, but are not limited to, petrolatum, petrolatum plus volatile silicones, lanolin and water in oil emulsions such as Eucerin™, available from Beiersdorf (Cincinnati, Ohio). Exemplary suitable cream bases include, but are not limited to, Nivea™ Cream, available from Beiersdorf (Cincinnati, Ohio), cold cream (USP), Purpose Cream™, available from Johnson & Johnson (New Brunswick, New Jersey), hydrophilic ointment (USP) and Lubriderm™, available from Pfizer (Morris Plains, New Jersey).
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention comprises an active ingredient in a therapeutically effective amount. In certain embodiments, the therapeutically effective amount is sufficient to prevent, alleviate or ameliorate symptoms of a disease or to prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art.
In certain embodiments, one or more compounds of the present invention is formulated as a prodrug. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically more active form of the compound. In certain embodiments, prodrugs are useful because they are easier to administer than the corresponding active form. For example, in certain instances, a prodrug may be more bioavailable (e.g., through oral administration) than is the corresponding active form, hi certain instances, a prodrug may have improved solubility compared to the corresponding active form. hi certain embodiments, prodrugs are less water soluble ttian the corresponding active form. In certain instances, such prodrugs possess superior transmittal a.cross cell membranes, where water solubility is detrimental to mobility. In certain embodiments, a prodrug is an ester, hi certain such embodiments, the ester is metabolically hydrolyzed to carboxylic acid upon administration. In certain instances the carboxylic acid containing compound is the corresponding active form, hi

certain embodiments, a prodrug comprises a short peptide (polyaminoacid) bound to an acid group. In certain of such embodiments, the peptide is cleaved upon administration to form the corresponding active form.
In certain embodiments, a prodrug is produced by modifying a pharmaceutically active compound such that the active compound will be regenerated upon in vivo administration. The prodrug can be designed to alter the metabolic stability or the transport characteristics of a drug, to mask side effects or toxicity, to improve the flavor of a drug or to alter other characteristics or properties of a drug. By virtue of knowledge of pharmacodynamic processes and drug metabolism in vivo, those of skill in this art, once a pharmaceutically active compound is known, can design prodrugs of the compound (see, eg., Nogrady (1985) Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392).
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is useful for treating a conditions or disorders in a mammalian, and particularly in a human, patient. Suitable administration routes include, but are not limited to, oral, rectal, transmucosal, intestinal, enteral, topical, suppository, through inhalation, intrathecal, intraventricular, intraperitoneal, intranasal, intraocular and parenteral (e.g., intravenous, intramuscular, intramedullary, and subcutaneous). In certain embodiments, pharmaceutical intrathecals are administered to achieve local rather than systemic exposures. For example, pharmaceutical compositions may be injected directly in the area of desired effect (e.g., in the renal or cardiac area).
In certain embodiments, a pharmaceutical composition comprising one or more compounds of the present invention is administered in the form of a dosage unit (e.g., tablet, capsule, bolus, etc.). In certain embodiments, such dosage units comprise a selective TPO modulator in a dose from about 1 ug/kg of body weight to about 50 mg/kg of body weight. In certain embodiments, such dosage units comprise a selective TPO modulator in a dose from about 2 µg/kg of body weight to about 25 mg/kg of body weight. In certain embodiments, such dosage units comprise a selective TPO modulator in a dose from about 10 µg/kg of body weight to about 5 mg/kg of body weight. In certain embodiments, pharmaceutical compositions are administered as needed, once per day, twice per day, three times per day, or four or more times per day. It is recognized by those skilled in the art that the particular dose, frequency, and duration of administration depends on a number of factors, including, without limitation, the biological activity desired, the condition of the patient, and tolerance for the pharmaceutical composition.
In certain embodiments, the formulation, route of administration and dosage for a pharmaceutical composition of the present invention can be chosen in view of a particular patient's condition. (See e.g., Fingl et al. 1975, in "The Pharmacological Basis of Therapeutics",

Ch. 1 p. 1). In certain embodiments, a pharmaceutical composition is administered as a single dose. In certain embodiments, a pharmaceutical composition is administered as a series of two or more doses administered over one or more days.
In certain embodiments, a pharmaceutical composition of the present invention is administered to a patient between about 0.1% and 500%, more preferably between about 25% and 75% of an established human dosage. Where no human dosage is established, a suitable human dosage may be inferred from EDSO or ID50 values, or other appropriate values derived from in vitro or in vivo studies.
In certain embodiments, a daily dosage regimen for a patient comprises an oxal dose of between 0.1 mg and 2000 mg of a compound of the present invention. In certain embodiments, a daily dosage regimen is administered as a single daily dose. In certain embodiments, a daily dosage regimen is administered as two, three, four, or more than four doses .
In certain embodiments, a pharmaceutical composition of the present invention is administered by continuous intravenous infusion. In certain of such embodiments, from 0.1 rng to 500 mg of a composition of the present invention is administered per day.
In certain embodiments, a pharmaceutical composition of the invention is administered for a period of continuous therapy. For example, a pharmaceutical composition of the present invention may be administered over a period of days, weeks, months, or years.
Dosage amount, interval between doses, and duration of treatment may be adjusted to achieve a desired effect. In certain embodiments, dosage amount and interval between doses are adjusted to maintain a desired concentration on compound in a patient. For example, in certain embodiments, dosage amount and interval between doses are adjusted to provide plasma concentration of a compound of the present invention at an amount sufficient to achieve a desiied effect. In certain of such embodiments the plasma concentration is maintained above the minimal effective concentration (MEC). In certain embodiments, pharmaceutical compositions of the present invention are administered with a dosage regimen designed to maintain a concentration above the MEC for 10-90% of the time, between 30-90% of the time, or between 50-90% of the time.
In certain embodiments in which a pharmaceutical composition is administered locally, the dosage regimen is adjusted to achieve a desired local concentration of a compound of the present invention.
In certain embodiments, a pharmaceutical composition may be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for 'example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack: or

dispenser may also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of Pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, may be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
In certain embodiments, a pharmaceutical composition is in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. Certain Combination Therapies
In certain embodiments, one or more pharmaceutical compositions of the present invention are co-administered with one or more other pharmaceutical agents. In certain embodiments, such one or more other pharmaceutical agents are designed to treat the same disease or condition as the one or more pharmaceutical compositions of the present invention. In certain embodiments, such one or more other pharmaceutical agents are designed to treat a different disease or condition as the one or more pharmaceutical compositions of the present invention. In certain embodiments, such one or more other pharmaceutical agents are designed to treat an undesired effect of one or more pharmaceutical compositions of the present invention. In certain embodiments, one or more pharmaceutical compositions of the present invention are co-administered with another pharmaceutical agent to treat an undesired effect of that other pharmaceutical agent. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are administered at the same time. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are administered at the different times. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are prepared together in a single formulation. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are prepared separately.
Examples of pharmaceutical agents that may be co-administered with a pharmaceutical composition of the present invention include, but are not limited to, anti-cancer treatments, including, but not limited to, chemotherapy and radiation treatment; corticosteroids, including but not limited to prednisone; immunoglobulins, including, but not limited to intravenous immunoglobulin (IVIg); analgesics (e.g., acetaminophen); aati-inflammatory agents, including, but not limited to non-steroidal anti-inflammatory drugs (e.g., ibuprofen, COX-1 inhibitors, and COX-2, inhibitors); salicylates; antibiotics; antivirals; antifungal agents; antidiabetic agents (e.g.,

biguanides, glucosidase inhibitors, insulins, sulfonylureas, and thiazolidenediones); adrenergic modifiers; diuretics; hormones (e.g., anabolic steroids, androgen, estrogen, calcitonin, progestin, somatostan, and thyroid hormones); immunomodulators; muscle relaxants; antihistamines; osteoporosis agents (e.g., biphosphonates, calcitonin, and estrogens); prostaglandins, antineoplastic agents; psychotherapeutic agents; sedatives; poison oak or poison sumac products; antibodies; and vaccines. Certain Indications
In certain embodiments, the invention provides methods of treating a patient comprising administering one or more compounds of the present invention. In certain embodiments, such patient suffers from thrombocytopenia. In certain such embodiments, thrombocytopenia results from chemotherapy and/or radiation treatment. In certain embodiments, thrombocytopenia results bone marrow failure resulting from bone marrow transplantation and/or aplastic anemia. In certain embodiments thrombocytopenia is idiopathic. In certain embodiments, one or more compounds of the present invention are administered to a patient to in conjunction with harvesting peripheral blood progenitor cells and/or in conjunction with platelet apheresis. Such administration may be done before, during, and/or after such harvesting.
In certain embodiments, one or more compounds of the present invention are administered to a patient who suffers from a condition affecting the nervous system, including, but are not limited to, diseases affecting the nervous system and injuries to the nervous system. Such diseases, include, but not limited to, amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy. Injury to the nervous system include, but are not limited to spinal cord injury or peripheral nerve damage, including, but not limited to, injury resulting from trauma or from stroke. In certain embodiments, one or more compounds of the present invention are used to promote growth and/or development of glial cells. Such glial cells may repair nerve cells. In certain embodiments, compounds of the present invention are used to treat psychological disorders, including, but not limited to, cognitive disorders. In certain embodiments, one or more compounds of the invention are administered to enhance athletic performance.
Examples
The following examples, including experiments and results achieved, are provided for illustrative purposes only and are not to be construed as limiting the present invention.

Example 1: 3'-N-fl-(3.4-Dimethvl-phenvl)-2-oxo-1.2-dihvdro-indol-3-ylidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 101)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-d6~) 5 13.07 (s, IH), 13.03 (s, IH), 9.26 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.3 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.3 Hz, IH), 7.73 (dd, 7=7.9, 1.6 Hz, IH), 7.72 (m, IH), 7.60 (t, 7=7.7 Hz, IH), 7.35 (d, 7=8.1 Hz, IH), 7.30 (d, 7=2.1 Hz, IH), 7.28 (td, 7=7.7,1.3 Hz, IH), 7.23 (dd, 7=8.1, 2.1 Hz, IH), 7.18 (td, 7=7.7, 0.9 Hz, IH), 7.11 (t, 7=7.9 Hz, IH), 7.00 (dd, 7=7.9, 1.6 Hz, IH), 6.85 (m, IH), 2.31 (s, 3H), 2.30 (s, 3H).
Example 2: 2'-Hydroxv-3'-(N'-[2-oxo-l-(4-propvl-phenyl)-1.2-dihydro-indol-3-vlidene1-hvdrazino)-biphenvl-3-carboxvlic acid (Compound 1021
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 13.07 (s, IH), 13.03 (s, IH), 9.27 (s, IH), 8.11 (t, 7=1.6 Hz, IH), 7.94 (dt, 7=7.7, 1.6 Hz, IH), 7.79 (dt, 7=7.7, 1.6 Hz, IH), 7.73 (d, 7=7.9 Hz, IH), 7.73 (d, 7 =7.9 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.44 (d, J =8.5 Hz, 2H), 7.41 (d, J =8.5 Hz, 2H), 7.29 (td, J =7.7, 1.3 Hz, IH), 7.19 (td,.7=7.7, 1.0 Hz, IH), 7.11 (t,7=7.9Hz, IH), 7.00(dd,/ =7.7, 1.3 Hz, IH), 6.87 (dd,.7=7.7, 1.0 Hz, IH), 2.66 (t, J =7.3 Hz, 2H), 1.66 (sext, 7=7.3 Hz, 2H), 0.95 (t, 7 =7.3 Hz, 3H).
Example 3: 2'-Hvdroxv-3'-(N'-[2-oxo-l-('4-ethvl-phenvl)-1.2-dihvdro-indol-3-ylidene> hvdrazino)-biohenvl-3-carboxvlic acid (Compound 103)

(Figure Removed)
This compound was prepared as described in Scheme n. H NMR (500 MHz, DMSO-rffi) 5. 13.06 (s, IH), 13.03 (s, IH), 9.27 (s, IH), 8.11 (t, .7=1.5 Hz, IH), 7.94 (dt, 7=7.8, 1.5 Hz, IH), 7.79 (dt, .7=7.8,1.5 Hz, IH), 7.73 (dd, .7=7.8 Hz, IH), 7.73 (dd, .7=7.8 Hz, IH), 7.60 (t, J =7.8 Hz, IH), 7.45 (d,7=8.6 Hz, 2H), 7.43 (d, .7=8.6 Hz, 2H), 7.29 (td, 7=7.9,1.0 Hz, IH), 7.19 (td, 7=7.9, 1.0 Hz, IH), 7.11 (t, 7=7.8 Hz, IH), 7.00 (dd, 7=7.9, l.O Hz, IH), 6.87 (dd, 7=7.9, 1.0 Hz, IH), 2.71 (q, 7=7.6 Hz, 2H), 1.25 (t, 7=7.6 Hz, 3H).
Example 4: 2'-Hvdroxv-3'-IN'-[2-oxo-l-f4-trifluorQmethoxv-phnvlVl .2-dihvdro-indol-3-vlidenel-hvdrazino1--bit)henvl-3-carboxvlic acid (Conmound 104)
(Figure Removed)

This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 5 13.03 (s, IH), 9.30 (s, IH), 8.11 (t, 7=1.8 Hz, Iff), 7.94 (ddd, 7=7.8, 1.8, 1.2 Hz, IH), 7.79 (ddd, 7=7.8,1.8, 1.2 Hz, IH), 7.75 (dd, 7=7.7,1.0 Hz, IH), 7.74 (dd, 7=7.8, 1.6 Hz, IH), 7.72 (d, 7=8.9 Hz, 2H), 7.60 (t, 7=7.8 Hz, IH), 7.31 (td, 7=7.7, 1.0 Hz, IH), 7.22 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8,1.6 Hz, IH), 6.94 (dd, 7=7.7,1.0 Hz, IH).
ExampleS: 3'-IN'-ri-(3-Fluoro-4-methoxv-phenvD-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino-2'-hvdroxv-bit)henvl-3-carboxvlic acid (Compound IPS')

(Figure Removed)
This compound was prepared as described in Scheme H 1H NMR (500 MHz, DMSO-40 513.03 (s, IH), 9.28 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7,1.6,1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.74-7.71 (m, 2H), 7.60 (t, 7=7.7 Hz, IH), 7.50 (dd, 7=12.3, 2.2 Hz, IH), 7.38 (t, 7=8.8 Hz, IH), 7.35 (dd, 7=8.8, 2.2 Hz, IH), 7.29 (td, 7=7.7, 1.0 Hz, IH), 7.19 (td,7=7.7,1.0Hz, IH), 7.11 (t,7=7.7 Hz, IH), 7.00 (dd,7=7.7,1.6Hz, IH), 6.87 (dd,7=7.7, 1.0 Hz, IH), 3.93 (s, 3H).
Example 6: 3'-(N'-[l-(3.4-Diraethvl-phenvl)-2-oxo-1.2-dihydro-indol-3-vlidene1-hvdrazmol-2'-hvdroxv-biphenvl-4-carboxvlic acid (Compound 106")
(Figure Removed)
This compound was prepared as described in Scheme II. H NMR (500 MHz, DMSO-df) $ 13.07 (s, IH), 12.96 (s, IH), 9.30 (s, IH), 8.02 (d, .7=8.4 Hz, 2H), 7.74 (dd, .7=7.8, 1.6 Hz, IH), 7.72 (dd, 7=7.7, 1.0 Hz, IH), 7.68 (d, 7=8.4 Hz, 2H), 7.35 (d, 7 =8.0 Hz, IH), 7.30 (m, IH), 7.27 (td, .7=7.7, 1.0 Hz, IH), 7.23 (dd, 7=8.0, 2.1 Hz, IH), 7.18 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8, 1.6 Hz, IH), 6.85 (dd, 7=7.7, 1.0 Hz, IH), 2.31 (s, 3H),2.30 (s, 3H).
Example 7: 2'-Hvdroxv-3'-{N'-[2-oxo-l-f4-propvl-phenvl)-1.2-dihvdro-indol-3-vlidene> hvdrazinol-biphenvl-4-carboxvlic acid (Compound 107)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 13.06 (s, IH), 12.96 (s, IH), 9.31 (s, IH), 8.02 (d, 7=8.3 Hz, 2H), 7.75-7.72 (m, 2H), 7.68 (d, 7=8.3 Hz, 2H), 7.44 (d, 7=8.6 Hz, 2H), 7.41 (d, 7=8.6 Hz, 2H), 7.29 (td, 7=7.7, 1.0 Hz, IH), 7.19 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8, 1.6 Hz, IH), 6.87 (dd, 7=7.7,1.0 Hz, IH), 2.66 (t, 7=7.4 Hz, 2H), 1.66 (sext, 7=7.4 Hz, 2H), 0.95 (t, 7=7.4 Hz, 3H).

Example 8: 2'-Hvdroxv-3'-N-[2-Qxo-l-(4-ethyl-phenvl')-1.2-dihydro-indol-3-vlidene1-hvdrazino}-biphenvl-4-carboxvlic acid (Compound 108)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSCMj) 513.21 (s, IH), 8.47 (s, IH), 8.11 (d, .7=8.5 Hz, 2H), 7.79 (dd, 7=7.8, 1.6 Hz, IH), 7.76 (m, IH), 7.68 (d, 7=8.5 Hz, 2H), 7.47 (d, 7=8.5 Hz, 2H), 7.45 (d, .7=8.5 Hz, 2H), 7.29 (td, 7=7.7, 1.1 Hz, IH), 7.19 (td, 7=7.7, 1.1 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.02 (dd, 7=7.8, 1.6 Hz, IH), 6.92 (dd, 7=7.7,1.1 Hz, IH), 2.75 (q, 7=7.6 Hz, 2H), 1.29 (t, 7=7.6 Hz, 3H).
Example 9: 3'-{N'-[l-(4-tert-Butyl-phenyl)-2-oxo-l .2-dihydro-indol-3-ylidene]-hydrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 109)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, acetone-d) § 13.22 (s, IH), 8.20 (s, IH), 8.02 (d, 7=7.8 Hz, IH), 7.80-7.74 (m, 3H), 7.64 (d, 7=8.0 Hz, 2H), 7.58 (m, IH), 7.48 (d, 7=8.0 Hz, 2H), 7.29 (t, 7=7.7 Hz, IH), 7.19 (t, 7=7.7 Hz, IH), 7.11 (t, 7=7.8 Hz, IH), 7.00 (m, IH), 6.92 (d, 7=7.7 Hz, IH), 1.38 (s, 9H).

Example 10: 2'-Hvdroxv-3'-IN'-r2-oxo-l-(4-trifluoromethvl-phenvl)-1.2-dihvdro-indol-3-vlidenel-h.vdrazinol-biphenvl-3-carboxvlic acid C Compound 1101



(Figure Removed)
This compound was prepared as described in Scheme II. !H NMR (500 MHz, £ 13.04 (s, IH), 9.32 (s, IH), 8.12 (t, .7=1.5 Hz, IH), 7.98 (d, .7=8.5 Hz, 2H), 7.94 (dt, J =7.7, 1.5 Hz, IH), 7.83 (d, .7=8.5 Hz, 2H), 7.79 (dt, J =7.7, 1.5 Hz, IH), 7.77 (d, .7=7.8 Hz, IH), 7.74 (dd, J =7.6, 1.2 Hz, IH), 7.59 (t, .7=7.7 Hz, IH), 7.32 (td, .7=7.6, 1.2 Hz, IH), 7.24 (td, 7=7.6, 1.2 Hz, IH), 7.12 (t, .7=7.8 Hz, IH), 7.04 (d, 7=7.8 Hz, IH), 7.02 (dd, 7=7.6,1.2 Hz, IH).
Example 11: 3'-[N'-(l -Benzvl-5-chloro-2-ox(-l .2-dihvdro-indol-3-vlideneVhydrazino]-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 111)
(Figure Removed)
This compound was prepared as described in Scheme III. 'H NMR (500 MHz, DMSO-cQ $ 13.10 (s, IH), 13.03 (s, IH), 9.36 (s, IH), 8.13 (t, 7=1.7 Hz, IH), 7.95 (ddd, 7=7.7, 1.7,1.3 Hz, IH), 7.80 (ddd, 7=7.7,1.7,1.3 Hz, IH), 7.76 (dd, 7=7.7,1.6 Hz, IH), 7.68 (d, 7=2.1 Hz,

IH), 7.60 (t, .7=7.7 Hz, IH), 7.37-7.32 (m, 4H), 7.30 (dd, .7=8.5, 2.1 Hz, IH), 7.27 (m, IH), 7.11 (t, 7=7.7 Hz, IH), 7.09 (d, .7=8.5 Hz, IH), 7.03 (dd, .7=7.7, 1.6 Hz, IH), 5.05 (s, 2H).
Example 12: 3'-[N'-(l-Benzvl-5-methvl-2-oxo-1.2-dihvdro-indol-3-vlidene')-hvdrazinoV2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 112)

(Figure Removed)
This compound was prepared as described in Scheme HI. 1H NMR (500 MHz, 13.04 (s, IH), 13.03 (s, IH), 9.25 (s, IH), 8.13 (t, 7=1.5 Hz, IH), 7.94 (dt, .7=7.8, 1.5 Hz, IH), 7.80 (m, IH), 7.69 (dd, .7=7.8,1.6 Hz, IH), 7.60 (t, .7=7.8 Hz, IH), 7.48 (d, .7=1.8 Hz, IH), 7.37-7.31 (m, 4H), 7.27 (m, IH), 7.10 (t, .7=7.8 Hz, IH), 7.07 (dd, .7=8.1, 1.8 Hz, IH), 6.99 (dd, .7=7.8,1.6 Hz, IH), 6.95 (d, 7=8.1 Hz, IH), 5.01 (s, 2H), 2.33 (s, 3H).
Example 13: 3'-[N'-fl-Benzvl-2-oxo-1.2-dihvdro-indol-3-yIidenehvdrazino]-2'-hydroxy-biphenvl-3-carboxvlic acid ("Compound 113)
(Figure Removed)
This compound was prepared as described in Scheme III. 'H NMR (500 MHz, DMSO-40 £13.07 (s, IH), 13.04 (s, IH), 9.28 (s, IH), 8.13 (t, >1.5 Hz, IH), 7.94 (dm, .7=7.7 Hz;,
IH), 7.80 (dm, 7=7.7 Hz, IH), 7.70 (dd,7=7.8, 1.3 Hz, IH), 7.65 (d, 7=7.8 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.39-7.32 (m, 4H), 7.29r7.24 (m, 2H), 7.14-7.09 (m, 2H), 7.07 (d, .7=7.8 Hz, IH), 7.00 (dd, 7=7.8, 1.3 Hz, IH), 5.05 (s, 2H).
Example 14: 2l-Hvdroxv-3l-|N'-[2-oxo-l-(-4-trifluoromethvl-phenvD-1.2-dihvdro-indol-3-vlidenel-hvdrazinol-biphenvl-4-carboxvlic acid (Compound 1141
(Figure Removed)
This compound was prepared as described in Scheme U. 'H NMR (500 MHz, DMSO-4s) 8 13.03 (s, IH), 12.96 (s, IH), 9.36 (s, IH), 8.02 (d, 7=8.3 Hz, 2H), 7.98 (d, 7=8.3 Hz, 2H), 7.83 (d, 7=8.3 Hz, 2H), 7.77 (dd, 7=7.7, 1.2 Hz, IH), 7.75 (dd, 7=7.8, 1.6 Hz, IH), 7.68 (d, 7=8.3 Hz, 2H), 7.32 (td, 7=7.7, 1.2 Hz, IH), 7.24 (td, 7=7.7, 0.7 Hz, IH), 7.13 (t, 7=7.8 Hz, IH), 7.03 (dd, 7=7.8,1.6 Hz, IH) 7.04 (dd, 7=7.7, 0.7 Hz, IH).
Example 15: 3'-fNl-[l-(3.4-Dichloro-pheaylV2-oxo-l,2-dihvdro-indol-3-ylidene]-hvdrazino>-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 115)
(Figure Removed)


This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 13.04 (s, IH), 13.01 (s, IH), 9.32 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.95 (dt, 7=7.7, 1.4 Hz, IH), 7.93 (d, .7=2.4 Hz, IH), 7.88 (d, 7=8.5 Hz, IH), 7.79 (m, IH), 7.75 (ddd, .7=7.6, 1.0, 0.5 Hz, IH), 7.73 (dd, .7=7.7,1.6 Hz, IH), 7.61 (dd, 7=8.5,2.4 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.31 (td, 7=7.6, 1.0 Hz, IH), 7.22 (td, 7=7.6, 0.8 Hz, IH), 7.12 (t, 7=7.7 Hz, IH), 6.98 (ddd, 7=7.6, 0.8, 0.5 Hz, IH), 7.01 (dd, 7=7.7,1.6 Hz, IH). -
Example 16: 2'-Hydroxv-3'- IN'-[ 1 -(4-methyl-3-trifluoromethvl-phenvlV2oxo-l .2-dihvdro-indol-3-vlidene1-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 116)

(Figure Removed)
This compound was prepared as described in Scheme n. !H NMR (500 MHz, £ 13.04 (s, IH), 13.02 (s, IH), 9.30 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.8, 1.6,1.2 Hz, IH), 7.88 (d, 7=2.0 Hz, IH), 7.79 (ddd, 7=7.8,1.6,1.2 Hz, IH), 7.77 (dd, 7=8.3, 2.0 Hz, IH), 7.76-7.72 (m, 2H), 7.68 (d, 7=8.3 Hz, IH), 7.60 (t, 7=7.8 Hz, IH), 7.30 (td, 7=7.7,1.2 Hz, IH), 7.21 (td, 7=7.7, 0.9 Hz, IH), 7.12 (t, 7=7.7 Hz, IH), 7.01 (dd, 7=7.7, 1.6 Hz, IH), 6.92 (dm, 7=7.7 Hz, IH), 2.54 (q, 7=1.4 Hz, 3H).

Example 17: S'-IN'-ri-O-Fluoro-trifluoromethyl-phenyD-oxo-l-dihvdro-indol-S-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 117)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-4,) 5 13.04 (s, IH), 13.01 (s, IH), 9.35 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 8.03 (t, 7=8.4 Hz, IH), 7.94 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.86 (dd, .7=11.8, 1.5 Hz, IH), 7.80 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.77 (dd, .7=7.7, 1.0 Hz, IH), 7.74 (dd, .7=7.7, 1.6 Hz, IH), 7.68 (dd, .7=8.4, 1.5 Hz, IH), 7.60 (t, .7=7.7 Hz, IH), 7.34 (td, 7=7.7, 1.0 Hz, IH), 7.25 (td, 7=7.7, 1.0 Hz, IH), 7.14 (dd, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.7 Hz, IH), 7.02 (dd, 7=7.7,1.6 Hz, IH).
Example 18: 3'-(N'-[l-(3.5-Bis-trifluoromethyl-phenyl)-2-oxo-l .2-dihydro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 118)


(Figure Removed)
This compound was prepared as described in Scheme II. !H NMR (500 MHz, DMSO-rf,) 8 13.04 (s, IH), 12.99 (s, IH), 9.34 (s, IH), 8.38-8.37 (m, 2H), 8.27 (m, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.78 (ddd,
J=7.7, 1.3, 0.6 Hz, IH), 7.75 (dd, .7=7.8, 1.7 Hz, IH), 7.60 (t, 7=7.7 Hz,-lH), 7.34 (td, ,7=7.7, 1.3 Hz, IH), 7.25 (td, 7=7.7, 1.0 Hz, IH). 7.13 (t, 7=7.8 Hz, IH), 7.02 (dd, 7=7.8, L .7 Hz, IH), 7.02 (ddd, 7=7.7, 1.0, 0.6 Hz, IH).
Example 19: 3'-IN'-[3-(3.4-Dime1hyl-phenvl)-4-oxo-2-thioxo-1hiazolidin-5-vli(lene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 1191

(Figure Removed)
This compound was prepared as described in Scheme IV. 1H TMMR (500 MHz, DMSO-rf,) $ 12.83 (s, IH), 10.76 (s, IH), 9.35 (s, IH), 8.15 (t,7=1.5 Hz, IH), 7.91 (m, IH), 7.79 (dt, 7=7.7,1.5 Hz, IH), 7.56 (t, 7=7.7 Hz, IH), 7.34 (m, IH), 7.29 (d, 7=7.9 Hz, 1 H), 7.14-6.96 (m, 4H), 2.28 (s,3H), 2.26 (s,3H).
Example 20: 2'-Hvdroxv-3'-IN'-[l-(4-isopropvl-phenvl')-2-oxo-1.2-dihvdro-ind.ol-3-vlidene]-hvdrazino}-bit)henvl-3-carboxvlic acid (Compound 120)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DM.SO-ds) 5. 13.06 (s, IH), 9.27 (s, IH), 8.11 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7,1.7, 1.2 Hz, IH), 7.73 (dd, 7=7.7, 1.3 Hz, IH), 7.73 (dd, 7=7.7, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.47 (d, 7=8.8 Hz, 2H), 7.45 (d, 7=8.8 Hz, 2H), 7.29 (td, 7=7.7,1.3 Hz, IH), 7.19 (td, 7=7.7, 0.8 Hz, IH), 7.11 (t, 7=7.7 Hz, IH), 7.00 (dd, .7=7.7, 1.6 Hz, IH), 6.88 (dd, 7=7.7, 0.8 Hz, IH), 3.00 (sept, 7=6.9 Hz, IH), 1.27 (d,7=6.9 Hz, 6H).
Example 21: 3'-(N'-ri-(2-Fluoro-4-trifluoromethvI-phenvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 121)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-40 § 12.95 (s, IH), 9.34 (s, IH), 8.11 (t, 7=1.7 Hz, IH), 8.09 (m, IH), 7.96 (t, 7=8.0 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.86 (m, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.77 (m, IH), 7.75 (dd, 7=8.0, 1.5 Hz, IH), 7.60 (t, 7=7.7 Hz, 1H)9 7.32 (td, 7=7.6, 1.4 Hz, IH), 7.24 (td, 7=7.6,0.9 Hz, IH), 7.13 (t, 7=7.7 Hz, IH), 7.03 (dd, 7=7.7, 1.6 Hz, IH), 6.86 (dm, 7=7.6 Hz, IH).
Example 22: 3'-IN'-1-(2-Fluoro-4-methvl-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 122)
(Figure Removed)
This compound was prepared as described in Scheme E. 'H NMR (500 MHz, 12.99 (s, IH), 9.29 (s, IH), 8.11 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7,1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.75-7.72 (m, 2H), 7.59 (t, 7=7.7 Hz, IH), 7.52 (t, 7=8.0 Hz, IH), 7.37 (dd, 7=11.3, 1.4 Hz, IH), 7.29 (td, 7=7.7, 1.2 Hz, IH), 7.25 (dm, 7=8.0 Hz, IH), 7.21 (td, 7=7.7, 1.0 Hz, IH) 7.12 (t, 7=7.7 Hz, IH), 7.01 (dd, 7=7.7, 1.6 Hz, IH), 6.71 (dm, 7=7.7 Hz, IH), 2.43 (s, 3H).
Example 23: 3'-(N'-[l-(4-Chloro-3-trifluoromethvl-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 123)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dtf) 512.99 (s, IH), 9.32 (s, IH), 8.12 (m, 2H), 7.98 (d, 7=8.7 Hz, IH), 7.94 (dd, 7=8.7, 2.2 Hz, IH), 7.94 (m, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.76 (dd, 7=7.6, 1.0 Hz, IH), 7.74 (dd,
7=7.9, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.32 (td, 7=7.6, 1.4 Hz, IH), 7.23 (td, 7=7.6, 1.0 Hz, IH), 7.12 (t, 7=7.9 Hz, IH), 7.03-7.00 (m, 2H).
Example 24: 3'-(N'-[l-(4-Butyl-phenvl)-2-oxo-1.2-dihydro-mdol-3-ylidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 124)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-rf,) §13.22 (s, IH), 8.19 (t, 7=1.6 Hz, IH), 8.03 (dt, 7=7.8, 1.6 Hz, IH), 7.79 (dt, 7=7.8,1.6 Hz, IH), 7.78 (dd, 7=7.8,1.6 Hz, IH), 7.76 (dd, 7=7.7, 1.0 Hz, IH), 7.60 (t, 7=7.8 Hz, IH), 7.46 (d, 7=8.4 Hz, 2H), 7.44 (d, 7=8.4 Hz, 2H), 7.29 (td, 7=7.7, 1.0 Hz, IH), 7.19 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8,1.6 Hz, IH), 6.92 (d, 7=7.7, 1.0 Hz, IH), 2.72 (t, 7=7.5 Hz, 2H), 1.67 (m, 2H), 1.40 (m, 2H), 0.95 (t, 7=7.5 Hz, 3H).

Example 25: 3'-fN'-[l-(3-Fluoro-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 125)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-d,) £13.03 (s, IH), 9.31 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.74 (ddd, 7=7.6,1.2, 0.6 Hz, IH), 7.73 (dd, 7=7.7, 1.6 Hz, IH), 7.65 (ddd, 7=8.5, 8.0, 6.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.49 (ddd, 7=9.9, 2.6, 2.0 Hz, IH) 7.42 (ddd, 7=8.0, 2.0, 0.8 Hz, IH), 7.36 (tdd, 7=8.5, 2.6, 0.8 Hz, IH), 7.31 (td, 7=7.6, 1.2 Hz, IH), 7.21 (td, 7=7.6, 0.8 Hz, IH), 7.11 (t, 7=7.7 Hz, IH), 7.01 (dd, 7=7.7, 1.6 Hz, IH), 6.96 (ddd, 7=7.6, 0.8, 0.6 Hz, IH).
Example 26: 2'-Hydroxv-3'-[N'-f2-oxo-l-m-tolvl-1.2-dihvdro-indol-3-vlidene)-hvdrazino]-biphenvl-3-carboxylic acid (Compound 126)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dfi) §13.22 (s, IH), 8.20 (t, 7=1.6 Hz, IH), 8.03 (dt, 7=7.8, 1.6 Hz, IH), 7.80-7.77 (m, 2H), 7.76 (dd, 7=7.7,1.0 Hz, IH), 7.60 (t, 7=7.8 Hz, IH), 7.48 (t, 7=7.8 Hz, IH), 7.38 (t, 7=1.6 Hz, IH),

7.35 (m, IH), 7.30 (m, IH), 7.29 (td, .7=7.7, 1.0 Hz, IH), 7.19 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, .7=7.8, 1.7 Hz, IH), 6.93 (dd, .7=7.7,1.0 Hz, IH), 2.44 (s, 3H).
Example 27: 3'-{N'-ri-(4-Fluoro-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidene]-h.vdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 127)

(Figure Removed)
This compound was prepared as described in Scheme n. 1H NMR (500 MHz, DMSO-de) 13.04 (s, IH), 9.28 (s, IH), 8.11 (t, J=l.6 Hz, IH), 7.94 (dt, 7=7.9, 1.6 Hz, IH), 7.78 (dt, .7=7.9, 1.6 Hz, IH), 7.74 (dd, 7=7.8, 1.0 Hz, IH), 7.73 (dd, .7=7.9, 1.6 Hz, IH), 7.63-7.57 (m, 3H), 7.44 (t, 7=8.6 Hz, 2H), 7.29 (td, 7=7.8,1.0 Hz, IH), 7.20 (td, 7=7.8, 1.0 Hz, IH), 7.11 (t, 7=7.9 Hz, IH), 7.00 (dd, 7=7.9,1.6 Hz, IH), 6.86 (d, 7=7.8 Hz, IH).
Example 28: 3'-[N'-(l-Benzvl-5-methoxy-2-oxo-1.2-dihvdro-indol-3-vlidene)-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid ("Compound 128)
(Figure Removed)
This compound was prepared as described in Scheme HI. 'H NMR (500 MHz, DMSO-dff) 8 13.10 (s, IH), 9.27 (s, IH), 8.13 (s, IH), 7.95 (d, 7= 7.5 Hz, IH), 7.80 (d, 7= 8.0 Hz, IH), 7.74 (d, 7= 6.5 Hz, IH), 7.60 (t, 7= 7.5 Hz, IH), 7.36-7.32 (m, 4H), 7.28-7.25 (m, IH), 7.24
(d, J= 2.5 Hz, IH), 7.11 (t, J = 7.5 Hz, IH), 7.00 (d, J= 8.0 Hz, IH), 6.97 (d, J = 8.5 Hz, IH), 6.84 (dd, /= 2.5, 9.0 Hz, IH), 5.01 (s, 2H), 3.79 (s, 3H).
Example 29: 2'-Hvdroxv-3'-(N'-r2-oxo-l-(3-trifluoromethvl-phenvn-1.2-dihvdro-indol-3-vlidenel-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 129)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-4,) 5 13.03 (s, IH), 9.32 (s, IH), 8.12 (s, IH), 7.99 (s, IH), 7.95-7.91 (m, 4 H), 7.81-7.73 (m, 3H), 7.60 (t, J = 7.5 Hz, IH), 7.32 (t, J= 7.5 Hz, IH), 7.23 (t, J= 7.5 Hz, IH), 7.12 (t, J= 7.5 Hz, IH), 7.02 (dd, J= 1.5,7.5 Hz, IH), 6.95 (d, J= 7.5 Hz, IH).
Example 30: 3'-{N'-r5-Chloro-l-f4-isopropvl-phenvl')-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazino)-2'-hvdroxv-bit)henvl-3-carboxvlic acid (Compound 1301



(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-rftf) §13.09 (s, 2H), 9.35 (s, IH), 8.11 (d, .7=1.5 Hz, IH), 7.94 (d, .7=7.8 Hz, IH), 7.79 (d, .7=8.3 Hz, 2H), 7.76 (d, .7=2.0 Hz, IH), 7.60 (t, IH), 7.46 (q, .7=6.0 Hz, 4H), 7.30 (dd, .7=8.3, 2.4 Hz,

IH), 7.12 (t, 7=7.8 Hz, IH), 7.03 (dd, 7=7.8, 1.5 Hz, IH), 6.88 (d, 7=8.8 Hz, IH), 3.00 (sept, 7=7.0 Hz, IH), 1.27 (d, .7=6.8 Hz, 8H).
Example 31: 3'- {N'-[6-Chloro-1 -(4-isopropvl-phenvl)-2-oxo-1.2-dihvdro-indol-3 -vlidene]-hvdrazino)-2'-hvdroxv-biDhenvl-3-carboxvlic acid (Compound 131")
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 813.05 (s, IH), 9.30 (s, IH), 8.11 (t, .7=1.5 Hz, IH), 7.94 (qn, 7=2.3 Hz, IH), 7.79 (dt, .7=7.8, 1.5 Hz, IH), 7.73 (dd, 7=7.8, 1.5 Hz, 2H), 7.59 (t, 7=7.8 Hz, IH), 7.48 (m, 4H), 7.24 (dd, 7=8.1, 1.7 Hz, IH), 7.11 (t, IH), 7.02 (dd, 7=7.6, 1.7 Hz, IH), 6.82 (d, 7=1.5 Hz, IH), 3.00 (sept, 7=6.8 Hz, IH), 1.27 (d, 7=6.8 Hz, 6H).
Example 32: 3l-(N'-r5-Fluoro-l-(4-isopropvl-phenyl)-2-oxo-1.2-dihydro-indol-3-vlidene> hvdrazinol-2'-hvdroxv-bii3henvl-3-carboxvlic acid (Comoound 132)

(Figure Removed)
This compound was prepared as described in Scheme DL 'H NMR (500 MHz, DMSO-de) 813.12 (s, IH), 13.04 (s, lH),9.34(s, 1H),8.11 (t, IH), 7.94 (t, IH), 7.78 (dt,/=9.1.5.2 Hz, 2H), 7.58 (m, 2H), 7.46 (m, 4H), 7.09-7.09 (m, 2H), 7.03 (dd, 7=7.8, 2.0 Hz, IH), 6.87 (dd, J=8.8, 3.9 Hz, IH), 3.00 (sept, 7=7.0 Hz, IH), 1.27 (d, 7=6.8 Hz, 6H).
Example 33: 3'- (N'-f5 -Methoxv-1 -C4-isopropvl-phenvl)-:2-oxo-1.2-dihydro-indol-3 -vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compovmd 133)
(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-40 513.09 (s, IH), 13.03 (s, IH), 9.26 (s, IH), 8.11 (t, .7=1.5 Hz, IH), 7.94 (d, .7=7.8 Hz, IH), 7.78 (dt, 7=9.9, 5.5 Hz, 2H), 7.60 (t, 7=7.8 Hz, IH), 7.45 (q, 7=5.4 Hz, 4H), 7.32 (d, 7=2.4 Hz, IH), 7.11 (t, IH), 7.00 (dd, 7=7.6, 1.7 Hz, IH), 6.86 (dd, 7=8.5, 2.7 Hz, IH), 6.82 (d, 7=8.8 Hz, IH), 3.83 (s,3H), 3.00 (sept, 7=6.8 Hz, IH), 1.27 (d, 7=6.8 Hz, 6H).
Example 34: 3'-(N'-ri-(3.4-Diniethvl-phenYl)-5-fluoro-Z-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdroxv-bit)henvl-3-carboxvlic acid (Compound 134)
(Figure Removed)
This compound was prepared as described in Scheme II. 1H NMR (500 MHz, DMSO-4,) 513.13 (s, IH), 13.03 (s, IH), 9.33 (s, IH), 8.12 (t, IH), 7.94 (d, .7=7.8 Hz, IH), 7.79 (dt, J=4.8, 3.8 Hz, 2H), 7.60 (t, .7=7.8 Hz, IH), 7.56 (dd, .7=8.1, 2.7 Hz, IH), 7.35 (d, 7=8.3 Hz, IH), 7.30 (d, .7=2.0 Hz, IH), 7.23 (dd, 7=8.1, 2.2 Hz, IH), 7.14-7.08 (m, 2H), 7.03 (dd, 7=7.8, 1.5 Hz, IH), 6.85 (q, .7=4.2 Hz, IH), 2.31 (s, 3H), 2.30 (s, 3H).
Example 35: 3'-IN'-[l-(4-Fluoro-3-trifluoromethvl-phenvl)-5-fluoro-2-oxo-1.2-dihydro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biDhenvl-3-carboxvlic acid (Compound 135)



(Figure Removed)
This compound was prepared as described in Scheme II. H NMR (500 MHz, DMSO-4) 813.03 (s, IH), 13.00 (s, IH), 9.31 (s, IH), 8.12 (t, .7=1.6 Hz, IH), 8.06 (dd, 7=6.6, 2.7 Hz, IH), 7.99 (dd, 7=8.8, 4.4, 2.7 Hz, IH), 7.94 (ddd, 7=7.8, 1.6, 1.3 Hz, IH), 7.80-7.72 (m, 4H), 7.60 (t, 7=7.8 Hz, IH), 7.31 (td, 7=7.7,1.3 Hz, IH), 7.22 (td, 7=7.7, 1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8,1.6 Hz, IH), 6.94 (ddd, 7=7.7, 1.0,0.6 Hz, IH).
Example 36: 3'- (N'-[ 1 -(3.5 -Dichloro-phenvl)-5-fluoro-2-oxo-1.2-dihydro-indol-3 -vlidenel -hvdrazino-2'-hvdroxv-biphenyl-3-carboxvlic acid (Compound 136)
(Figure Removed)
This compound was prepared as described in Scheme H 1H NMR (500 MHz, DMSO-4) 5 13.02 (s, IH), 12.99 (s, IH), 9.33 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7,

1.6,1.1 Hz, IH), 7.80 (ddd, 7=7.7, 1.6,1.1 Hz, IH), 7.78 (t, .7=1.9 Hz, IH), 7.76-7.72 (m, 4H), 7.60 (t, .7=7.7 Hz, IH), 7.32 (td, .7=7.6, 1.2 Hz, IH), 7.23 (td, 7=7.6, 0.7 Hz, IH), 7.12 (t, .7=7.8 Hz, IH), 7.01 (dd, .7=7.8, 1.7 Hz, IH), 7.00 (d, ,7=7.6 Hz, IH).
Example 37: 3'- (N'-ri-Propvl-phenylVe-cMor-oxo-l-dihydro-indol-S-vlidenel-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 137)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-40 513.05 (s, IH), 13.02 (s, IH), 9.32 (s, IH), 8.11 (t, .7=1.7 Hz, IH), 7.94 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.73 (dd, .7=8.0, 1.8 Hz, IH), 7.73 (d, .7=8.0 Hz, IH), 7.59 (t, 7=7.7 Hz, IH), 7.45 (d, .7=8.6 Hz, 2H), 7.42 (d, .7=8.6 Hz, 2H), 7.23 (dd, .7=8.0,1.9 Hz, IH), 7.11 (dd, 7=7.7, 8.0 Hz, IH), 7.02 (dd, ,7=7.7, 1.8 Hz, IH), 6.81 (d, .7=1.9 Hz, IH), 2.66 (t, 7=7.4 Hz, 2H), 1.66 (sext, .7=7.4 Hz, 2H), 0.95 (t, 7=7.4 Hz, 3H).
Example 38: (+)-2'-Hvdroxv-3 '-W- l2-oxo-l-[4-(2.2.2-trifluoro-1 -hydroxv-ethylVphenyl]-! .2-dihvdro-indol-3-vlidene}-hvdrazino)-biphenvl-3-carboxvlic acid (Compound 138)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-46) 5 13.05 (s, IH), 13.03 (s, IH), 9.29 (s, IH), 8.12 (s, IH), 7.94 (d, 7=7.8 Hz, IH), 7.79 (d,

J=7.8 Hz, IH), 7.76-7.70 (m, 4H), 7.62-7.59 (m, 3H), 7.30 (t, 7=7.6 Hz, IH), 7.21 (t, .7=7.6 Hz, IH), 7.12 (t, 7=7.9 Hz, IH), 7.02-6.99 (m, 2H), 6.93 (d, .7=7.8 Hz, IH), 5.32 (m, IH), 3.17 (d, .7=5.3 Hz, IH).
Example 39: (±)-2'-Hvdroxv-3l-(N-(2-oxo-l-r4-('2.2.2-trifluoro-l-methoxv-ethvn-phen-vn-1.2-dihvdro-indol-3-vlidenel-hvdrazino)-biphenvl-3-carboxvlic acid (Compound 1391

(Figure Removed)
This compound was prepared as described in Scheme II. :H NMR (500 MHz, DMSO-4f) 513.06 (s, IH), 13.03 (s, IH), 9.30 (s, IH), 8.12 (s, IH), 7.94 (d, 7=7.0 Hz, IK}, 7.79 (d, 7=7,0 Hz, IH), 7.75 (m, 2H), 7.68 (m, 4H), 7.60 (t, 7=7.0 Hz, IH), 7.31 (t, 7=7.4 Hz, Iff), 7.22 (t, 7=7.4 Hz, IH), 7.12 (t, 7=7.6 Hz, IH), 7.01 (d, 7=7.6 Hz, IH), 6.97 (m, IH), 5.22 (q, 7=6.7 Hz, IH), 3.42 (s, 3H).
Example 40: 2'-Hvdroxv-3'-(N-(2-oxo-l-r4-('2.2.2-trifluoro-ethvl)phenvl1-1.2-dihvdro.-mdol-3-ylidene)-hydrazino)-biphenyl-3-carboxvlic acid (Compound 140)

(Figure Removed)
This compound was prepared as described in Scheme EL 'H NMR (500 MHz, DMSO-40 5 13.05 (s, IH), 13.02 (s, IH), 9.28 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.74 (m, 2H), 7.62-7.56 (m, 5H), 7.30 (td, 7=7.6, 1.2 Hz, IH), 7.21 (td, 7=7.6, 0.8 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.01 (dd, 7=7.8, 1.6 Hz, IH), 6.92 (d, 7=7.8, IH), 3.79 (q, 7=11.5 Hz, 2H).

Example 41: 3'4Ari-(3.44)imethvl-phenvlM.5-dimethvl-2-oxo-l .2-dihydro-indol-3-vlidene]-hvdra2ano}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 141)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, CD3OD) 88.17 (s, IH), 8.00 (d, 7=7.7 Hz, IH), 7.74 (d, 7=7.7 Hz, IH), 7.65 (d, 7=7.7 Hz, IH), 7.54 (t, 7=7.7 Hz, IH), 7.32 (d, 7=7.7 Hz, IH), 7.21 (s, IH), 7.15 (d, 7=7.7 Hz, IH), 7.08 (t, 7=7.7 Hz, IH), 7.02 (m, IH), 6.95 (d, 7=7.7 Hz, IH), 6.57 (m, IH), 2.72 (s, 3H), 2.35 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H).
Example 42: 3'-{N-[H3.4-Dimethvl-phenvl)-5-fluoro-4-methvl-2-oxo-l .2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 1421

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-40 513.29 (s, IH), 8.11 (s, IH), 7.91 (d, 7=7.3 Hz, IH), 7.74 (d, 7=7.3 Hz, IH), 7.61 (d, 7=7.8 Hz, IH), 7.54 (t, 7=7.3 Hz, IH), 7.35 (d, 7=8.0 Hz, IH), 7.28 (s, IH), 7.21 (dd, 7=8.0,1.7 Hz, IH), 7.10 (m, IH), 7.06 (t, 7=9.3 Hz, IH), 7.01 (d, 7=7.8 Hz, IH), 6.65 (dd, 7=8.6, 3.8 Hz, IH), 2.63 (br s, 3H), 2.31 (s, 3H), 2.30 (s, 3H).

Example 43: 3'- N-F1-C3.4-Dimethvl-phenvl)-5 -fluoro-6-methvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdro.xv-biphenvl-3-carboxvlic acid (Compound 143)

(Figure Removed)
This compound was prepared as described in Scheme II. *H NMR (300 MHz, DMSCMf) 5 9.28 (s, IH), 8.11 (t, .7=1.6 Hz, IH), 7.94 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.79 (ddd, J=7.6, 1.6, 1.2 Hz, IH), 7.74 (dd, .7=7.9, 1.6 Hz, IH), 7.59 (t, .7=7.7 Hz, IH), 7.49 (d, .7=9.0 Hz, IH), 7.35 (d, .7=8.0 Hz, IH), 7.28 (d, /=2.1 Hz, IH), 7.22 (dd, .7=8.0,2.1 Hz, IH), 7.11 (t, .7=7.9 Hz, IH), 7.01 (dd, .7=7.9, 1.6 Hz, IH), 6.74 (d, .7=5.8 Hz, IH), 2.31 (s, 3H), 2.30 (s, 3H), 2.24 (d, .7=1.8 Hz,3H).
Example 44: 5-(4-{N-[l-(3.4-Dimethyl-phenvn-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-3-hvdroxv-benzvlidene)-thiazolidine-2.4-dione (Compound 144)

(Figure Removed)
This compound was prepared as described in Scheme V. :H NMR (500 MHz, DMSO-d6 8 13.13 (s, 1H),12.57 (s, IH), 10.88 (s, IH), 7.92 (d, .7=7.9 Hz, IH), 7.82 (d, 7=8.4 Hz, IH), 7.70 (s, IH), 7.55 (d, .7=8.1 Hz, IH), 7.39 (d, 7=7.9 Hz, IH), 7.33 (br s, IH), 7.28-7.24 (m, 2H), 7.16 (br s, IH), 6.96 (s, IH), 2.33 (s, 3H), 2.31 (s, 3H).

Example 45: 5-(4-I{N-[l-(3.4-Dimethvl-phenvl)-2-oxo-l .2-dihvdro-indol-3-ylidene]-hvdrazino}-3-hvdroxv-ben2vlidene)-thiazolidine-2.4-dione (Compound 145)

(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-40 §13.00 (s, IH), 12.54 (s, IH), 10.74 (s, IH), 7.76 (d, 7=8.3 Hz, IH), 7.72 (d, 7=7.5 Hz, IH), 7.68 (s, IH), 7.36 (d, 7=8.3 Hz, IH), 7.32-7.29 (m, 2H), 7.25-7.22 (m, 2H), 7.19 (t, 7=7.5, IH), 7.15 (d, 7=1.8 Hz, IH), 6.86 (d, 7=7.5 Hz, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 46: 3'-{N-[l-(3.4-Dimethvl-phenvl)-4-fluoro-2-oxo-6-trifluoromethyl-1.2-dihvdro-mdol-3-vlidene1-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 146)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-rftf) §13.37 (s, IH), 13.05 (s, IH), 9.49 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.95 (ddd, 7=7.7,1.6, 1.2 Hz, IH), 7.80 (ddd, 7=7.7, 1.6, 1.3 Hz, IH), 7.67 (dd, 7=7.9, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.50 (d, 7=9.5 Hz, IH), 7.39 (d, 7=8.0 Hz, IH), 7.32 (d, 7=2.1 Hz, IH), 7.26 (dd, 7=8.0, 2.1 Hz, IH), 7.15 (t, 7=7.9 Hz, IH), 7.08 (dd, 7=7.9, 1.6 Hz, IH), 6.81 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).

Example 47: 3'-N-r4-Chloro-l-f3.4-dimethvl-phenvl)-2-oxo-6-trifluoroinethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazmol-2'-hvdroxv-biphenvl-3-carboxvlic acid fCompound 147)

(Figure Removed)
This compound was prepared as described in Scheme DC. 'H NMR (500 MHz, DMSO-d6) 513.45 (s, IH), 13.06 (s, IH), 9.51 (s, IH), 8.12 (t,.7=1.6 Hz, IH), 7.95 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.80 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.74 (dd, 7=7.8, 1.5 Hz, IH), 7.62 (m, IH), 7.60 (t, 7=7.7 Hz, IH), 7.39 (d, 7=8.2 Hz, IH), 7.32 (d,7=2.1 Hz, IH), 7.26 (dd, 7=8.2, 2.1 Hz, IH), 7.16 (t, 7=7.8 Hz, IH), 7.09 (dd, 7=7.8,1.5 Hz, IH), 6.89 (m, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 48: 5-(4-N-[l-(3.4-Dimethvl-phenyl)-4-fluoro-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidenel-hvdrazinol-3-hvdroxv-benzvlidene)-thiazolidine-2.4-dione (Compound 148)

(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-40 513.26 (s, IH), 12.57 (s, IH), 10.91 (s, IH), 7.69 (d, 7=8.3 Hz, IH), 7.66 (s, IH), 7.51 (d, 7=9.4 Hz, IH), 7.39 (d,7=8.3 Hz, IH), 7.32 (d, 7=1.9 Hz, IH), 7.27 (s, IH), 7.25 (d, 7= 1.9 Hz, IH), 7.17 (d, 7=1.9 Hz, IH), 6.80 (s, IH), 2.33 (s, 3H), 2.31 (s, 3H).

Example 49: 5 -(4- N-|4-Chloro-1 -(3,4-dimethvl-phenvI )-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-vlidene1-hvdrazino}-3-hvdroxv-benzvlidenei-thiazolidine-2.4-dione (Compound 149)

(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, 513.33 (s, IH), 12.58 (s, IH), 10.94 (s, IH), 7.76 (d, 7=8.3 Hz, IH), 7.70 (s, IH), 7.63 (s, IH), 7.39 (d, .7=8.0 Hz, IH), 7.32 (d, .7=1.9 Hz, IH), 7.27 (dt, 7=8.3, 1.9 Hz, IH), 7.26 (d, .7=8.0, IH), 7.17 (d, .7=1.9 Hz, IH), 6.88 (s, IH), 2.33 (s, 3H), 2.31 (s, 3H).
Example SO: 3-(4- N-[ 1 -(3.4-Dimernvl-phenvl)-2-oxo-6-trifluoromethvl-l.2-dihvdro-indol-3-vlidenel-hvdrazmol-3-hvdroxv-phenvlVacrvlic acid (Compound ISO)

(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-dtf) 813.12 (s, IH), 12.33 (s, IH), 10.68 (s, IH), 7.92 (d, /=7.8 Hz, IH), 7.73 (d, .7=8.3 Hz, IH), 7.53-7.52 (m, 2H), 7.39 (d, 7=8.4 Hz, IH), 7.33-7.31 (m, 2H), 7.26 (dd, 7=8.3, 2.1 Hz, IH), 7.15 (d, 7=1.8 Hz, IH), 6.95 (s, IH), 6.33 (d, 7=15.9 Hz, IH), 2.33 (s, 3H), 2.31 (s, 3H).

Example 51: l-(3.4-Dimethvl-phenvl1-3-ir2-hvdroxv-4-(4-oxo-2-thioxo-thiazolidin-5-vlidenemethvl)-phenvn-hvdrazon.o}-6-trifluoromethvl-1.3-dihvdro-indol-2-one (Compound 1511
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, tf) $13.81 (s, IH), 13.14 (s, IH), 10.90 (s, IH), 7.92 (d, .7=7.8 Hz, IH), 7.82 (d, .7=8.3 Hz, IH), 7.56-7.55 (m, 2H), 7.39 (d, .7=8.0 Hz, IH), 7.33 (d, .7=2.1 Hz, IH), 7.29-7.27 (m, 2H), 7.15 (d, .7=1.8 Hz, IH), 6.96 (m, IH), 2.33 (s, 3H), 2.31 (s, 3H).
Example 52: l-(3.4-Dimethyl-phenvl1-4-fluoro-3-([2-hvdroxv-4-(4-oxo-2-thioxo-thiazolidin-5-vlidenemethvll-Dhenvfl-hvdrazono\ -6-trifluoromethvl-1.3-dihvdro-indol-2-one (Compound 1521
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-rf,) ?13.81 (s, IH), 13.27 (s, IH), 10.94 (s, IH), 7.70 (d, .7=8.4 Hz, IH), 7.55 (s, IH), 7.52 (d, .7=9.9 Hz, IH), 7.39 (d, 7=8.0 Hz, IH), 7.32-7.30 (m, 2H), 7.26 (dd, .7=8.0, 1.6 Hz, IH), 7.16 (s, IH), 6.81 (s, IH), 2.33 (s, 3H), 2.31 (s, 3H).

Example 53: 5-(3- N-[ 1 -(3 .4-Dime1hvl-phenvl)-2-oxo-6-lrifluorome1:hvI-1.2-dihydro-indol-3 -vlidene1-hvdrazino}-2-hvdroxv-benzvlideneVthiazolidine-2.4-dione (Compound 153)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-dtf) S 13.16 (s, IH), 8.05 (s, IH), 7.91 (d, 7=7.7 Hz, IH), 7.81 (m, IH), 7.53 (d, .7=7.7, IH), 7.39 (d, .7=8.2 Hz, IH), 7.33 (d, .7=2.0 Hz, IH), 7.27 (dd, .7=8.2, 2.0 Hz, IH), 7.17-7.12 (m, 2H), 6.95 (s, IH), 2.33 (s, 3H), 2.31 (s, 3H).
Example 54: 3'-(N'-[5-Chloro-2-oxo-l-(4-propvl-phenvl')-1.2-dihvdro-indol-3-ylidene]-l-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 154)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-4,) 13.09 (s, IH), 13.02 (s, IH), 9.35 (s, IH), 8.12 (t, .7=1.6 Hz, IH), 7.94 (ddd, .7=7.8, 1.6, 1.2 Hz, IH), 7.81-7.78 (m, 2H), 7.76 (d, 7=2.2 Hz, IH), 7.60 (t, 7=7.8 Hz, IH), 7.43 (d, 7=8.8 Hz, 2H), 7.41 (d, 7=8.8 Hz, 2H), 7.30 (dd, 7=8.4, 2.2 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.03 (dd, 7=7.8, 1.6 Hz, IH), 6.87 (d, 7=8.4 Hz, IH), 2.65 (t, 7=7.4 Hz, 2H), 1.66 (sext, 7=7.4 Hz, 2H), 0.94 (t, 7=7.4 Hz, 3H).
Example 55: 2'-Hvdroxv-3'-(N'-ri-f4-methylsulfa]ivl-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidenel-hvdrazinol-biphenyl-3-carboxvlic acid (Compound 155)



(Figure Removed)

This compovmd was prepared as described in Scheme II. 'H NMR (500 MHz, 13.05 (s, IH), 13.03 (s, IH), 9.28 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 7.94 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, .7=7.7,1.7,1.2 Hz, IH), 7.74-7.72 (m, 2H), 7.60 (t, .7=7.7 Hz, IH), 7.49 (d, .7=9.0 Hz, 2H), 7.46 (d, .7=9.0 Hz, 2H), 7.29 (td, 7=7.7, 1.2 Hz, IH), 7.20 (td, .7=7.7, 0.8 Hz, IH), 7.11 (t, ,7=7.8 Hz, IH), 7.00 (dd, .7=7.8, 1.6 Hz, IH), 6.88 (dd, .7=7.7, 0.8 Hz, IH), 2.55 (s, 3H).
Example 56: 2'-Hvdroxv-3'-(N'-[l-(4-methoxvmethvl-phenivl')-2-oxo-1.2-dihvdro-indol-3-vlidenel-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 156)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-G?d) 13.07 (s, IH), 13.03 (s, IH), 9.28 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.74 (m, IH), 7.73 (dd, .7=7.9, 1.6 Hz, IH), 7.60 (t, .7=7.7 Hz, IH), 7.54 (d, .7=9.0 Hz, 2H), 7.52 (d, .7=9.0 Hz, 2H), 7.29 (td, J=7.8, 1.2 Hz, IH), 7.20

(td, .7=7.8, 0.8 Hz, IH), 7.12 (t, .7=7.9 Hz, IH), 7.01 (dd, 7=7.9, 1.6 Hz, IH), 6.90 (dd, .7=7.8, 0.8 Hz, IH), 4.52 (s, 2H), 3.36 (s, 3H).
Example 57: (±)-2'-Hvdroxv-3'-(N'-(2-oxo-l-r4-('2.2.2-triflu.oro-l-hvdroxv-l-methvl-ethvlV phenvl1-1.2-dihvdro-indol-3-vlidenel-hvdrazino)-biphenvl-3-carboxvlic acid (Compound 157)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-4s) 13.06 (s, IH), 13.03 (s, IH), 9.29 (s, IH), 8.12 (s, IH), 7.94 (d, .7=7.6 Hz, IH), 7.83-7.72 (m, 5H), 7.62-7.58 (m, 3H), 7.30 (t, .7=7.9 Hz, IH), 7.21 (t, .7=7.9 Hz, IH), 7.12 (t, J=7.8 Hz, IH), 7.01 (d, .7=7.8 Hz, IH), 6.93 (d, .7=7.9 Hz, IH), 6.77 (s, IH), 1.76 (s, 3H).
Example 58: 3'-(N'-r5-Fluoro-l-(4-methvl-3-trifluoromethyl-phenylV2-oxo-1.2-dihydro-indol-3-ylidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 158)
(Figure Removed)
This compound was prepared as described in Scheme H !H NMR (500 MHz, DMSO-40 13-07 (s, IH), 13.03 (s, IH), 9.37 (s, IH), 8.12 (s, IH), 7.94 (d, ,7=7.6 Hz, IH), 7.88 (s,
IH), 7.81-7.75 (m, 3H), 7.68 (d, J=8.1 Hz, IH), 7.63-7.57 (m, 2H), 7.15-7.09 (m, 2H), 7.04 (d, J=7.6 Hz, IH), 6.93 (m, IH), 2.54 (s, 3H).
Example 59: 2'-Hvdroxy-3'-(N'-(2-oxo-l-r4-(2.2.2-trifluoro-l-methoxv-l-methvl-ethvl)-phenvn-1.2-dihvdro-indol-3-vlidenej-hvdrazino)-bit)henvl-3-carboxvlic acid (Compound 159)
(Figure Removed)
This compound was prepared as described in Scheme H. 'H NMR (500 MHz, 13.05 (s, IH), 13.02 (s, IH), 9.29 (s, IH), 8.12 (s, IH), 7.94 (d, .7=7.8 Hz, IH), 7.81-7.72 (m, 5H), 7.68-7.65 (m, 2H), 7.60 (t, 7=7.8 Hz, IH), 7.31 (t, .7=7.6 Hz, IH), 7.22 (t, .7=7.6 Hz, IH), 7.12 (t, J=7.9 Hz, IH), 7.03 (d, J=7.8 Hz, IH), 6.99 (d, .7=7.8 Hz, IH), 3.24 (s, 3H), 1.85 (s, 3H).
Example 60: 3'-IN'-[l-(3.4-Diniethvl-phenvlV6-fluoro-2-oxo-1.2-dihvdro-indol-3-ylidenel-hvdrazino}"2'-hvdroxv-bihenvl-3-carboxvlic acid (Comound 160)

(Figure Removed)
This compound was prepared as described in Scheme DC. 'H NMR (500 MHz, DMSO-ck) 13.03 (s, IH), 12.99 (s, IH), 9.27 (s, IH), 8.12 (t, .7=1.5 Hz, 1H)S 7.94 (ddd, 7=7.7,1.5,

1.2 Hz, IH), 7.79 (ddd, .7=7.7, 1.5, 1.2 Hz, IH), 7.74 (dd, .7=8.4, 5.3 Hz, IH), 7.72 (dd, .7=7.8, 1.4 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.36 (d, 7=8.0 Hz, IH), 7.31 (d, J=1.8 Hz, IH), 7.25 (dd, 7=7.8, 1.8 Hz, IH), 7.11 (t, 7=7.8 Hz, IH), 7.03-6.98 (m, 2H), 6.66 (dd, J=9.3, 2.2 Hz, IH), 2.31 (s, 3H), 2.30 (s, 3H).
Example 61: 3'-(N'-[6-Fluoro-l-(4-isopropvl-phenyl)-2-oxo-1.2-dihvdro-mdol-3-vlidene1-hvdrazinol -2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 161)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-d6) 13.02 (s, IH), 12.98 (s, IH), 9.28 (s, IH), 8.11 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.8, 1.6, 1.1 Hz, IH), 7.79 (m, IH), 7.75 (dd, 7=7.7,4.9 Hz, IH), 7.73 (dd, 7=7.8, 1.5 Hz, IH), 7.59 (t, 7=7.8 Hz, IH), 7.48 (d, 7=9.2 Hz, 2H), 7.46 (d, 7=9.2 Hz, 2H), 7.11 (t, 7=7.8 Hz, IH), 7.02 (m, IH), 7.00 (dd, 7=7.8,1.5 Hz, IH), 6.69 (dd, 7=9.3, 2.2 Hz, IH), 3.01 (sept, 7=6.9 Hz, IH), 1.27 (d, 7=6.9 Hz, 6H).
Example 62: 3'-(N'-[l-(3.4-Dimethvl-phenvl)2-oxo-5-trifluoromethvl-1.2-dtti.vdro-mdol-3-vlidene]-hydrazino}-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 162)

(Figure Removed)

This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSQ-dt) 13.12 (s, IH), 12.99 (s, IH), 9.38 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 8.03 (m, IH), 7.94 (ddd, .7=7.8, 1.6,1.1 Hz, IH), 7.85 (dd, 7=7.8,1.5 Hz, IH), 7.80 (ddd, 7=7.8, 1.6,1.1 Hz, IH), 7.62 (m, IH), 7.60 (t, .7=7.8 Hz, IH), 7.37 (d, .7=8.0 Hz, IH), 7.33 (d,7=1.9 Hz, IH), 7.26 (dd, .7=8.0,1.9 Hz, IH), 7.13 (t,7=7.8 Hz, IH), 7.05 (dd, .7=7.8, 1.5 Hz, IH), 7.01 (d, .7=8.3 Hz, IH), 2.32 (s, 3H), 2.31(s,3H).
Example 63: 3'-{N'-[6-Fluoro-2-oxo-l-(4-propvl-phenvlV1.2-dihydro-indol-3-vlidene]-hvdrazino)-2'-hvdro7cv-biphenvl-3-carboxvlic acid (Compound 163)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-4) 12.98 (s, IH), 9.28 (s, IH), 8.11 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.75 (dd, 7=7.5, 4.7 Hz, IH), 7.72 (dd, 7=7.8, 1.6 Hz, IH), 7.59 (t, 7=7.7 Hz, IH), 7.45 (d, 7=8.5 Hz, 2H), 7.42 (d, 7=8.5 Hz, 2H), 7.11 (t, 7=7.8 Hz, IH), 7.02 (m, IH), 7.00 (dd, 7=7.8, 1.6 Hz, IH), 6.68 (dd, 7=9.4, 2.3 Hz, IH), 2.66 (t, 7=7.4 Hz, 2H), 1.66 (sext, 7=7.4 Hz, 2H), 0.95 (t, 7=7.4 Hz, 3H).

Example 64: 2'-Hvdroxy-3'-{N'-[2-oxo-(4-propvl-phenvlV5 -trifluoromethyl-1.2-dihvdro-indol-3-vlidenel-hvdrazinoi-biphenvl-3-carboxvlic acid (Compound 164)
(Figure Removed)
This compound was prepared as described in Scheme II. JH NMR (500 MHz, DMSO-fiftf) 13.11 (s, IH), 12.99 (s, IH), 9.38 (s, IH), 8.12 (t,7=1.7 Hz, IH), 8.03 (d, 7=1.5 Hz, IH), 7.95 (ddd, 7=7.7,1.7,1.2 Hz, IH), 7.85 (dd, 7=8.2, 1.5 Hz, IH), 7.80 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.62 (m, IH), 7.60 (t, 7=7.7 Hz, IH), 7.46 (d, 7=8.6 Hz, 2H), 7.43 (d, 7=8.6 Hz, 2H), 7.13 (t, 7=7.8 Hz, IH), 7.05 (dd, 7=7.8, 1.6 Hz, IH), 7.02 (d, 7=8.2 Hz, IH), 2.66 (t, 7=7.4 Hz, 2H), 1.67 (sext, 7=7.4 Hz, 2H), 0.95 (t, 7=7.4 Hz, 3H).
Example 65: 3'-(N'-r4.5-Difluoro-l-(4-isopropvl-phenvn-2-o3to-1.2-dihvdro-iadol-3-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 165")

(Figure Removed)
This compound was prepared as described in Scheme II. !H NMR (500 MHz, DMSO-4) 13.25 (s, IH), 13.01 (s, IH), 9.39 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.64 (dd, 7=7.8, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz,

IH), 7.47 (d, .7=8.7 Hz, 2H), 7.43 (d, 7=8.7 Hz, 2H), 7.29 (dt, .7=11.2, 8.5 Hz, IH), 7.14 O, 7=7.8 Hz, IH), 7.05 (dd,7=7.8, 1.6 Hz, IH), 6.65 (dd, 7=8.5, 3.1 Hz, IH), 3.00 (sept, .7=7.0 Hz, IH), 1.27 (d, .7=7.0 Hz, 6H).
Example 66: 2'-Hvdroxv-3'-[N'-(2-oxo-l-piperidin-4-vl-l.2-dihvdro-indol-3-ylidene)-h.vdrazinol-biphenvl-3-carboxvlic acid (Compound 166)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR. (5OO MHz, 13.15 (s, IH), 8.13 (t, 7=1.4 Hz, IH), 7.91 (d, 7=7.8 Hz, IH), 7.68 (d, 7=7.8 Hz, IH), 7.66-7.63 (m, 2H), 7.51 (t, 7=7.8 Hz, IH), 7.38 (d, 7=7.6 Hz, IH), 7.28 (td,7=7.6, 1.0 Hz, IH), 7.11 (t, 7=7.6 Hz, IH), 7.03 (t, 7=7.6 Hz, IH), 6.96 (dd, 7=7.6, 1.5 Hz, IH), 4.42 (m, IH), 3.26 (m, 2H), 2.84 (m, 2H), 2.45 (m, 2H), 1.76 (m, 2H).
Example 67: 3'-IN'-[5-Fluoro-l-f2-fluoro-4-me1:hvl-phenvl)-2-oxo-l.2-dihvdro-indol-3-'vlidene]-hvdrazino)-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 167)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-rftf) 13.05 (s, IH), 13.02 (s, IH), 9.37 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7==7.8, 1.7,

1.3 Hz, IH), 7.79 (m, IH), 7.78 (dd, .7=7.8,1.5 Hz, IH), 7.60 (t, .7=7.8 Hz, IH), 7.58 (dd, .7=8.2, 2.7 Hz, IH), 7.52 (t, .7=8.1 Hz, IH), 7.37 (dd, 7=11.3, 1.2 Hz, IH), 7.25 (dd, .7=8.1,1.2 Hz, IH), 7.13 (t, .7=7.8 Hz, IH), 7.11 (ddd, .7=9.2, 8.7, 2.7 Hz, IH), 7.04 (dd, .7=7.8, 1.5 Hz, IH, 6.72 (ddd, 7=8.7, 4.1,1.0Hz,lH),2.43(s,3H).
Example 68: 2l-Hvdroxv-3'-[N'-(l-methvl-2-oxo-l .2-dihydro-indol-3-vlidene)-hvdrazino]-biohenvl-3-carboxvlic acid (Compound 168)
(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-40 13.05 (s, IH), 13.03 (s, IH), 9.24 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.1 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.1 Hz, IH), 7.68 (dd, 7=7.9,1.6 Hz, IH), 7.63 (dd, 7=7.7, 1.0 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.35 (td, 7=7.7, 1.0 Hz, IH), 7.16-7.12 (m, 2H), 7.09 (t, 7=7.9 Hz, IH), 6.98 (dd, 7=7,9,1.6 Hz, IH), 3.28 (s, 3H).
Example 69: 3'-[N'-(1-Cyclopentyl-2-oxo-1.2-dihydro-indol-3-vlidene)-hvdrazino]-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 169)
(Figure Removed)
This compound was prepared as described in Scheme n. JH NMR (500 MHz, DMSO-d,,) 13.12 (s, IH), 13.00 (s, IH), 9.23 (s, IH), 8.13 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.8, 1.7, 1.1 Hz, IH), 7.79 (ddd, 7-7.6, 1.7,1.1 Hz, IH), 7.68 (dd, 7=7.8, 1.6 Hz, IH), 7.65 (dd, 7=7.6, 1.1 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.32 (td, 7=7.6,1.1 Hz, IH), 7.21 (dd, 7=7.6, 0.8 Hz, IH), 7.13 (td,
7=7.6, 0.8 Hz, IH), 7.09 (t, 7=7.8 Hz, IH), 6.98 (dd, 7=7.8, 1.6 Hz, IH), 4.76 (qn, 7=8.5 Hz, IH), 2.10 (m, 2H), 1.97-1.89 (m, 4H), 1.68 (m, 2H).
Example 70: 3'-{N-ri-CS(-Dimethvl-phenvll-e-methvl^-oxo-l^-dihydro-indol-S-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 170)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (300 MHz, DMSO-4,) 12.98 (s, 2H), 9.22 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.70 (dd, 7=8.0, 1.5 Hz, IH), 7.60 (dd, 7=7.7, 1.6 Hz, IH), 7.59 (t, 7=7.7 Hz, IH), 7.35 (d, 7=8.0 Hz, IH), 7.28 (d, 7=1.9 Hz, IH), 7.21 (dd, 7=8.0,1.9 Hz, IH), 7.10 (t, 7=7.7 Hz, IH), 7.00 (m, IH), 6.98 (dd, 7=7.7, 1.6 Hz, IH), 6.65 (m, IH), 2.31 (s, 6H), 2.30 (s, 3H).
Example 71: 2'-Hvdroxv-3'-['N'-(2-oxo-1 -phenvl-1.2-dihvciro-indol-3-vlideneVhvdrazino1-biphenvl-3-carboxvlic acid (Compound 171)
(Figure Removed)

This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 13.07 (s, IH), 13.04 (s, IH), 9.28 (s, IH), 8.12 (t, 7=1.5 Hz, IH), 7.94 (ddd, 7=7.6, 1.5, 1.1 Hz, IH), 7.79 (ddd, 7=7.6, 1.5, 1.1 Hz, IH), 7.76-7.72 (m, 2H), 7.61 (td, 7=7.4, 1.0 Hz, 2H),
7.60 (t, .7=7.6 Hz, IH), 7.55 (dd, .7=7.4, 1.0 Hz, 2H), 7.50 (tt, .7=7.4, 1.0 Hz, IH), 7.3O (td, .7=7.6, 1.1 Hz, IH), 7.20 (td, .7=7.6, 0.6 Hz, IH), 7.12 (t, .7=7.8 Hz, IH), 7.01 (dd, .7=7.8,1.5 Hz, IH), 6.89 (d, .7=7.6 Hz, IH)
Example 72: 3'-[N'-(6-Fluoro-2-oxo-l -phenvl-2.3-dihvdro-lH-indol-3-vl)-hvdrazino1-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 1721
(Figure Removed)
This compound was prepared as described in Scheme n. *H NMR (500 MHz, DMSO-d«) 13.04 (s, IH), 12.98 (s, IH), 9.30 (s, IH), 8.12 (t, .7=1.5 Hz, IH), 7.94 (ddd, .7=7.7, 1.5, 0.9 Hz, IH), 7.79 (ddd, .7=7.7, 1.5, 0.9 Hz, IH), 7.76 (dd, .7=8.5, 5.7 Hz, IH), 7.73 (dd, .7=7.8, 1.2 Hz, IH), 7.64-7.55 (m, 5H), 7.51 (t, .7=7.3 Hz, IH), 7.11 (t, .7=7.8 Hz, IH), 7.05-6.99 (m, 2H), 6.71 (dd, 7=9.4,2.2 Hz, IH).
Ie73: 3'-IN'-[l-(3.4-Dimethvl-phenvn-6-isopropvl-2-oxo-1.2-dihydro-indol-3-vlidene1-}-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 173)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (300 MHz, DMSO-dtf) 13.03 (s, IH), 13.00 (s, IH), 9.23 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, 7=7.8, 1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.8, 1.6, 1.2 Hz, IH), 7.70 (dd, 7=7.8, 1.6 Hz, IH), 7.64 Cd, 7=7.9 Hz,

IH), 7.59 (t, .7=7.8 Hz, IH), 7.36 (d, 7=8.0 Hz, IH), 7.29 (d, 7=2.0 Hz, IH), 7.23 (dd, .7=8.0, 2.0 Hz, IH), 7.10 (t, 7=7.8 Hz, IH), 7.08 (dd, 7=7.9, 1.2 Hz, IH), 6.98 (dd, 7=7.8, 1.6 Hz, IH), 6.68 (d, 7=1.2 Hz, IH), 2.89 (sept, 7=6.8 Hz, IH), 2.31 (s, 3H), 2.31 (s, 3H), 1.17 (d, 7=6.8 Hz, 6H).
Example 74: 3'- IN'-f 1 -(3.4-Dimethvl-phenyl1-4-isopropvl-2-oxo-l .2-dihvdro-indol-3-vlidene]-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 1741
(Figure Removed)
This compound was prepared as described in Scheme II. 1H KTMR (300 MHz, 13.29 (s, IH), 8.13 (s, IH), 7.94 (d, 7=7.6 Hz, IH), 7.76 (d, 7=7.6 Hz, IH), 7.61-7.54 (m, 2H), 7.35 (d, 7=8.3 Hz, IH), 7.28 (m, IH), 7.22 (m, 2H), 7.16-7.10 (m, 2H), 6.98 (dd, 7=7.6, 1.1 Hz, IH), 6.65 (d, 7=7.6 Hz, IH), 3.99 (m, IH), 2.31 (s, 3H), 2.30 (s, 3H), 1.3 8 (d, 7=6.9 Hz, 6H).
Example 75: 3'-(N'-['l-(3.4-Dimethvl-phenvl)-2-oxo-6-trifluoromethyl-1.2-dihydro-indol-3-vlidene]-hvdrazinoV-4-fluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 17 51
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NTMR (500 MHz, DMSO-dtf) 13.22 (s, IH), 9.44 (s, IH), 8.01 (dd, 7=7.0, 2.4 Hz, IH), 7.92 (d, 7=7.8 Hz, IH), 7.78
(dd, 7=7.8, 1.5 Hz, IH), 7.78 (m, IH), 7.54 (d, 7=7.8 Hz, IH), 7.41 (dd, 7=10.4, 8.4 Hz, IH), 7.39 (d, 7=7.9 Hz, IH), 7.33 (d, 7=1.9 Hz, IH), 7.27 (dd, 7=7.9,1.9 Hz, 1H),7.13 (t, 7=7.8 Hz, 1H),7.05 (dd, 7=7.8,1.5 Hz, IH), 6.96 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 76: 5'-Chloro-3'- {N'-[ 1-(3.4-dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene]-hvdrazino-4-fluoro-2'-hvdroxv-biphenyl-3-carboxylic acid (Compound 176)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NVIR (300 MHz, DMSO-cf,,) 13.38 (s, IH), 13.11 (s, IH), 9.70 (s, IH), 8.02 (d, 7=8.0 Hz, 1 H), 8.02 Cdd, 7=6.9, 2.4 Hz, IH), 7.80 (ddd, 7=8.5, 4.6, 2.4 Hz, IH), 7.76 (d, 7=2.6 Hz, IH), 7.54 (d, 7=8.0 Hz, IH), 7.42 (dd, 7=10.7, 8.5 Hz, IH), 7.39 (d, 7=7.9 Hz, IH), 7.33 (d, 7=2.0 Hz, IH), 7.27 (dd, J=7.9, 2.0 Hz, IH), 7.08 (d, 7=2.6 Hz, IH), 6.95 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 77: 3'-(N'-[1(3.4-Dimethvl-phenvn-2-oxo-6-trifluoromethyl-l .2-dihvdro-indol-3-vlidene1-hvdrazino}-6-fluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound
(Figure Removed)
This compound was prepared as described in Scheme H 'H N1MR (300 MHz, DMSO-4) 13.19 (s, IH), 13.13 (s, IH), 9.56 (s, IH), 7.98 (m, IH), 7.92 (d, 7=7.8 Hz, IH), 7.82
(dd, 7=7.7, 1.1 Hz, IH), 7.54 (d, .7=7.8 Hz, IH), 7.44 (m, IH), 7.38 (d, 7=8.0 Hz, IH), 7.33 (d, .7=1.7 Hz, IH), 7.26 (dd, .7=8.0, 1.7 Hz, IH), 7.11 (t, .7=7.7 Hz, IH), 7.00 (dd, 7=7.7, 1.1 Hz, IH), 6.95 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 78: 3'-{N'l-(3.4-Dim.ethvl-phenvl)-4.S-difluoro-2-oxo-1.2-dih.vdro-indol-3-vlidenel-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 178")

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, 13.27 (s, IH), 13.05 (s, IH), 9.40 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.94 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.64 (dd, 7=7.9, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.36 (d, 7=8.2 Hz, IH), 7.29 (dt, 7=11.1, 8.5 Hz, IH), 7.29 (d, 7=2.1 Hz, IH), 7.22 (dd, 7=8.2, 2.1 Hz, IH), 7.14 (t, 7=7.9 Hz, IH), 7.05 (dd, 7=7.9,1.6 Hz, IH), 6.63 (dd, 7=8.5, 3.2 Hz, IH), 2.31 (s, 3H), 2.29 (s, 3H).
Example 79: 3'- (N'-[ 1 -(3.4-Dimethvl-phenyl)-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3 -vlidenel-hvdrazino) -2'-hvdroxv-3 -methvl-biphenvl-4-carboxvlic acid (Compound 179)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dt) 13.23 (s, IH), 12.83 (s, IH), 9.43 (s, IH), 7.92 (d, 7=7.9 Hz, IH), 7.91 (d, 7=7.9 Hz, IH), 7.78 (dd, .7=7.8,1.5 Hz, IH), 7.54 (d, 7=7.9 Hz, IH), 7.49 (s, IH), 7.46 (d, 7=7.9 Hz, IH), 7.39 (d, J=7.9 Hz, IH), 7.33 (d, 7=1.8 Hz, IH), 7.27 (dd, 7=7.9,1.8 Hz, IH), 7.13 (t, 7=7.8 Hz, IH), 7.05 (dd, 7=7.8,1.6 Hz, IH), 6.96 (s, IH), 2.59 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H).
Example 80: 3'-IN'-ri-(3.4-Dimethvl-phenvl)-2-oxo-6-trifluoromethvl-2.3-dihvdro-lH-indol-3-vl1-hvdrazinol-2-fluoro-2'-hvdroxv-biphenvl-4-carboxvlic acid (Compound 180)


(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-ck) 13.31 (s, IH), 13.19 (s, IH), 9.58 (s, IH), 7.93 (d, 7=7.9 Hz, IH), 7.85 (dd, 7=7.8, 1.5 Hz, IH), 7.82 (dd, 7=7.8, 1.5 Hz, IH), 7.75 (dd, 7=10.4, 1.5 Hz, IH), 7.58 (t, 7=7.8 Hz, IH), 7.54 (d, 7=7.9 Hz, IH), 7.38 (d, 7=8.0 Hz, IH), 7.33 (d, 7=1.9 Hz, IH), 7.27 (dd, 7=8.0,1.9 Hz, IH, 7.12 (t, 7=7.8 Hz, IH), 6.99 (dd, 7=7.8,1.5 Hz, IH), 6.95 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 81: 3'-(N'-ri-(3.4-raethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethvl-2.3-dihvdro-lH-indol-3-vl1-hvdrazinol-4-fluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 181)


(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-40 13.36 (s, IH), 8.00 (dd, .7=6.9, 2.1 Hz, IH), 7.78 (m, IH), 7.66 (dd, .7=7.7, 1.4 Hz, IH), 7.50 (d, .7=9.5 Hz, IH), 7.41 (m, IH), 7.39 (d, .7=8.1 Hz, IH), 7.32 (d, J=1.6 Hz, IH), 7.26 (dd, 7=8.1, 1.6 Hz, IH), 7.14 (t, 7=7.7 Hz, IH), 7.07 (dd, .7=7.7, 1.4 Hz, IH), 6.80 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 82: 5'-Chloro-3'-{N'-ri-(3.4-dimethvl-phenvl)-4-fluoro-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3 -vlidenej-hydrazinol -4-fluoro-2'-hydroxv-biphenyl-3-carbQxvlic acid (Compound 182

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-4) 13.38 (s, IH), 13.22 (s, IH), 9.78 (s, IH), 8.01 (dd, 7=7.0,2.3 Hz, IH), 7.80 (ddd, 7=8.6, 4.2, 2.3 Hz, IH), 7.55 (d, 7=2.5 Hz, IH), 7.51 (d, 7==9.5 Hz, IH), 7.42 (dd, 7=10.5, 8.6 Hz, IH), 7.38 (d, 7=8.0 Hz, IH), 7.31 (d, 7=1.6 Hz, IH), 7.25 (dd, 7=8.0, 1.6 Hz, IH), 7.10 (d, 7=2.5 Hz, IH), 6.80 (s, IH), 2.32 (s, 3H), 2.30 (s, 3H).
Example 83: 3-[(3'-Carboxy-2-hvdroxy-biphenyl-3-vl)-hvdrazono1-l-(3.5-dimethvl-phenyl)-2-oxp-2.3-dihvdro-lH-indQle-6-carboxylic acid methyl ester (Compound 183)

(Figure Removed)
This compound was prepared as described in Scheme n. ]H NMR (500 MHz, DMSO-A) 8 13.26 (s, IH), 13.05 (s, IH), 9.42 (s, IH), 8.12 (t, J = 1.6 Hz, IH), 7.95 Cddd, J = 7.7,1.6,1.2 Hz, IH), 7.86 (d, J= 7.9 Hz, IH), 7.81 (dd, J = 7.9,1.4 Hz, IH), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, IH), 7.77 (dd, J = 7.8,1.6 Hz, IH), 7.61 (t, J = 7.7 Hz, IH), 7.29 (d, .7= 1.4 Hz, IH), 7.18 (s, IH), 7.16 (s, 2H), 7.14 (t, J= 7.8 Hz, IH), 7.06 (dd, J = 7.8,1.6 Hz, IH), 3.83 (s, 3H), 2.38 (s, 6H).
Example 84: 3-[(3'-Carboxy-4'-fluoro-2-hvdroxv-biphenyl-3-vl)-hvdrazono1-l-(3.5-dim.ethvl-phenvlV2-oxo-2.3-dihvdro-lH-indole-6-carboxvlic acid methyl ester (Compound 184)



(Figure Removed)
This compound was prepared as described in Scheme II. :H NMR (500 MHz, 813.35 (s, IH), 13.24 (s, IH), 9.43 (s, IH), 8.01 (dd, /= 7.2, 2.6 Hz, IH), 7.85 (d, J = 7.9 Hz, IH), 7.81 (dd, J= 7.9,1.3 Hz, IH), 7.79 (m, IH), 7.77 (dd, J= 7.8,1.6 Hz, IH), 7.42 (dd, J = 10.7, 8.5 Hz, IH), 7.28 (d, J = 1.3 Hz, IH), 7.18 (s, IH), 7.16 (s, 2H), 7.13 (t, J= 7.8 Hz, IH), 7.05 (dd, J= 7.8, 1.6 Hz, IH), 3.83 (s, 3H), 2.37 (s, 6H).
Example 85: 3-[(3'-Carboxy-4'-fluoro-2-hvdroxv-biphenvl-3-yl)-hvdrazono1-l-(3.4-dimethyl-phenvl)-2-oxo-2.3-dihvdro-lH-indole-6-carboxvlic acid methvl ester (Compound 185)
(Figure Removed)
This compound was prepared as described in Scheme II H NMR (500 MHz, DMSO-dtf) 8 13.34 (s, IH), 13.24 (s, IH), 9.43 (s, IH), 8.01 (dd, ,7= 7.1, 2.1 Hz, IH), 7.85 (d, J = 1.9 Hz, IH), 7.81 (m, IH), 7.79 (m, IH), 7.77 (m, IH), 7.41 (dd, J = 10.5, 8.8 Hz, IH), 7.39 (d, J= 8.0 Hz, IH), 7.32 (d, J= 1.8 Hz, 1H)S 7.27 (d, J = 1.0 Hz, IH), 7.26 (m, IH), 7.13 (t, ,7= 7.8 Hz, IH), 7.05 (dd, J= 7.8,1.6 Hz, IH), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H).
Example 86: 3-r(3'-Carboxv-5-chloro-4'-fluoro-2-hvdroxv-biphenvl-3-vl)-hvdra2ono1-l-(3.5-dime1hvl-phenvl)-2-oxo-2.3-dihvdro4H-indole-6-carboxvlic acid methyl ester (Compound 186)

(Figure Removed)
This compound was prepared as described in Scheme EL 'H NMR (500 MHz, CD3OD- d4,) 8 8.05 (dd, J= 6.7, 1.2 Hz, IH), 7.89-7.81 (m, 2H), 7.75-7.70 (m, 2H), 7.40 (s, IH), 7.29 (dd, 7 = 10.3, 8.7 Hz, IH), 7.18 (s, IH), 7.09 (s, 2H), 6.97 (d, /= 1.7 Hz, IH), 3.86 (s, 3H), 2.41 (s, 6H).
Example 87: 3t-(N'-ri-f2-Cvano-thiophen-3-ylV2-oxo-1.2-dihvdro-mdol-3-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-cafboxvlic acid (Compound 187)

(Figure Removed)
This compound was prepared as described in Scheme II. ]H NMR (500 MHz, CD3OD- rf,) 8 8.05 (t, J= 1.5 Hz, IH), 8.03 (d, J= 5.3 Hz, IH), 7.89 (ddd, J= 7.7,1.5,1.0 Hz, IH), 7.74 (ddd, /= 7.6, 1.1, 0.6 Hz, IH), 7.73 (dd, J = 7.8, 1.6 Hz, IH), 7.56 (ddd, J= 7.7, 1.5, 1.0 Hz, IH), 7.41 (t, J= 7.7 Hz, IH), 7.37 (d, J= 5.3 Hz, IH), 7.28 (td, J = 7.6, 1.1 Hz, IH), 7.20 (td, / =

7.6,0.8 Hz, IH), 7.03 (t, J= 7.8 Hz, IH), 6.97 (dd, J = 7.8,1.6 Hz, IH), 6.93 (ddd, J = 7.8, 0.8, 0.6 Hz, IH).
Example 88: 2'-Hvdroxv-3'-rN'-(2-oxo-l-thiophen-3-vl-1.2-dihvdro-indol-3-vlidene)-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 188)
(Figure Removed)
This compound was prepared as described in Scheme II. !H NMR (500 MHz, CD3OD- dj) S 8.15 (t, J = 1.6 Hz, IH), 7.99 (ddd, J = 7.7, 1.6, 1.2 Hz, IH), 7.74 (dd, J = 7.8, 1.6 Hz, IH), 7.73 (m, IH), 7.71 (ddd, J= 7.7, 1.6, 1.2 Hz, IH), 7.65-7.62 (m, 2H), 7.52 (t, J= 7.7 Hz, IH), 7.33 (dd, J= 3.9, 2.7 Hz, IH), 7.28 (td, J = 7.6, 1.2 Hz, IH), 7.18 (td, J = 7.6, 0.8 Hz, IH), 7.07 (t, .7= 7.8 Hz, IH), 7.04 (d, J =7.6 Hz, IH), 6.98 (dd, 7=7.8, 1.6 Hz, IH).
Example 89: 3-[(3'-Carboxv-2-hydroxv-biphenvl-3-vl)-hvdrazono]-l-(3.-4-dimethvl-phenvl)-2-oxo-2.3-dihvdro-lH-indole-6-carboxvlic acid methyl ester (Compound

(Figure Removed)
This compound was prepared as described in Scheme 31. *H NMR (500 MHz, 8 13.25 (s, IH), 13.05 (s, 1H), 9.42 (s, IH), 8.12 (t, J = 1.6 Hz, IH), 7.95 (ddd, J= 7.8, 1.6,1.2 Hz, IH), 7.85 (dJ= 8.0 Hz, IH), 7.81 (dd,/= 8.0,1.4 Hz, IH), 7.79 (ddd, .7= 7.8,1.6,1.2 Hz, IH), 7.77 (dd, J= 7.9, 1.6 Hz, IH), 7.60 (t, J= 7.8 Hz, IH), 7.39 (d, / = 8.0 Hz, IH), 7.32 (d, J = 2.0 Hz, IH), 7.28 (d, J = 1.4 Hz, IH), 7.26 (dd, J = 8.0, 2.0 Hz, IH), 7.14 (t, J= 7.9 Hz, IH), 7.06 (dd, J = 7.9,1.6 Hz, IH), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H).

Example 90: 3'-IN'-|'l-(4-Chloro-3-trifluoromethvl-phenvlV6-cvano-2-oxo-1.2-dihydro-indol-3-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 1901

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR C500 MHz, DMSO-4) 8 13.20 (s, IH), 13.02 (s, IH), 9.49 (s, IH), 8.12 (t,J= 1.7 Hz, IH), 8.11 (d,.7= 2.4 Hz, IH), 7.98 (d, /= 8.5 Hz, IH), 7.95 (ddd, J = 7.7, 1.7, 1.3 Hz, IH), 7.94 (dd, J= 8.5, 2.4 Hz, IH), 7.90 (d,J= 7.8 Hz, IH), 7.79 (dd,/= 7.8,1.6 Hz, IH), 7.79 (m, IH), 7.66 (dd, 7= 7.8,1.3 Hz, IH), 7.60 (t, J= 7.7 Hz, IH), 7.51 (d, J= 1.3 Hz, IH), 7.15 (t, /= 7.8 Hz, IH), 7.09 (dd, J= 7.8,1.6 Hz, IH).
Example 91: 5'-Chloro-3'- (N'-[6-cvano-l -f4-isopropvl-phenvl')-2-oxo-l .2-dihvdro-indol-3 -vlidene]-hvdrazino}-4-fluoro-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 191)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR C500 MHz, 5 13.37 (s, IH), 13.14 (s, IH), 9.74 (s, 1H)3 8.01 (dd, J= 7.0, 2.4 Hz, IH), 7.99 (d, J = 7.8 Hz, IH), 7.80 (ddd, J= 8.5,4.6, 2.4 Hz, IH), 7.77 (d, J= 2.6 Hz, IH), 7.64 (dd, J= 7.8, 1.3 Hz, IH), 7.49 (d,J = 9.1 Hz, 2H), 7.47 (d, J= 9.1 Hz, 2H), 7.42 (dd,.7= 10.7, 8.5 Hz, IH), 7.24 (d,/= 1.3 Hz, IH), 7.09 (d, J= 2.6 Hz, IH), 3.01 (sept, J= 6.9 Hz, IH), 1.28 (d, J= 6.9 Hz, 6H).

Example 92: 3'-(N'-r6-Cvano-l-(4-isoDroDvl-phenl)-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-4-fluoro-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 192)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, CD3OD- d4) 8 7.91 (dd, /= 6.8, 2.4 Hz, IH), 7.81 (d, J = 7.8 Hz, IH), 7.73 (dd, J= 7.7, 1.6 Hz, IH), 7.62 (ddd, J= 8.5,4.6, 2.4 Hz, IH), 7.48 (d, J- 8.4 Hz, 2H), 7.47 (m, IH), 7.40 (d, J= 8.4 Hz, 2H), 7.21 (dd, .7= 10.3, 8.5 Hz, IH), 7.09 (d, J = 1.0 Hz, IH), 7.05 (t, /= 7.7 Hz, IH), 7.00 (dd, J = 7.7,1.6 Hz, IH), 3.02 (sept, J= 6.9 Hz, IH), 1.32 (d, J= 6.9 Hz, 6H).
Example 93: (+)l-f3.4-Dimethvl-phenvlV3-(r2-hvdroxv-3l-f2.2.2-trifluoro-l-hvdroxv-ethvlV biphenyl-3-vl1-hvdrazono-6-methanesulfonvl-1.3-dihvdro-indol-2-one (Compound 193)
(Figure Removed)
This compound was prepared as described in Schenxe II. 'H NMR (500 MHz, CD3OD- fc) 5 7.88 (d, J= 7.7 Hz, IH), 7.78 (d, 7= 7.7 Hz, IH), 7.65 (s, IH), 7.58 (m, IH), 7.53-7.44 (m, 3H), 7.37 (d, J = 8.0 Hz, IH), 7.25 (s, IH), 7.19 (d, J= 8.0 Hz, IH), 7.09 (t, J= 7.5 Hz, IH), 7.01 (d, J = 7.5 Hz, IH), 6.99 (s, IH), 5.10 (q, J= 7.0 Hz, IH), 2.37 (s, 3H), 2.37 (s, 3H).
Example 94: 3'- N-r6-Cvano-1 -(4-isopropvl-phenvl)-2-oxo-1.2-dihvdro-indol-3 -ylidenel-hvdrazino\-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 194)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, CD3OD- d4) 5 8.06 (s, IH), 7.90 (d, J = 7.8 Hz, IH), 7.78 (m, IH), 7.71 (d, J = 7.8 Hz, IH), 7.62 (m, IH), 7.44 (m, 2H), 7.40 (d, J= 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.04 (s, IH), 7.00 (t, J = 7.6 Hz, IH), 6.95 (d, J= 7.6 Hz, IH), 2.94 (sept, J = 7.0 Hz, IH), 1.23 (d, J = 7.0 Hz, 6H).
Example 95: 3'-{N'-ri-(3.4-Dimethvl-phenvl)-5-nitro-2-oxo-1.2-dihydro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-birhenvl-3-carboxvlic acid (Compound 195)


(Figure Removed)
This compound was prepared as described in Scheme H *H NMR (500 MHz, DMSO-40 8 13.10 (s, 1H)5 12.93 (s, IH), 8.47 (d, J= 2.3 Hz, IH), 8.16 (dd, J= 8.7, 2.3 Hz, IH), 8.10 (t, J- 1.6 Hz, IH), 7.93 (ddd, J= 7.7, 1.6, 1.2 Hz, IH), 7.85 (dd, J= 7.8, 1.7 Hz, IH), 7.78 (ddd, J= 7.7,1.6,1.2 Hz, IH), 7.58 (t, J= 7.7 Hz, IH), 7.36 (d, J= 8.0 Hz, IH), 7.32-7.21 (m, 2H), 7.12 (t, J= 7.8 Hz, IH), 7.05 (dd, J= 7.8, 1.7 Hz, IH), 6.99 (d, J= 8.7 Hz, IH), 2.30 (s, 3H), 2.28 (s, 3H).

Example 96: 3'-(N'-ri-(3.4-Dimethvl-phenvl')-6-methanesulfonvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 196)


(Figure Removed)
This compound was prepared as described in Scheme II. 1H NMR (500MHz, CD3OD-d,) 5 8.43 (s, 2H), 8.11 (t, J= 1.2 Hz, IH), 7.94 (dt,/= 7.6, 1.2 Hz, IH), 7.71 (dd,/= 7.8, 1.6 Hz, IH), 7.69 (dd, J= 7.4, 0.9 Hz, IH), 7.66 (dt, J= 7.6, 1.2 Hz, IH), 7.47 (t, J= 7.6 Hz, IH), 7.30 (d, J= 8.1 Hz, IH), 7.22-7.18 (m, 2H), 7.14 (dd, J= 7.9, 2.0 Hz, IH), 7.12 (m, IH), 7.03 (t, J = 7.8 Hz, IH), 6.94 (dd, J = 7.8,1.6 Hz, IH), 6.81 (d, J= 7.8 Hz, IH), 3.30 (s, 3H), 2.31 (s, 6H).
Example 97: S'-IN'-re-Cvano-l-CS-dimethyl-phenyD-oxo-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 197)
(Figure Removed)
This compound was prepared as described in Scheme n. !H NMR (500 MHz, DMSO-dtf) 88.25 (d, J = 7.8 Hz, IH), 8.22 (t, J= 1.5 Hz, IH), 7.87-7.82 (m, 2H), 7.51 (t, J = 7.8 Hz, IH), 7.41 (dd, J = 7.7,1.3 Hz, IH), 7.31-7.26 (m, 2H), 7.22 (d, /= 1.9 Hz, IH), 7.15 (dd, J = 7.9,1.9 Hz, IH), 6.99 (dd,J= 7.6,1.5 Hz, IH), 6.92-6.88 (m, 2H), 2.27 (s, 6H).
Example 98:
2l-hydroxY-birhenyl-3 -carboxvlic acid (Compound 1981

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (300 MHz, 8 8.91 (m, IH), 8.85 (m, 0.5H), 8.72 (m, 0.5H), 8.43 (t, J = 2.0 Hz, 0.5H), 8.30 (t, / = 2.1 Hz, 0.5H), 8.06 (m, 0.5H), 8.02 (t, J = 1.5 Hz, 0.5H), 7.90 (t, /= 1.6 Hz, 0.5H), 7.73 (m, 0.5H), 7.72-7.53 (m, 3H), 7.37 (t, J = 7.6 Hz, 0.5H), 7.30 (t, J= 7.7 Hz, 0.5H), 7.12 (m, IH), 7.03 (m, 0.5H), 6.95-6.61 (m, 3.5H).
Example 99: 3'-[N'-(l-Furan-3-vl-2-oxo-1.2-dihvdro-indol-3-vlideneVhvdrazino1-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 199)

(Figure Removed)
This compound was prepared as described in Scheme n. JH NMR (500 MHz, CD3OD-^) 8 8.07 (s, IH), 7.90 (m, 2H), 7.66-7.59 (m, 4H), 7.42 (t, J = 7.7 Hz, IH), 7.21 (t, J = 7.6 Hz, IH), 7.09 (t, J= 7.6 Hz, IH), 7.01 (d, J = 7.6 Hz, IH), 6.97 (t, J= 7.6 Hz, IH), 6.88 (dd, J = 7.6,1.3 Hz, IH), 6.74 (dd, .7=2.0,0.7 Hz, IH).

Example 100: 3'-rN'-(l-Benzori.31dioxol-5-vl-2-oxo-1.2-dihvdro-indol-3-vlidene')-hvdrazmo1-2'-hvdroxv-biphenvi-3-carboxvlic acid (Compound 200)



(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dt) 513.02 (s, IH), 8.09 (t, /= 1.6 Hz, IH) ,7.92 (ddd, .7 = 7.7, 1.6,1.2 Hz, IH), 7.76 (ddd, J = 7.7, 1.6, 1.2 Hz, IH), 7.70 (dd, J= 7.8, 1.6 Hz, IH), 7.70 (m, IH), 7.57 (t, J= 7.7 Hz, IH), 7.27 (td,y=7.7, 1.1 Hz, IH), 7.16 (t, .7=7.8 Hz, IH), 7.13-7.07 (m, 3HQ, 6.99-6.96 (m, 2H), 6.82 (d,J= 8.1 Hz, IH), 6.13 (s, 2H). Mixture ~ 90:10
Example 101: 2'-Hvdroxv-3'-{Nl-ri-(3-methvl-thiophen-2-vn-2-oxo-L2-dihvdro-indol-3-vlidenel-hvdrazinoi-biphenvl-3-carboxvlic acid (Compound 201)


(Figure Removed)
This compound was prepared as described iix Scheme n. 1H NMR (500 MHz, DMSO-4) 8 12.94 (s, IH), 8.10 (s, IH), 7.92 (d, J = 7.6 Hz, IH), 7.79-7.69 (m, 3H), 7.63-7.54 (m, 2H), 7.30 (t, J= 7.6 Hz, IH), 7.20 (t, J= 7.6 Hz, IH), 7.14-7.06 Cm, 2H), 6.99 (d, .7= 7.4 Hz, IH), 6.73 (d, J = 7.6 Hz, IH), 2.01 (s, 3H).


Example 102: 2'-Hvdroxy-3'-[N'-(2-oxo-l-thiophen-2-vl-1.2-dihvdro-indol-3-vlideneV hvdrazino]-biphenvl-3-carboxvlic acid (Compound 202)


(Figure Removed)
This compound was prepared as described in Scheme II. 'H NJMR (300 MHz, 8 12.96 (s, IH), 9.33 (s, IH), 8.11 (s, IH), 7.93 (d, J= 7.6 Hz, IH), 7.78 (d, J = 7.6 Hz, IH), 7.74-7.69 (m, 2H), 7.63 (dd,J= 5.5, 1.4 Hz, IH), 7.58 (t, J= 7.6 Hz, IH), 7.36-7.28 (m, 2H), 7.25-7.15 (m, 2H), 7.10 (t, J= 7.8 Hz, IH), 7.08 (d,.7= 7.8 Hz, IH), 7.00 (dd,7=7.6, 1.2 Hz, IH),
Example 103: 2'-Hydroxv-3 '• flST-fl -(4-isopropvl-phenyl)-2-oxo-6-trifluoromethyl-1.2-dihydro-indol-3-vlidene]-hvdrazmol-biphenvl-3-carboxylic acid (Compound 203)

(Figure Removed)
This compound was prepared as described in Scheme EL 'H 1SIMR (500MHz, DMSO) 5 13.23 (s, IH), 13.04 (s, IH), 9.43 (s, IH), 8.12 (t, J= 1.6 Hz, IH), 7.95 (ddd, J = 7.7,1.6, 1.2 Hz, IH), 7.93 (d, J= 8.0 Hz, IH), 7.80 (dd, J = 7.7,1.6,1.2 Hz, IH), 7.79 (d, J= 7.6 Hz, IH), 7.78 (dd, J= 7.9, 1.6 Hz, IH), 7.60 (t, J= 7.7 Hz, IH), 7.55 (d, J= 8.0,1.1 Hz, IH), 7.51 (d, J= 8.8 Hz, 2H), 7.48 (d, /= 8.8 Hz, 2H), 7.14 (t, J= 7.9 Hz, IH), 7.06 (dd, .7 = 7.9,1.6 Viz, IH), 7.00 (d, 7 = 1.1 Hz, IH), 3.01 (sept, J= 6.8 Hz, IH), 1.28 (d, J= 6.8 Hz, 6H).

Example 104: 2'-Hvdroxy-3'-(N'-[2-oxo-l-('4-propvl-phenvl)-6-trifluoroTnethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-biphenyl-3-carboxvlic acid (Compound 2041
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 8 13.23 (s, IH), 13.04 (s, IH), 9.43 (s, IH), 8.12 (t, J - 1.6 Hz, IH), 7.95 (d, J = 7.7, 1.6, 1.2 Hz, IH), 7.93 (d, J= 8.0 Hz, IH), 7.80 (dd, /= 7.7, 1.6, 1.2 Hz, IH), 7.78 (dd, /= 7.7, 1.5 Hz, IH), 7.60 (t, J- 7.7 Hz, IH), 7.55 (m, IH), 7.47 (d, J= 8.5 Hz, 2H), 7.44 (d, J= 8.5 Hz, 2H), 7.14 (t, J= 7.7 Hz, IH), 7.06 (dd, J= 7.7,1.5 Hz, IH), 6.98 (m, IH), 2.67 (t, .7=7.4 Hz, 2H), 1.67 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H).
Example 105: S'-IN'-n(-Ethvl-rjhenvD-SJ-difluoro-oxo-l-dihvdro-indol-S-vlidenel-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 2051
(Figure Removed)
This compound was prepared as described in Scheme EL 1H NMR (500MHz, DMSO) 8 13.15 (s, IH), 13.03 (s, IH), 9.40 (s, IH), 8.11 (t, J = 1.6 Hz, IH), 7.94 (d, J= 7.7, 1.6, 1.1 Hz, IH), 7.79 (m, 2H), 7.60 (t, J= 7.7 Hz, IH), 7.48 (dd, J = 7.8, 2.3 Hz, IH), 7.41 (dd, J - 8.3,

1.4 Hz, 2H), 7.36 (d, J= 8.3 Hz, 2H), 7.21 (ddd, J= 11.6, 9.7, 2.3 Hz, IH) 7.13 (t, J= 7.8 Hz, IH),
7.05 (dd,7=7.8, 1.3 Hz, lH),2.69(q,y=7.5 Hz,2H), 1.24 (t,7=7.5 Hz, 3H).
Example 106: 3'-(N'-ri-(3.4-Diinetfavl-phenvn-5.7-difluoTO-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-bihenvl-3-carboxvlic acid (Compoxmd 206)
(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500MHz, DMSO) 8 13.16 (s, IH), 12.99 (s, IH), 9.40 (s, IH), 8.11 (t, J= 1.6 Hz, IH), 7.94 (ddd, J= 7.7,1.6,
1.2 Hz, IH), 7.79 (m, IH), 7.78 (dd, 7= 7.8, 1.5 Hz, IH), 7.60 (t, J= 7.7 Hz, IH), 7.47 (dd, J= 7.7,
2.2 Hz, IH), 7.28 (m, 2H), 7.23-7.17 (m, IH), 7.13 (t, J= 7.8 Hz, IH), 7.05 (dd, J = 7.8, 1.5 Hz,
IH), 2.29 (s, 3H), 2.27 (s, 3H).
Example 107: 3'- (N-rSJ-Difluoro-oxo-l-propvl-phenvlVl .2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 207}
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 8 13.15 (s, IH), 13.03 (s, IH), 9.40 (s, IH), 8.11 (t, J - 1.6 Hz, IH), 7.94 (ddd, J = 7.7, 1.6,
1.2 Hz, IH), 7.79 (m, 2H), 7.60 (t, /= 7.7 Hz, IH), 7.48 (dd, J= 7.8, 2.4 Hz, IH), 7.40 (dd, J= 8.3, 1.7 Hz, 2H), 7.34 (d, J= 8.3 Hz, 2H), 7.21 (ddd, J= 11.6, 9.7, 2.4 Hz, IH), 7.13 (t, /= 7.8 Hz, IH), 7.05 (dd, J= 7.8, 1.6 Hz, IH), 2.64 (t, .7=7.4 Hz, 2H), 1.65 (sext, J= 7.4 Hz, 2H), 0.93 (t, /= 7.4 Hz,3H).
Example 108: 3'-(N'-[5.7-Difluoro-l-(4-isopropYl-phenvl)-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid CComoound 208)
(Figure Removed)
This compound was prepared as described in Scheme n. 1H NMR (500MHz, DMSO) 8 13.15 (s, IH), 13.04 (s, IH), 9.41 (s, IH), 8.11 (t, J= 1.6 Hz, IH), 7.94 (ddd, ,7= 7.7, 1.6,
1.1 Hz, IH), 7.79 (m, IH), 7.78 (dd, J= 7.8,1.7 Hz, IH), 7.60 (t, J= 7.7 Hz, IH), 7.48 (dd, J= 7.8,
2.1 Hz, IH), 7.42 (dd, J= 8.8, 1.4 Hz, 2H), 7.39 (d, J= 8.8 Hz, 2H), 7.21 (ddd, J = 11.8, 9.5, 2.2
Hz, IH), 7.13 (t, /= 7.8 Hz, IH), 7.05 (dd, J = 7.8, 1.7 Hz, IH), 2.98 Csept, J= 6.9 Hz, IH), 1.26
(d,J=6.9Hz,6H).
Example 109: S'-IN'-ri-CS-Dimethvl-phenvn-oxo-e-trifluoromethvl-l-dihvdro-indol-S-vlidene1-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 209)
(Figure Removed)


This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 813.22 (s, IH), 13.02 (s, lH),9.41(s, IH), 8.10 (t, J= 1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.91 (d, 7 =7.9 Hz, IH), 7.79 (dd, 7=7.7, 1.6, 1.2 Hz, IH), 7.76 (dd, J = 7.8, 1.5 Hz, IH), 7.59 (t, J= 7.7 Hz, IH), 7.52 (m, IH), 7.37 (d,7 = 8.0 Hz, IH), 7.31 (m, IH), 7.25 (dd, 7 = 8.0,1.9 Hz, IH), 7.12 (t, 7= 7.8 Hz, IH), 7.04 (dd, 7= 7.8,1.5 Hz, IH), 6.94 (m, IH), 2.30 (s, 3H), 2.29 (s, 3H).
Example 110: 3'-IN'-[l-(3.4-Dimethvl-phenvl)-6-ethvl-2-oxo-l .2-dihvdro-indol-3-ylidene]-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 210
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (300MHz, DMSO) 8 13.04 (s, IH), 12.99 (s, IH), 9.23 (s, IH), 8.12 (t, 7= 1.6 Hz, IH), 7.94 (ddd, 7= 7.6,1.6, 1.2 Hz, IH), 7.79 (ddd, 7= 7.6, 1.6,1.2 Hz, IH), 7.70 (dd, 7= 7.8,1.6 Hz, IH), 7.63 (d, 7= 7.5 Hz, IH), 7.59 (t, 7= 7.6 Hz, IH), 7.36 (d, 7= 8.0 Hz, IH), 7.29 (d, 7= 2.0 Hz, IH), 7.22 (dd, 7= 8.0, 2.0 Hz, IH), 7.10 (t, 7= 7.8 Hz, IH), 7.04 (m, IH), 6.98 (dd, 7= 7.8, 1.6 Hz, IH), 6.67 (m, IH), 2.61 (q, 7= 7.6 Hz, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 1.14 (t, 7= 7.6 Hz, 3H).

Example 111: 3'-IN'-ri-(3.4-Dimethvl-phenvl)-6-methoxv-2-oxo-1.2-dihvdro-indol-3-yIidenel-hvdrazmol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 211)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (300MHz, DMSO) 8 12.85 (s, IH), 9.16 (s, IH), 8.09 (t, J= 1.7 Hz, IH), 7.91 (ddd,/ = 7.6, 1.7, 1.2 Hz, IH), 7.76 (ddd, J = 7.6,1.7,1.2 Hz, IH), 7.66 (dd, .7= 7.9, 1.6 Hz, IH), 7.62 (d, J= 8.4 Hz, IH), 7.57 (t, J = 7.6 Hz, IH), 7.33 (d, J= 8.0 Hz, IH), 7.28 (d, J= 2.1 Hz, IH), 7.21 (dd, /= 8.0, 2.1 Hz, IH), 7.07 (t, J= 7.9 Hz, IH), 6.93 (dd, /= 7.9, 1.6 Hz, IH), 6.74 (dd, J= 8.4,2.2 Hz, IH), 6.33 (d, J = 2.2 Hz, IH), 3.73 (s, 3H), 2.29 (s, 3H), 2.28 (s, 3H).
Example 112: 3'-IN'-f5-Chloro-l-f3.4-dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vh'dene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 212)
(Figure Removed)

This compound was prepared as described in Scheme n. JH NMR (300MHz, DMSO) 5 13.25 (s, IH), 13.01 (s, IH), 9.49 (s, IH), 8.10 (t, /= 1.7 Hz, IH), 8.01 (s, IH), 7.93 (ddd,.7=7.7,1.7,1.1 Hz, IH), 7.83 (dd,.7=7.8,1.9 Hz, IH), 7.77 (ddd,.7 = 7.7, 1.7, 1.1 Hz, IH), 7.58 (t, J= 7.7 Hz, IH), 7.36 (d, 8.0 Hz, IH), 7.31 (d, 2.0 Hz, IH), 7.25 (dd, J= 8.0, 2.0 Hz, IH), 7.12 (t, J= 7.8 Hz, IH), 7.07 (dd, /= 7.8,1.9 Hz, IH), 7.02 (s, IH).

Example 113: 3'- IN'41-(3.44)imethvl-phenvlV6 J-dimethvl-2-oxo-l .2-dihvdro-indol-3-vlidenel-hvdrazinol-2'-hydroxv-biphenvl-3-carboxvlic acid (Compound 213)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (300MHz, DMSO) 5 13.03 (s, IH), 12.94 (s, IH), 9.17 (s, IH), 8.10 (t, J= 1.5 Hz, IH), 7.93 (d, J = 7.7 Hz, IH), 7.77 (d, J= 7.7 Hz, IH), 7.69 (dd, J= 7.8, 1.2 Hz, IH), 7.58 (t, J = 7.7 Hz, IH), 7.48 (d, J = 7.5 Hz, IH), 7.30 (d, J= 7.9 Hz, IH), 7.20 (d, J = 1.8 Hz, IH), 7.14 (dd, /= 7.9,1.8 Hz, IH), 7.09 (t, J= 7.8 Hz, IH), 7.02 (d, J = 7.8 Hz, IH), 6.96 (d,J= 7.5 Hz, IH), 2.31 (s, 3H), 2.28 (s, 3H), 2.23 (s,3H), 1.62 (s,3H).
Example 114: 2-(3'- IN'-[l-(3.4-Dimethvl-phenvl)-_2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biphenvl-4-vn-2-methvl-propionic acid (Compound 214)
(Figure Removed)
This compound was prepared as in Scheme H 'H NMR (300MHz, DMSO) 8 13.23 (s, IH), 12.39 (s, IH), 9.35 (s, IH), 7.92 (d, J= 7.9 Hz, IH), 7.74 (dd, J= 7.8, 1.7 Hz, IH), 7.55 (d, J = 8.5 Hz, 2H), 7.53 (m, IH), 7.45 (d, /= 8.5 Hz, 2H), 7.39 (d, J = 8.0 Hz, IH), 7.33 (d, J = 2.2 Hz, IH), 7.27 (dd, J= 8.0, 2.2 Hz, IH), 7.11 (t, J= 7.8 Hz, IH), 7.03 (dd, J = 7.8, 1.7 Hz, IH), 6.96 (m, IH), 2.32 (s, 3H), 2.31 (s, 3H), 1.52 (s, 6H).

Example 115: (-)-2-(3'-IN'-[l-f3.4-Dimethvl-phenyl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino-2'-hvdroxv-biphenvl-4-vn-propionic acid (Compound 215) and (+)-2-(3'-{N'-[l-(3.4-Dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-ylidene1-hvdrazinol-2'-hvdroxv-biphenvl-4-vl')-propioiiic acid (Compound 215a)
(Figure Removed)
These compounds were prepared as described in Scheme II. 'H NMR (300MHz, DMSO) 8 13.23 (s, IH), 12.36 (s, IH), 9.34 (s, IH), 7.92 (d, /= 7.9 Hz, IH), 7.74 (dd, J = 7.8,1.6 Hz, IH), 7.53 (d, J = 8.4 Hz, 2H), 7.53 (m, IH), 7.39 (d, J = 8.4 Hz, 2H), 7.38 (d, J= 8.2 Hz, IH), 7.33 (d, /= 2.0 Hz, IH), 7.27 (dd, J = 8.2, 2.0 Hz, IH), 7.11 (t, J= 7.8 Hz, IH), 7.02 (dd, /= 7.8, 1.6 Hz, IH), 6.96 (m, IH), 3.73 (q, J = 7.0 Hz, IH), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J= 7.0 Hz, 3H).
Example 116: (±)-(3'-{N'-[l-(vlidene]-hvdrazinol -2'-hvdroxv-5'-methvl-biphenvl-4-vlVpropionic acid (Compound 216)
(Figure Removed)


This compound was prepared as in Scheme D. !H NMR (300MHz, DMSO) 8 13.21 (s, IH), 12.34 (s, IH), 9.07 (s, IH), 7.94 (d, J= 8.0 Hz, IH), 7.57 (d, J = 1.6 Hz, IH), 7.53 (d, J= 8.0 Hz, IH), 7.52 (d, J= 8.3 Hz, 2H), 7.38 (d, J= 8.0 Hz, IH), 7.37 (d, J= 8.3 Hz, 2H), 7.33

(d, J = 2.0 Hz, IH), 7.27 (dd, /= 8.0,2.0 Hz, IH), 6.96 (m, IH), 6.85 (d, J= 1.6 Hz, IH), 3.73 (q, J = 7.0 Hz, IH), 2.35 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J= 7.0 Hz, 3H).
Example 117: (+)-2-(3'-IN'-[l-f3.4-Diinethvl-pheiivn-2-ox:o-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-5'-fluoro-2'-hvdroxv-biphenvl-4-vlVpropionic acid (Compound 217)

(Figure Removed)
This compound was prepared as in Sclieme H 'H NMR (300MHz, DMSO) 5 13.13 (s, IH), 12.37 (s, IH), 9.26 (s, IH), 7.99 (d, J= 7.8 Hz, IH), 7.57 (d, J = 8.4 Hz, 2H), 7.55 (m, IH), 7.53 (dd, J= 9.7, 3.1 Hz, IH), 7.40 (d, J= 8.4 Hz, 2H), 7.39 (m, IH), 7.33 (d, J= 2.0 Hz, IH), 7.27 (dd, J= 7.9, 2.0 Hz, IH), 6.96 (m, IH), 6.86 (dd, .A= 9.4, 3.1 Hz, IH), 3.74 (q, J= 7.1 Hz, IH), 2.32 (s, 3H), 2.31 (s, 3H) 1.40 (d, J= 7.1 Hz, 3H).
Example 118: 5-(4-(N'-ri-(3.4-Dimethvl-phenvl)-5.7-diflu.oro-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino-3-hvdroxv-ben2vlidene)-thiazolidine-2.4-dione (Compound 218)
(Figure Removed)
This compound was prepared as in Scheme V. *H NMR (300MHz, DMSO) 5 13.03 (s, IH), 12.56 (s, IH), 10.86 (s, IH), 7.80 (d,y= 8.4 Hz, IH), 7.68 (s, IH), 7.46 (dd, J = 7.6, 2.3 Hz, IH), 7.30-7.18 (m, 5H), 7.14 (d, J= 1.6 Hz, IH), 2.30 (s, 3H), 2.28 (s, 3H).

Example 119: 5-(4- N-[-(4-Ethvl-phenvlV5.7-difluoro-2-oxo-1.2-dihvdro-indol-3-vlidene1-hdrazinol-3-hvdrox-benzylidene)-thiazolidine-2.4-dione (Compound 219")

(Figure Removed)
This compound was prepared as in Scheme V. 'H NMR (500MHz, DMSO) 5 13.03 (s, IH), 12.56 (s, IH), 10.87 (s, IH), 7.80 (d, J= 8.3 Hz, IH), 7.68 (s, IH), 7.47 (dd, J = 7.5, 1.8 Hz, IH), 7.41 (d, J= 8.2 Hz, 2H), 7.36 (d, J= 8.2 Hz, 2H), 7.27-7.21 (m, 2H), 7.14 (s, IH), 2.70 (q, J= 7.6 Hz, 2H), 1.24 (t, J= 1.6 Hz, 3H).
Example 120: 5-f4- (N'-r5.7-Difluoro-2-oxo-l -(propvl-phenvlH .2-dihvdro-indol-3-vlidene1-hydrazinol-3-hvdroxy-benzylidenethiazolidine-2.4-dione (Compound 220)
(Figure Removed)
This compound was prepared as in Scheme V. JH NMR (500MHz, DMSO) 8 13.03 (s, IH), 12.56 (s, IH), 10.87 (s, IH), 7.80 (d, / = 8.3 Hz, IH), 7.69 (s, IH), 7.46 (dd, J = 7.7, 2.3 Hz, IH), 7.40 (d, /= 8.2 Hz, 2H), 7.34 (d, J= 8.2 Hz, 2H), 7.26-7.20 (m, 2H), 7.14 (d, /= 1.6 Hz, IH), 2.64 (t, J = 7.4 Hz, 2H), 1.65 (q, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H).

Example 121: 5 -( 3 -Hvdroxv-4- IN'-[ 1 -(44sopropyl-phenvl)-2-oxo-6-trifluoromethyl-l .2-dihvdro-indl-3-lidene-hvdrazino}-benzvlidene')-thiazolidine-2.4-dione (Compound 221)

(Figure Removed)
This compound was prepared as in Scheme V. *H NMR (500MHz, DMSO) S 13.13 (s, IH), 12.57 (s, IH), 10.89 (s, IH), 7.92 (d, 7= 7.8 Hz, IH), 7.81 (d, J = 8.4 Hz, IH), 7.69 (s, IH), 7.55 (d, J = 7.8 Hz, IH), 7.51 (d, J= 8.6 Hz, 2H), 7.48 (d, 7 = 8.6 Hz, 2H), 7.25 (dd, 7 = 8.4, 1.6 Hz, IH), 7.16 (d, 7= 1.6 Hz, IH), 6.99 (s, IH), 3.02 (sept, 7= 6.9 Hz, IH), 1.28 (d, 7= 6.9 Hz,6H).
Example 122: 5-f3-Hvdroxv-4-IN'-[l-f4-isopropyl-phenvl)-2-oxo-5.7-difluoro-1.2-dihvdro-indol-S-ylidenel-hydrazino-benzvlidenel-thiazolidine-5-dione (Comound 222)

(Figure Removed)


This compound was prepared as in Scheme V. 1H NMR (500MHz, DMSO) 8 13.05 (s, IH), 12.56 (s, IH), 10.87 (s, IH), 7.81 (d, 7= 8.4 Hz, IH), 7.69 (s, IH), 7.48 (dd, 7 = 7.7, 2.1 Hz, IH), 7.42 (d, 7= 8.4 Hz, 2H), 7.39 (d, 7= 8.4 Hz, 2H), 7.27-7.21 (m, 2H), 7.15 (d, 7= 1.6 Hz, IH), 2.99 (sept, 7= 7.0 Hz, IH), 1.26 (d, 7= 7.0 Hz, 6H).

Example 123:
vlidene]-hvdrazino-5'-fluoro-2'-hvdroxv-biphenvl-3-carboxylic acid (Compound 223)

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 5 13.14 (s, IH), 13.08 (s, IH), 9.35 (s, IH), 8.15 (m, IH), 8.00 (d, J = 7.8 Hz, IH), 7.96 (dd, J= 7.7,1.2 Hz, IH), 7.82 (m, IH), 7.61 (t, 7= 7.7 Hz, IH), 7.57 (dd, 7=9.2, 3.0 Hz, IH), 7.55 (d, J= 7.7 Hz, IH), 7.39 (d, 7 = 8.1 Hz, IH), 7.33 (d, 7 = 1.5 Hz, IH), 7.27 (dd, 7 = 8.1, 1.5 Hz, IH), 6.95 (s, IH), 6.92 (dd, 7= 9.2,3.0 Hz, IH), 2.32 Cs, 3H), 2.31 (s, 3H).
Example 124: S'-Chloro-S'-IN'-fl-D-dimethvl-plieiivn-oxo-e-trifluoromethvl-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-caTboxvlic acid (Compound 224^
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 5 13.12 (s, IH), 13.09 (s, IH), 9.68 (s, IH), 8.12 (t, 7 = 1.7 Hz, IH), 8.02 (d, 7 = 7.8 Hz, IH), 7.97 (ddd, 7= 7.7, 1.7, 1.1 Hz, IH), 7.81 (ddd, J= 7.7, 1.7, 1.1 Hz, IH), 7.76 (d, J- 2.6 Hz, IH), 7.61 (t, 7 = 7.7 Hz, IH), 7.54 (d, 7= 7.8 Hz, 1H)9 7.39 (d, J - 8.0 Hz, IH), 7.33 (d, 7= 2.0 Hz, IH), 7.27 (dd, 7= 8.0,2.0 Hz, IH), 7.08 (d, 7= 2.6 Hz, IH), 6.95 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H).

Example 125: 3'-IN'-ri-(3.4-Dimethvl-phenvl)-2-oxo-6-tnnuoromethyl-1.2-dihydro-indol-3-vlidenel-hydrazino\-2'-hvdroxv-5'-methvl-biphenvl-3-carboxvlic acid. (Compound 225)

(Figure Removed)
This compound was prepared as described in Scheme II. *H NMR (500MHz, DMSO) 5 13.22 (s, IH), 13.04 (s, IH), 9.16 (s, IH), 8.11 (t, /= 1.6 Hz, IH), 7.94 (ddd,J= 7.7, 1.6, 1.2 Hz, IH), 7.94 (d, J = 7.8 Hz, IH), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, IH), 7.61 (d, J= 1.9 Hz, IH), 7.59 (t, J = 7.7 Hz, IH), 7.53 (d, J= 7.8 Hz, IH), 7.38 (d, J= 8.0 Hz, IH), 7.33 (d, J = 1.9 Hz, IH), 7.27 (dd, J= 8.0,1.9 Hz, IH), 6.96 (s, IH), 6.89 (d, J= 1.9 Hz, IH), 2.37 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H).
Example 126: 2'-Hvdroxv-3'-IN'-[2-oxo-6-lrifluoroniethvl-l-f4-trifluoromethvl-phenvn-1.2-dlhvdro-indol-3-vlidene1-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 226)
(Figure Removed)

This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO) 8 13.20 (s, IH), 13.06 (s, IH), 9.48 (s, IH), 8.12 (m, IH), 8.01 (d, J = 8.4 Hz, 2H), 7.98-7.94 (m, 2H), 7.86 (d, J= 8.4 Hz, 2H), 7.81-7.78 (m, 2H), 7.61 (t, / = 7.7 Hz, IH), 7.59 (d, J = 7.5 Hz, IH), 7.20 (s, IH), 7.15 (t, J= 7.8 Hz, IH), 7.08 (dd, J = 7.8,1.2 Hz, IH).

Example 127: 3'-(N'-ri-(4-Ethvl-3-meihvl-tihenvl')-2-oxo-6-trifluoromethvl-L2-dihvdro-indol-3-ylidene]-hvdrazinol-2'-hydroxv-biphenvl-3-carboxvlic acid (Compound 227)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO) 8 13.24 (s, IH), 13.05 (s, IH), 9.43 (s, IH), 8.12 (m, IH), 7.96-7.91 (m, 2H), 7.81-7.77 (m, 2H), 7.61 (t, J= 7.7 Hz, IH), 7.54 (d, J= 8.0 Hz, IH), 7.40 (d, J= 7.9 Hzs IH), 7.34-7.30 (m, 2H), 7.14 (t, J= 7.8 Hz, IH), 7.06 (d, J= 7.8 Hz, IH), 6.97 (s, IH), 2.69 (q, J= 7.5 Hz, 2H), 2.35 (s, 3H))1.23(t,/=7.5Hz,3H).
Example 128: 3'-{N-[l -Chloro-S-trifluorometh-vl-phenvD-oxo-e-trifluoromethvl-l-dihvdro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-bipIienvl-3-carboxvlic acid (Compound 228)

(Figure Removed)
This compound was prepared as described in. Scheme n. ]H NMR (500MHz, DMSO) 8 13.16 (s, IH), 13.05 (s, IH), 9.48 (s, 1EQ, 8.14 (d, J- 2.1 Hz, IH), 8.12 (t, J= 1.5 Hz, IH), 8.01-7.93 (m, 4H), 7.81-7.78 (m, 2H), 7.61 (t, J= 7.7 Hz, IH), 7.58 (d, J= 8.0 Hz, IH), 7.23 (s, IH), 7.15 (t, J = 1.1 Hz, IH), 7.08 (dd, J= 7.7, 1.3 Hz, IH).

Example 129: 3'-IN'-ri-(3.5-Dimethvl-phenvn-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-vlidene]-hvdrazinol-5'-fluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 229)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO) 8 13.14 (s, IH), 13.09 (s, IH), 9.35 (s, IH), 8.16 (t, 7= 1.6 Hz, IH), 8.00 (d, J= 7.9 Hz, IH), 7.97 (ddd,/= 7.8, 1.6, 1.0 Hz, IH), 7.82 (ddd,y= 7.8,1.6, 1.0 Hz, IH), 7.62 (t, 7= 7.8 Hz, IH), 7.57 (dd, J = 9.5, 3.1 Hz, IH), 7.56 (m, IH), 7.17 (s, IH), 7.16 (s, 2H), 6.98 (s, IH), 6.92 (dd, J= 9.3,3.1 Hz, IH), 2.37 (s, 6H).
Example 130: 3'-W-ri-(3.4-Dimethvl-phenvn-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene]-hvdrazino)-4.5'-difluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 230)
(Figure Removed)

This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 6 13.37 (s, IH), 13.11 (s, IH), 9.35 (s, IH), 8.04 (dd, /= 1.5, 7.0 Hz, IH), 7.98 (d, J= 7.5 Hz, IH), 7.82-7.79 (m, IH), 7.56-7.53 (m, 2H), 7.41 (t, /= 10.5 Hz, IH), 7.37 (d, J= 8.5 Hz, IH), 7.31 (s, IH), 7.26 (d, J= 8 Hz, IH), 6.94 (s, IH), 6.91 (dd, /= 2.5, 9.5 Hz, IH), 2.29 (s, 6H).

Example 131: 3'-(N'-[ 1 -(3.5-Dimethvl-phenv)-2-oxo-6-trifluoromethvl-l .2-dihvdro-indol-3-vlidene1-hvdrazino-4.5'-difluoro-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 231)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 8 13.37 (s, IH), 13.11 (s, IH), 9.35 (s, IH), 8.04 (dd,7 = 1.5, 7.0 Hz, IH), 7.98 (d,J= 7.5 Hz, IH), 7.82-7.79 (m, IH), 7.56-7.53 (m, 2H), 7.41 (t,7= 10.5 Hz, IH), 7.16 (s, IH), 7.15 (s, IH), 6.96 (s, IH), 6.91 (dd, J= 2.5,9.5 Hz, IH), 2.35 (s, 6H).
Example 132: 4.5'-Difluoro-2'-hvdroxv-3'-(N'-|2-oxo-6-trifluoromethvl-l-(4-trifluoromethvl-phenvlV1.2-dihvdro-indol-3-vlidene]-hvdrazinol-biphenvl-3-carboxvlic acid (Compound 232^
(Figure Removed)
This compound was prepared as described in Scheme EL H NMRXH NMR (500MHz, DMSO) 8 13.37 (s, IH), 13.07 (s, IH), 9.39 (s, IH), 8.04 (dd, 7= 1.5, 7.0 Hz, IH), 7.97 (d, J= 9.0 Hz, IH), 7.82-7.79 (m, IH), 7.59-7.56 (m, 2H), 7.42 (t, /= 9.5 Hz, IH), 7.18 (s, IH), 6.92 (dd, 7=3.0,9.5 Hz, IH).

Example 133: 3'-{N'-[l-(4-Fluoro-3.5-dimethvl-phenvl-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-vIidene1-hvdrazino)-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 233)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 5 13.20 (s, IH), 13.04 (s, IH), 9.42 (s, IH), 8.10 (s, IH), 7.94-7.89 (m, 2H), 7.79-7.75 (m, 2H), 7.59 (t, J = 13 Hz, IH), 7.52 (d, J = 13.5 Hz, IH), 7.30 (d, J= 10.5 Hz, IH), 7.12 (t, J= 13 Hz, IH), 7.04 (dd, J = 2.0,12.5 Hz, IH), 6.98 (s, IH), 2.29 (s, 6H).
Example 134: 2'-Hvdroxv-3'- (N'-[ 1 -(4-methoxv-phenvl)-2-oxo-6-trifluoromethyl-1.2-dihydro-indol-3-vlidene1-
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500MHz,
8 13.21 (s, IH), 13.04 (s, IH), 9.41 (s, IH), 8.10 (s, IH), 7.92 (dd, J = 7.5, 12 Hz, 2H),
r= 7.5 Hz, 2H), 7.59 (t, J= 7.5 Hz, IH), 7.52 (d, J= 7.5 Hz, IH), 7.47 (d, J= 8.5 Hz, 2H),
= 8.5 Hz, 2H), 7.12 (d, J= 8.0 Hz, IH), 7.05 (dd,/= 1.0, 8.0 Hz, IH), 6.92 (s, IH), 3.84

Example 135: 3'-IN'-[l-(4-Fluoro-phenyn-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 235)
(Figure Removed)

This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) 8 13.19 (s, IH), 13.04 (s, IH), 9.43 (s, IH), 8.10 (s, IH), 7.93 (t, / = 6.0 Hz, 2H), 7.78 (t, J = 6.0 Hz, 2H), 7.65-7.62 (m, 2H), 7.59 (t, 7= 7.0 Hz, IH), 7.54 (d, J= 8.5 Hz, IH), 7.46 (d, J= 8.5 Hz, 2H), 7.13 (t, J= 8.0 Hz, IH), 7.05 (dd, /= 1.5, 8.0 Hz, IH), 6.99 (s, IH).
Example 136: 3'-IN'-[l-(3.5-Dimethoxv-phenvn-2-oxo-6-trifluoromethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-biDhenvl-3-carboxvlic acid (Compound 236)

(Figure Removed)
This compound was prepared as described in Scheme E. 'H NMR (500MHz, DMSO) 8 13.21 (s, IH), 13.04 (s, IH), 9.44 (s, IH), 8.11 (s, IH), 7.92 (dd, /= 8.0, 10.5 Hz, 2H), 7.78 (t, J = 7.5 Hz, 2H), 7.59 (t,J = 7.5 Hz, IH), 7.53 (d, /- 8.0 Hz, IH), 7.13 (t, J= 8.0 Hz, IH), 7.06-7.04 (m, 2H), 6.73 (s, 2H), 6.66 (s, IH), 3.79 (s, 6H).

Example 137: 3'-IN'-ri-f3.4-Dimethoxv-phenvH-2-oxo-6-trifluoromethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 237)

(Figure Removed)
This compound was prepared as described in Scheme EL 1H NMR (500MHz, DMSO) 8 13.23 (s, IH), 13.04 (s, IH), 9.42 (s, IH), 8.11 (s, IH), 7.92 (dd, J = 7.5, 14.0 Hz, 2H), 7.78 (t, J= 1.5 Hz, 2H), 7.59 (t, /== 7.5 Hz, IH), 7.52 (d, /= 8.0 Hz, IH), 7.17-7.04 (m, 5H), 6.96 (s, IH), 3.84 (s, 3H), 3.76 (s, 3H).
Example 138: 3'- IN'-[ 1 -(3.5 -Difluoro-phenvl V2-oxo-6-teifluoromethyl-1.2-dihvdro-indol-3 -vlidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 238)
(Figure Removed)

This compound was prepared as described in Scheme EL *H NMR (500MHz, DMSO) 5 13.16 (s, IH), 13.04 (s, IH), 9.48 (s, IH), 8.11 (s, IH), 7.94 (d, J= 7.5Hz, 2H), 7.80-7.77 (m, 2H), 7.60 (t, J= 7.5, Hz, IH), 7.57 (d, J= 8.0 Hz, IH), 7.46-7.44 (m, 3H), 7.22 (s, IH), 7.13 (t, /= 7.5 Hz, IH), 7.06 (d, J= 7.5 Hz, IH).

Example 139: 5'-Fluoro-3'-(N'-[l-('4-fluoro-3.5-dimethvl-phenyl')-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 239")
(Figure Removed)
This compound was prepared as described in Scheme ft 'H NMR (SOOMHz, DMSO) 8 13.11 (s, IH), 13.07 (s, IH), 9.34 (s, IH), 8.14 (s, IH), 7.97 (dd, /= 7.5, 16.0 Hz, 2H), 7.81 (d, J= 7.5 Hz, IH), 7.60 (t, /= 7.5, Hz, IH), 7.57-7.54 (m, 2H), 7.31 (d, J= 6.0 Hz, 2H), 6.98 (s, IH), 6.91 (dd, J= 2.5, 9.5 Hz, IH), 2.29 (s, 6H).
Example 140: 4.5'-Difluoro-3'-(N'-[l-(4-fluoro-3.5-dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 2401
(Figure Removed)
This compound was prepared as described in Scheme It. 'H NMR (SOOMHz, DMSO) 5 13.37 (s, IH), 13.10 (s, IH), 9.35 (s, IH), 8.04 (dd, J= 2.0, 7.0 Hz, IH), 7.98 (da J= 7.5 Hz, IH), 7.82-7.79 (m, IH), 7.57-7.54 (m, 2H), 7.42 (t, J= 9.0 Hz, IH), 7.30 (d, J= 6.5 Hz, 2H), 6.98 (s, IH), 6.91 (dd, J- 2.5, 9.5 Hz, IH), 2.29 (s, 6H).

Example 141: 2'-Hvdroxv-3'-fN'-[l-/4-methoxy-3.5-dimethvl-phenvn-2-oxo-6-trifluoromethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazinoy-biphenvl-3-carboxvlic acid (Compound 241)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, DMSO) S 13.21 (s, IH), 13.03 (s, IH), 9.40 (s, IH), 8.10 (s, IH), 7.91 (dd,J= 8.0, 15.0 Hz, 2H), 7.77 (t, J= 7.5 Hz, 2H), 7.59 (t, J= 8.0 Hz, IH), 7.52 (d, J - 7.5 Hz, IH), 7.21 (s, 2H), 7.12 (t, J= 8.0 Hz, IH), 7.04 (dd, J= 1.5, 7.5 Hz, IH), 6.96 (s, IH), 3.73 (s, 3H), 2.29 (s, 6H).
Example 142: 2'-Hvdroxv-3'-(N'-[l-(4-hvdroxy-3.5-dimethyl-phenyl')-2-oxo-6-trifluoromethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazin.o}-biphenvl-3-carboxvlic acid (Compound 242)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO) 8 13.22 (s, IH), 13.03 (s, IH), 9.39 (s, IH), 8.69 (s, IH) , 8.10 (s, IH) , 7.93 (d, J= 8.0 Hz, IH), 7.88 (d, J= S.OHz, IH), 7.78-7.75 (m, 2H), 7.58 (t, J= 8.0 Hz, IH), 7.50 (d, J= 8.5 Hz, IH), 7.11 (t, J= 8.0 Hz, IH), 7.06 (s, 2H), 7.03 (dd,J= 1.5,7.5 Hz, IH), 6.89 (s, IH), 2.21 (s, 6H).

Example 143: S'-IN'-ri-Cvclohexvl-phenvn-oxo-l-dihvdro-indol-S-ylidenel-hvdrazinc 2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 243)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSCMs) 5 13.06 (s, IH), 9.27 (s, IH), 8.11 (s, IH), 7.94 (d, .7=7.8 Hz, IH), 7.79 (d, .7=7.8 Hz, IH), 7.73 (m, 2H), 7.60 (t, .7=7.8 Hz, IH), 7.44 (s, 4H), 7.29 (t, .7=7.6 Hz, IH), 7.19 (t, .7=7.6 Hz, IH), 7.11 (t, 7=7.8 Hz, IH), 7.00 (d, 7=7.6 Hz, IH), 6.88 (d, 7=7.6 Hz, IH), 2.61 (m, IH), 1.85 (m, 4H), 1.72 (m, IH), 1.44 (m, 4H), 1.26 (m, IH).
Example 144: 2'-Hydroxy-3'-[N'-(2-oxo-l-pyridin-2-vl-1.2-dihvdro-indol-3-ylidene)-hYdrazino]-biphenvl-3-carboxylic acid (Compound 244")
(Figure Removed)
This compound was prepared as described in Scheme EL *H NMR (500 MHz, 5 13.08 (s, IH), 9.34 (s, IH), 8.66 (ddd, 7=4.9,1.9, 0.9 Hz, IH), 8.13 (t, 7=1.6 Hz, IH), 8.07 (ddd, 7=7.6, 8.0,1.9 Hz, IH), 7.95 (ddd, 7=7.7,1.6, 1.2 Hz, IH), 7.89 (dt, 7=8.0, 1.0 Hz, IH), 7.81 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.77-7.74 (m, 2H), 7.67 (d, 7=7.8 Hz, IH), 7.61 (t, 7=7.7 Hz, IH), 7.47 (ddd, 7=7.6, 4.9, 1.0 Hz, IH), 7.34 (td, 7=7.8, 1.3 Hz, IH), 7.25 (td, 7=7.8, 0.9 Hz, IH), 7.13 (t, 7=7.8 Hz, IH), 7.02 (dd, 7=7.8,1.6 Hz, IH).

Example 145: 2'-Hvdroxy-3'-[N'-(2-oxo-l-pvridin-3-vl-1.2-dihvdro-indol-3-ylideneVhvdrazino1-biphenyl-3-carboxvlic acid (Compound 245)
This compound was prepared as described in Scheme II. *H NMR (300 MHz, 6 13.02 (s, (Figure Removed)
IH), 9.33 (s, IH), 8.81 (s, IH), 8.69 (s, IH), 8.12 (t, y=1.6 Hz, IH), 8.05 (ddd, .7=8.2, 2.0, 1.6 Hz, IH), 7.94 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.82-7.73 Cm, 3H), 7.67 (m, IH), 7.60 (t, 7=7.7 Hz, IH), 7.32 (td, 7=7.6,1.4 Hz, IH), 7.23 (td, 7=7.6,1.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.02 (dd, 7=7.8,1.7 Hz, IH), 6.94 (d, 7=7.8 Hz, IH).
Example 146: 3'-{N'-[l-(4-Ethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihvc3ro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 246)
(Figure Removed)

This compound was prepared as described in Scheme I. *H NMR (300 MHz, DMSO-40 8 13.21 (s, IH), 13.04 (s, IH), 9.42 (s, IH), 8.10 (s, IH), 7.96-7.88 (m, 2H), 7.80-7.74 (m, 2H), 7.58 (t, 7=7.7 Hz, IH), 7.52 (d, 7=7.9 Hz, IH), 7.46 (s, 4H), 7.12
Example 147: 3'-IN'-[ 1 -(4-Ethvl-phenvD-4-fluoro-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene]-hvdrazino}-2'-hydroxv-biphenvl-3-carboxvlic acid (Compound 2471
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 8 13.36 (s, IH), 13.05 (s, IH), 9.50 (s, IH), 8.12 (t, .7=1.6 Hz, IH), 7.95 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.80 (ddd, .7=7.7, 1.6,1.2 Hz, IH), 7.67 (dd, .7=7.8, 1.6 Hz, IH), 7.60 (t, .7=7.7 Hz, IH), 7.51 (d, .7=9.5 Hz, IH), 7.47 (s, 4H), 7.15 (t, .7=7.8 Hz, IH), 7.08 (dd, 7=7.8,1.6 Hz, IH), 6.83 (s, IH), 2.72 (q, 7=7.6 Hz, 2H), 1.26 (t, 7=7.6 Hz, 3H).
Example 148: 3-[f'-Carboxv-2-hydroxy-biphenyl-3-ylVhvdrazono]-!-(3.5 -dimethvl-p!henvlV2-oxo-2.3-dihvdro-l-H-indole-5-carboxvlic acid methyl ester (Compound 248")
(Figure Removed)
This compound was prepared as described in Scheme IT. *H NMR. (300 MHz, DMSO-40 8 13.07 (s, IH), 13.05 (s, IH), 9.37 (s, IH), 8.25 (s, IH), 8.12 (s, IH), 7.97-7.89 (m, 2H), 7.83-7.77 (m, 2H), 7.60 (t, 7=7.8 Hz, IH), 7.46 (s, 4H), 7.13 (t, .7=7.8 Hz, IH), 7.O4 (d, .7=7.8 Hz, IH), 6.97 (d, .7=8.6 Hz, IH), 3.89 (s, 3H), 2.72 (q, 7=7.5 Hz, 2H), 1.25 (t, 7=7.5 Hz, 3H)
.
Example 149: 3'-{N'-[l-f3-Chloro-4-methvl-phenvl)-2-oxo-6-trifluoromethyl-l.2-dihvdro-indol-3-vlidene]-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 249^
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-d6) 5 13.19 (s, IH), 13.05 (s, 1H)3 9.46 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.95 (ddd, 7=7.6, 1.7,1.2 Hz, 1H),7.93 (d, 7=7.9 Hz, IH), 7.80 (ddd, 7=7.6, 1.7, 1.2 Hz, IH), 7.78 (dd, 7=7.8,1.6 Hz, IH), 7.70 (d, 7=2.1 Hz, IH), 7.61 (t, 7=7.6 Hz, IH), 7.61 (d, 7=8.2 Hz, IH), 7.56 (dq, 7=7.9 , 0.7 Hz, IH), 7.49 (dd, 7=8.2, 2.1 Hz, IH), 7.14 (t, 7=7.8 Hz, IH), 7.07 (dd, 7=7.8,1.6 Hz, IH), 7.04 (m, IH), 2.44 (s, 3H).
Example 150: 5-(4-fN'-[l-f3.5-Dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-vlidene]-hvdrazino)-3-hvdroxy-benzvlideneVthiazolidine-2.4-dione (Compound 250")
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, 5 13.12 (s, IH), 12.57 (s, IH), 10.88 (s, IH), 7.91 (d, 7=7.9 Hz, IH), 7.80 (d, 7=8.4 Hz, IH), 7.68 (s, IH), 7.54 (dq, 7=7.9, 0.8 Hz, IH), 7.24 (dd, 7=8.4,1.8 Hz, IH), 7.18 (s, IH), 7.17-7.15 (m, 3 H), 6.97 (m, IH), 2.37 (s, 6H).

Example 151: 2'-Hvdroxv-3'-rN'-(2-oxo-l-r4-(4.4.4-trifluoro-butvn-phenvl]-1.2-dihydro-indol-3-vlidene}-hvdrazino)-birhenvl-3-carboxvlic acid (Compound 251)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMDR. (500 MHz, 6 13.02 (s, IH), 9.26 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 7.95 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.79 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.69 (dd, 7=7.8, 1.6 Hz, IH), 7.65 (dd, .7=7.6, 1.2 Hz, IH), 7.60 (t, .7=7.7 Hz, IH), 7.35 (td, 7=7.6,1.2 Hz, IH), 7.24 (d, .7=7.6 Hz, IH), 7.14 (td, 7=7.6, 0.8 Hz, IH), 7.10 (t, 7=7.8 Hz, IH), 6.98 (dd, 7=7.8,1.6 Hz, IH), 3.90 (t, 7=7.0 Hz, 2H), 2.39 (m, 2H), 1.88 (m, 2H).
Example 152: 3'- (N'-F 1 -(3.5-Dimethvl-phenvl)-4-fluoro-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene]-hydrazino}-2'-hvdi'oxv-biphenvl-3-carboxvlic acid (Compound 252)
(Figure Removed)
This compound was prepared as described in Scheme n. ]H NMDR. (500 MHz, DMSO-4) 8 13.37 (s, IH), 13.06 (s, IH), 9.49 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.95 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.80 (ddd, 7=7.7,1.7,1.2 Hz, IH), 7.67 (dd, 7=7.8,1.6 Hz, IH), 7.61 (t, 7=7.7 Hz,

IH), 7.50 (d, 7=9.5 Hz, IH), 7.18 (m, IH), 7.16 (m, 2H), 7.15 (t, 7=7.8 Hz, IH), 7.08 (dd, 7=7.8, 1.6 Hz, IH), 6.83 Cs, IH), 2.37 (s, 6H).
Example 153: 3'- IN'-[l-f4-tert-Butvl-phenvlV2-oxo-6-trifluoromethvl-1.2-dihvdro-indoI-3-vlidene1-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 253")
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dtf) 8 13.23 (s, IH), 13.05 (s, IH), 9.44 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.95 (ddd, 7=7.7, 1.7,1.1 Hz, IH), 7.93 (d, 7=7.8 Hz, IH), 7.80 (ddd,7=7.7, 1.7,1.1 Hz, IH), 7.78 (dd,7=7.8,1.6Hz, IH), 7.65 (d, 7=8.7 Hz, 2H), 7.61 (t, 7=7.7 Hz, IH), 7.55 (dq, 7=7.8, 0.7 Hz, IH), 7.50 (d, 7=8.7 Hz, 2H), 7.14 (t, 7=7.8 Hz, IH), 7.06 (dd, 7=7.8,1.6 Hz, IH), 7.01 (q, 7=0.8 Hz, IH), 1.36 (s, 9H).
Example 154: 3'- IN'-[l-f3.4-Dimethvl-phenvl)2-oxo-6-trifluoromethvl-1.2-dihvdro-mdol-3-vlidene1-hvdrazino-2'-hvdroxv-biphenvl-4-carboxvlic acid (Compound 254")
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500MHz, CD3OD) 5 8.09 (d, 7=8.2 Hz, 2H), 7.89 (d, 7=7.9 Hz, IH), 7.81 (dd, 7=7.9, 1.6 Hz, IH), 7.63 (d, 7=8.2 Hz, 2H), 7.47 (d, 7=7.9 Hz, IH), 7.38 (d, 7=8.0 Hz, IH), 7.26 (d, 7=1.8 Hz, IH), 7.19 (dd,

,7=8.0,1.8 Hz, IH), 7.10 (t, 7=7.9 Hz, IH), 7.04 (dd, .7=7.9, 1.6 Hz, IH), 6.99 (s, IH), 2.38 (s, 3H), 2.37 (s, 3H).
Example 155: 3'- IN'-[ 1 -(3.4-Dimethyl-phenylV2-oxo-6-bromo-l .2-dihvdro-indol-3-ylidene] -hvdrazmo}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 255)
(Figure Removed)
This compound was prepared as described in Scheme II H NMR (500MHz, DMSO-4,) 8 13.08 (s, IH), 13.04 (s, IH), 9.33 (s, IH), 8.12 (m, IH), 7.94 (d, .7=7.7 Hz, IH), 7.79 (m, IH), 7.74 (d, .7=7.7 Hz, IH), 7.67 (d, 7=8.0 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.37 (d, .7=8.0 Hz, IH), 7.37 (d, .7=8.0 Hz, IH), 7.31 (d, 7=1.8 Hz, IH), 7.24 (dd, 7=8.0, 1.8 Hz, IH), 7.12 (t, 7=7.9 Hz, IH), 7.03 (m, IH), 6.91 (m, IH), 2.32 (s, 3H), 2.31 (s, 3H).
Example 156: 3'{N'-[l-G.4-Pimethvl-phenvlV2-oxo-6-lTifluorometfavl-1.2Klihvdro-indol-3-vlidene1-hvdrazino}-3-fluoro-2'-hvdroxv-biphenvl-4-carboxvlic acid (Compound 256)

(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO-4) 8 13.27 (s, IH), 13.22 (s, IH), 9.59 (s, IH), 7.97-7.91 (m, 2H), 7.81 (dd, 7=7.7, 1.5 Hz, IH), 7.54 (d, 7=7.6 Hz, IH), 7.51-7.47 (m, 2H), 7.39 (d, 7=8.0 Hz, IH), 7.33 (d, 7=1.8 Hz, IH),

7.27 (dd, 7=8.0, 1.8 Hz, IH), 7.15 (t, 7=7.7 Hz, IH), 7.10 (dd, 7=7.7,1.5 Hz, IH), 6.96 (s, IH), 2.32 (s,3H),2.31(s,3H).
Example 157: S'-IN'-ri-O.S-Bis-trifluoromethvl-phenvDoxo-e-trifluoromethvl-l-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 257)

(Figure Removed)
This compound was prepared as described in Scheme II. :H NMR (300MHz, CD3OD) 5 8.24 (s, 2H), 8.11 (s, 2H), 7.99-7.92 (m, 2H), 7.81 (m, IH), 7.65 (m, IH), 7.56-7.45 (m, 2H), 7.18 (s, IH), 7.11-7.02 (m, 2H).
Example 158: 3'-IN'-ri-r3.4-Dichloro-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-ylidene]-hvdrazino}-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 258)
(Figure Removed)

This compound was prepared as described in Scheme n. 'H NMR (500MHz, DMSO-cftf) 5 13.17 (s, IH), 13.05 (s, IH), 9.47 (s, IH), 8.12 (t, 7=1.7 ,Hz, IH), 7.97-7.93 (m, 3H), 7.91 (d, 7=8.5 Hz, IH), 7.81-7.77 (m, 2H), 7.64 (dd, 7=8.5, 2.4 Hz, IH), 7.61 (t, 7=7.7 Hz, IH), 7.57 (d,7=8.5 Hz, IH), 7.18 (s, IH), 7.14 (t, 7=7.7 Hz, IH), 7.07 (dd,7=7.7, 1.6 Hz, IH).

Example 159: 3'-(N'-[l-f3.5-Dichloro-phenvl)-2-oxo-6-trifluoromethyl-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 259)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H 3NMR (300MHz, CD3OD) 5 8.13 (s, IH), 7.97 (d, >7.7 Hz, IH), 7.91 (d, .7=7.7 Hz, IH), 7.79 (rn, IH), 7.66 (d, .7=7.7 Hz, IH), 7.62-7.59 (m, 3H), 7.54-7.47 (m, 2H), 7.16-7.02 (m, 3H).
Example 160: 3-(4-(N'-ri-(3.5-Dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dih.vdro-indol-3-vlidenel-hvdrazinoi-S-hvdroxv-phenvD)--methvl-acrvlic acid (Compound 260)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H IslMR (500MHz, DMSO-40 5 13.14 (s, IH), 12.45 (s, IH), 10.61 (s, IH), 7.90 (d, .7=8.0 Hz, IH), 7.75 (d, .7=8.1 Hz, IH), 7.55-7.51 (m, 2H), 7.18 (s, IH), 7.16 (s, 2H), 7.12-7.09 (m, 2H), 6.98 (s, IH), 2.37 (s, 6H), 2.08 (d, .7=1.0 Hz, 3H).

Example 161: 3-f4-(N'-[l-(3.4-Dimethvl-phenvl)-2-oxo-6-trifluoromethvl-1.2-dihydro-indol-3-vlidene1-hvdrazmol-3-hvdroxv-phenvl)-2-methvl-acrvlic acid (Compound 261)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (300MHz, DMSO-ck) 8 13.13 (s, IH), 12.45 (s, IH), 10.61 (s, IH), 7.90 (m, IH), 7.75 (m, IH), 7.56-7.50 (m, 2H), 7.39 (m, IH), 7.33 (s, IH), 7.26 (m, IH), 7.13-7.08 (m, ,2H), 6.96 (s, IH), 2.32 (s, 3H), 2.31 (s, 3H), 2.08 (s, 3H).
Example 162: 2'-Hvdroxv-3'-[N-(2-oxo-7-phenvl-1.2-dihvdro-indol-3-vlidene)-hvdrazino'|-biphenvl-3-carboxvlic acid (Compound 262)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500MHz, DMSO-rftf) 8 13.16 (s, IH), 10.91 (s, IH), 8.15 (t, .7=1.4 Hz, IH), 7.95 (ddd, /= 7.8, 1.4, 1.2 Hz, IH), 7.79 (ddd, .7=7.8, 1.4, 1.2 Hz, 1H),7.72 (dd, J =7.9, 1.5 Hz, IH), 7.63 (dd, .7=7.6, 1.2 Hz, IH), 7.58 (t, .7=7.8 Hz, IH), 7.56-7.46 (m, 4H), 7.41 (m, IH), 7.26 (dd, .7=7.6,1.2 Hz, IH), 7.18 (t, y=7.6Hz, 1H),7.11 (t,.7=7.9Hz, IH), 6.99(dd,7=7.9,1.5 Hz, IH).

Example 163: 3'- fN'-[ 1 -(3.4-Dimethvl-phenvl)-2-oxo-6-trifluoromethoxv-1.2-dihvdro-mdol-3 -vlidene1-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 263)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500MHz, DMSO-^) 5 13.27 (s, IH), 13.02 (s, 1H),9.39 (s, 1H),8.12 (s, IH), 7.95 (m, IH), 7.80 (m, IH), 7.65-7.58 (m, 2H), 7.42-7.24 (m, 4H), 7.22-7.11 (m, 2H), 7.04 (m, 1H),6.89 (m, IH), 2.32 (s, 3H), 2.30 (s, 3H).
Example 164: 3'-fN'-[l-(3.4-Dimethvl-phenvlV2-oxo-6-rL1.2.2-tetrafL\ioro-ethoxvV1.2-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 264)
(Figure Removed)
This compound was prepared as described in Scheme H *H NMR (500MHz, DMSO) 5 13.07 (s, IH), 13.04 (s, IH), 9.33 (s, IH), 8.12 (t, .7=1.6 Hz, IH), 7.94 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.80 (d, 7=8.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.74 (dd, 7=7.8, 1.6 Hz, IH), 7.60 (t, 7=7.7 Hz, IH), 7.37 (d, 7=8.1 Hz, IH), 7.32 (d, 7=2.0 Hz, I H), 7.25 (dd, 7=8.1, 2.0 Hz, IH), 7.12 (t, 7=7.8 Hz, IH), 7.09 (dd, 7=8.2, 2.1 Hz, IH), 7.02 (dd, 7==7.8, 1.6 Hz, IH), 6.78 (tt, 7=52.1, 3.1 Hz, IH), 6.63 (d, 7=2.1 Hz, IH), 2.32 (s, 3H), 2.30 (s, 3H).

Example 165: 3'-fN'-|'l-('3.4-Dimethvl-phenvn-5-methvl-2-oxo-l .2-dihvdro-indol-3-vlidene1-hydrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 265)

(Figure Removed)
This compound was prepared as described in Scheme tl. !H NMR (500 MHz, §13.04 (s, 2H), 9.26 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.94 (ddd, -7=7.7, 1.6, 1.2 Hz, IH), 7.78 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.72 (dd, 7=7.9, 1.6 Hz, IH), 7.59 (t, .7=7.7 Hz, IH), 7.55 (s, IH), 7.34 (d, 7=8.1 Hz, IH), 7.28 (d, 7=2.0 Hz, IH), 7.22 (dd, 7=8.1, 2.0 Hz, IH), 7.11 (t, 7=7.9, Hz, IH), 7.09 (m, IH), 6.99 (dd, 7=7.9, 1.6 Hz, IH), 6.76 (d, 7=8.0 Hz, IH), 2.37 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H).
Example 166: 3'-{N'-[l-(4-Isopropvl-phenvl)-5-methvl-2-oxo-1.2-dihvdro-indol-3-vlidene]-hvdrazmo-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 266)

(Figure Removed)
This compound was prepared as described in Scheme H. !H NMR (500 MHz, DMSO-rfff) §13.03 (s, 2H), 9.26 (s, IH), 8.11 (t, 7=1.6 Hz, IH), 7.94 (ddd, J=7.7,1.6, 1.2 Hz, IH), 7.79 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.72 (dd, 7=7.9, 1.6 Hz, IH), 7.59 (t, .7=7.7 Hz, IH), 7.56 (s, IH), 7.46 (d, 7=8.6 Hz, 2H), 7.43 (d, 7=8.6 Hz, 2H), 7.1 l(t, 7=7.9 Hz, IH), 7.10 (m, IH), 6.99 (dd, 7=7.9, 1.6 Hz, IH), 6.79 (d, 7=8.2 Hz, IH), 3.00 (sept, 7=6.9 Hz, IH), 2.37 (s, 3H), 1.26 (d, 7=6.9 Hz,6H).

Example 167: 3'-(N'-[l-f3.4-Dimethyl-phenvlV6-phenvl-2-oxo-l .2-dihvdro-indol-3-vlidene1-hvdrazmo}-2'-hvdroxv-brohenvl-3-carboxvlic acid (Compound 267)



(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-ck) 813.10 (s, IH), 13.05 (s, IH), 9.30 (s, IH), 8.13 (t,7=l .6 Hz, IH), 7.95 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.81 (d, .7=7.8 Hz, IH), 7.80 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.75 (dd, J=7.9, 1.5 Hz, IH), 7.62-7.57 (m, 3H), 7.48 (dd, 7=7.8, 1.8 Hz, IH), 7.47-7.42 Cm, 2H), 7.39-7.34 (m, 3H), 7.30 (dd, 7=7.8, 2.2 Hz, IH), 7.13 (t, .7=7.9 Hz, IH), 7.02-7.00 (m, 2H), 2.32 (s, 3H), 2.31 (s, 3H).
Example 168: 3'-(N'-[l-f3-Trifluoromethvl-phenyl')-6-trifluorom.ethyl-2-oxo-1.2-dihvdro-indol-3-Ylidenel-hvdrazinol-2'-hvdroxv-biplienvl-3-carboxvlic acid CComDound 268)
(Figure Removed)
This compound was prepared as described in. Scheme EL 'H NMR (500 MHz, DMSO-dtf) ^13.19 (s, IH), 13.05 (s, IH), 9.47 (s, IH), 8.12 (t, 7==1.7 Hz, IH), 8.03 (s, IH), 7.97-7.93 (m, 3H), 7.93-7.86 (m, 2H), 7.80 (dd, 7=7.8,1.6 Hz, IH), 7.80 (ddd, 7=7.8,1.7, 1.2 Hz, IH), 7.61 (t, 7=7.8 Hz, IH), 7.58 (dq, 7=7.8, 0.8 Hz, IH), 7.15 (t, 7=7.8 Hz, IH), 7.10 (d, 7=0.7 Hz, IH), 7.08 (dd, 7=7.8, 1.6 Hz, IH).

Example 169: 3t-IN'-[l-(4-Trifluoromethoxv-phenvl')-5-trifluoromethoxv-2-oxo-l .2-dihydro-indol-3-vlidene1-hvdrazino-2'-hvdroxv-biphenyl-3-carboxvlic acid (Compound 269)
(Figure Removed)
This compound was prepared as described in Scheme EL 'H NMR (500 MHz, .10 (s, IH), 13.05 (s, IH), 9.40 (s, IH), 8.12 (t, 7=1.6 Hz, IH), 7.95 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.82 (dd, 7=7.8,1.6 Hz, IH), 7.80 (ddd, 7=7.7, 1.6, 1.2 Hz, IH), 7.74 (m, IH), 7.73 (d, 7=9.0 Hz, 2H), 7.62 (dq, 7=9.0, 0.9 Hz, 2H), 7.60 (t, 7=7.7 Hz, IH), 7.28 (ddq, 7=8.6, 2.1, 0.9 Hz, IH), 7.13 (t, 7=7.8 Hz, IH), 7.05 (dd, 7=7.8,1.6 Hz, IH), 7.02 (d, 7=8.6 Hz, IH).
Example 170: 3'--fN'-ri-f3.5-Dimethyl-phenvD-6-trifluoromethvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 270)

(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (500 MHz, DMSO-d6) £13.24 (s, IH), 13.05 (s, IH), 9.43 (s, IH), 8.12 (t, 7=1.7 Hz, IH), 7.95 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.93 (d, 7=7.8 Hz, IH), 7.80 (ddd, 7=7.7, 1.7, 1.2 Hz, IH), 7.78 (dd, 7=7.7, 1.7 Hz, IH), 7.61 (t, 7=7.7 Hz, IH), 7.54 (dq, 7=7.8, 0.8 Hz, IH), 7.18-7.16 (m, 3H), 7.14 (t, 7=7.7 Hz, IH), 7.07 (dd, 7=7.7,1.7 Hz, IH), 6.98 (m, IH), 2.37(s, 3H), 2.37 (s, 3H).

Example 171: 3'-{N'-[l-(3-Trifluoromethyl-phenvn-4.6-dimethvl-2-oxo-1.2-dihvdro-mdol-3-vlidene1-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 271)

(Figure Removed)
This compound was prepared as described in Scheme II. ]H NMR (500 MHz, £13.04 (s, IH), 13.03 (s, IH), 9.23 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 7.95 (m, IH), 7.94 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.89-7.83 (m, 3H), 7.79 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.61 (dd, .7=8.1, 1.4 Hz, IH), 7.60 (t, /=7.7 Hz, IH), 7.12 (t, .7=7.8 Hz, IH), 6.98 (dd, .7=7.8, 1.6 Hz, IH), 6.87 (s, IH), 6.57 (s, IH), 2.65 (s, 3H), 2.29 (s, 3H).
Example 172: 3'-IN'-[l-(3-Trifluoromethvl-phenvl)-5.6-dimethyl-2-oxo-1.2-dihydro-indol-3-vlidene]-hvdrazino-2'-hvdroxy-biphenvl-3-carboxvlic acid (Compound 272)
(Figure Removed)
This compound was prepared as described in Scheme H :H NMR (500 MHz, 513.04 (s, IH), 12.91 (s, IH), 9.25 (s, IH), 8.12 (t, .7=1.7 Hz, IH), 7.95 (m, IH), 7.94 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.90-7.84 (m, 3H), 7.79 (ddd, .7=7.7, 1.7, 1.2 Hz, IH), 7.71 (dd, .7=8.0,1.4 Hz, IH), 7.60 (t, .7=7.7 Hz, IH), 7.55 (s, IH), 7.11 (t, .7=7.8 Hz, IH), 6.99 (dd, .7=7.8,1.6 Hz, IH), 6.76 (s, IH), 2.29 (s, 3H), 2.25 (s, 3H).

Example 173: 3'-IN'-[l-f3.5-Diniethvl-phenvn-6-trifluoromethvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazinol-2'-hvdroxv-5'-chloro-4-fluQro-biphenvl-3-carboxvlic acid (Compound 273)

(Figure Removed)
This compound was prepared as described, in Scheme II. 'H NMR (500 MHz, DMSO-dtf) ^13.39 (s, IH), 13.11 (s, IH), 9.69 (s, 1H), 8.02 (d, .7=8.0 Hz, IH), 8.02 (dd, 7=7.0, 2.5 Hz, IH), 7.81 (ddd, 7=8.5, 4.6, 2.5 Hz, IH), 7.76 (d, 7=2.6 Hz, IH), 7.54 (dq, 7=8.0, 0.7 Hz, IH), 7.43 (dd, 7=10.7, 8.5 Hz, IH), 7.17 (s, IH), 7.16 (s, 2H), 7.08 Example 174: 3'-(N'-[l-(;3.5-Dimethyl-phenvl)-6-trifluoromethvl-2-oxo-1.2-dihvdro-indol-3-vlidene1-hvdrazino)-2'-hvdroxv-4-fluoro-biDhenvl-3-carboxvlic acid (Compound 2741


(Figure Removed)
This compound was prepared as described in Scheme II. !H NMR (500 MHz, .35 (s, IH), 13.23 (s, IH), 9.44 (s, IH), 8.01 (dd, 7=7.2, 2.4 Hz, IH), 7.92 (d, 7=8.0 Hz, IH), 7.79 (ddd, 7=8.6, 4.6, 2.4 Hz, IH), 7.79 (dd, 7=7.8,1.5 Hz, IH), 7.54 (dq, 7=8.0, 0.8 Hz, IH), 7.42 (dd, 7=10.7, 8.6 Hz, IH), 7.17 (s, IH), 7.16 (s, 2H), 7.13 (t, 7=7.8 Hz, IH), 7.05 (dd, 7=7.8, 1.5 Hz, IH), 6.98 (s, IH), 2.37 (s, 6H).

Example 175: 3'-W-[6-Chloro-l-r3.4-dimethvl-phenvl)-2-o3CO-1.2-dihvdro-indol-3-vlidenel-hvdrazino}-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 275)
(Figure Removed)
This compound was prepared as described in Scheme II. *H NMR (500 MHz, DMSO-40 § 13.06 (s, IH), 13.00 (s, IH), 9.33 (s, IH), 8.12 (s, IH), 7.94 (m, IH), 7.81-7.70 (m, 3H), 7.60 (t, .7=7.9 Hz, IH), 7.37 (d, 7=8.4 Hz, IH), 7.31 (m, IH), 7.27-7.21 (m, 2H), 7.12 (t, 7=7.8 Hz, IH), 7.02 (d, 7=7.8, IH), 6.79 (m, IH), 2.31 (s, 3H), 2.31 (s, 3H).
Example 176: 3'-W-[5-Fluoro-2-oxo-l-(4-propvl-phenyl)-l .2-dihvdro-indol-3-vlidene]-hvdrazinol-2'-hvdroxv-biphenvl-3-carboxvllc acid (Compoun-d 276)
(Figure Removed)
This compound was prepared as described in Scheme H 1H NMR (300 MHz, acetone-4) § 8.19 (t, 7=1.5 Hz, IH), 8.03 (m, IH), 7.83 (dd, 7=7.8, 1.6 Hz, IH), 7.77 (m, IH), 7.59 (t, 7=7.6 Hz, IH), 7.53 (dd, 7=8.3, 2.6 Hz, IH), 7.47 (d, 7=8.8 Hz, 2H), 7.43 (d, 7=8.8 Hz, 2H), 7.13 (t, 7=7.8 Hz, IH), 7.06-7.02 (m, 2H), 6.92 (dd, 7=8.8, 4.3 Hz, IH), 2.69 (dd, 7=7.9, 7.3 Hz, 2H), 1.71 (m, 2H), 0.98 (t, 7=7.3 Hz, 3H).

Example 177: 3'-W-r5-Cvano-l-(3.4-dimethvl-phenvlV2-oxo-1.2-dihvdro-mdol-3-vlidene1-hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid TCompound 277^
(Figure Removed)
This compound was prepared as described in Scheme H 'H NMR (300 MHz, methanol-rf,) £ 8.46 (s, IH), 8.14 (m, IH), 8.05 (s, IH), 7.99 (d, .7=7.6 Hz, IH), 7.82 (dd, .7=7.7, 1.4 Hz, IH), 7.70 (d, .7=7.6 Hz, IH), 7.58 (m, IH), 7.52 (t, .7=7.6 Hz, IH), 7.36 (m, IH), 7.25 (s, IH), 7.19 (m, IH), 7.10 (t, .7=7.7 Hz, IH), 7.03 (dd, J=7.7,1.4 Hz, IH), 6.99 (m, IH), 2.36 (s, 6H).
Example 178: 3l-(JV-[6-Chloro-l-(3.5-dimethvl-phenvlV2-oxo-1.2-dihvdro-indol-3-ylidene]-hvdrazinol-2'-hvdroxv-bir>henvl-3-carboxvlic acid (Compound 278~>

(Figure Removed)
was prepared as described in Scheme n. !H NMR (300 MHz, acetone-rftf) 8.13.22 (s, IH), 8.49 (s, IH), 8.19 (t, ,7=1.6 Hz, IH), 8.04 (ddd, .7=7.7, 1.6, 1.2 Hz, IH), 7.82-7.77 (m, 2H), 7.76 (d,/=8.0 Hz, IH), 7.61 (t, .7=7.7 Hz, IH), 7.21 (dd, 7=8.0, 1.8 Hz, IH), 7.19-7.15 (m, 3H), 7.13 (t, .7=7.7 Hz, IH), 7.04 (dd, 7=7.7, 1.6 Hz, IH), 6.90 (d, .7=1.8 Hz, IH), 2.40 (s, 6H).

Example 179: 4-Fluoro-3'-W-[l-(3-fluoro-4-methvl-phenyl)-2-oxo-6-trifluoromethvl-1.2-dihvdro-indol-3-vlidene1-hvdrazino-2'-hvc3roxv-biphenvl-3-carboxvlic acid (Compound 279)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (300 MHz, acetone-d«) £ 8.09 (dd, 7=7.0, 2.4 Hz, IH), 7.96 (d, .7=7.9 Hz, IH), 7.85 (dd, 7=7.8, 1.6 Hz, IH), 7.80 (ddd, .7=8.5, 4.5, 2.4 Hz, IH), 7.57-7.50 (m, 2H), 7.44-7.32 (m, 3H), 7.20 (m, IH), 7.15 (t, .7=7.8, IH), 7.07 (dd, .7=7.8,1.6 Hz, IH), 2.37 (d, J=l .9 Hz, 3H).
Example 180: 3'-(A/1-ri-f4-Chloro-3.5-dirnethvlphenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino-2'-hvdroxv-biphenvl-3-carboxvlic acid (Compound 280)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, CDC13) 7.75 (s, IH), 7.45-7.41 (m, 2H), 7.39 (m, IH), 7.09 (m, IH), 3.25 (t, J= 7.3, 2H), 3.03 (t, /= 7.3,2H), 1.81 (sext, J= 7.3, 2H), 1.63 (sext, /= 7.3, 2H), 1.12 (t, /= 7.3, 3H), 1.01 (t, J = 7.3,3H).
Example 181: 3'-W-[l-(3.5-Dimethylphenvn-4-fluoro-2-oxo-6-trifluoromethyl-1.2-dihvdroindol-3-vlidene1hvdrazinol-2'-hvdroxvbiphenvl-4-fluoro-3-carboxvlic acid (Compound 281)


(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO-dtf) 13.35 (s, IH), 8.01 (dd, J= 7.1, 2.4, IH), 7.78 (ddd, J= 8.5, 4.5, 2.4, IH), 7.66 (dd, /= 7.9, 1.6, IH), 7.50 (d, /= 9.4, IH), 7.41 (dd, J= 10.7, 8.5, IH), 7.18 (s, IH), 7.15 (s, 2H), 7.14 (t,J = 7.9, IH), 7.07 (dd, J= 7.9, 1.6, 1H),6.83 (q, J= 0.7, IH), 2.37 (s, 6H).
Example 182: 3'- W-[ 1 -BenzoF 1.31dioxo-5-vl-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino-2'-hvdroxybiphenvl-3-carboxvlic acid ("Compound 282^
(Figure Removed)
This compound was prepared as described in Scheme H JH NMR (500 MHz, DMSO-4,) 13.21 (s, IH), 13.05 (s, IH), 9.43 (s, IH), 8.12 (t, J= 1.6, IH), 7.95 (ddd, J= 7.7, 1.6, 1.2, IH), 7.92 (d, J= 7.8, IH), 7.80 (dd, /= 7.7, 1.6, 1.2, IH), 7.78 (dd, J= 7.9, 1.6, IH), 7.60 (t, J - 7.7, IH), 7.54 (dq, J= 7.8, 0.8, IH), 7.18 (d, 7 = 2.1, IH), 7.14 (d, /= 8.2, IH), 7.14 (t,J= 7.9, IH), 7.06 (dd,/= 7.9,1.6, IH), 7.03 (dd,/= 8.2,2.1, IH), 6.98 (q, J= 0.6, IH), 6.16 (s, 2H).

Example 183: 3'- N-F1 -Benzof 1.31dioxo-S-vl-2-oxo-6-trifluoromethvl-l .2-dihvdromdol-3-vlidene1hvdrazino}-2'-hvdroxvbit)henvl-2-fluoro-3-carboxvlic acid (Compound 283~)
(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, DMSO- Example 184: 3'-N-ri-f3.5-Dimethylphenyl)-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino-2'-hvdroxvbiphejavl-2-hvdroxv-3-carboxvlic acid (Compound 2841)
(Figure Removed)
This compound was prepared as described in Scheme H :H NMR (500 MHz, 13.23 (s, IH), 9.31 (s, IH), 7.97 (d, J = 2.3, IH), 7.92 (d, J= 7.9, IH), 7.73 (dd, 7= 7.8, 1.5, IH), 7.69 (dd, J= 8.6, 2.3, IH), 7.54 (dq, J= 7.9,0.7, IH), 7.17 (s, IH), 7.16 (s, 2H), 7.10 (t, J = 7.8, IH), 7.06 (d, J= 8.6, IH), 7.02 (dd, J= 7.8,1.5, IH), 6.98 (d, J= 0.9, IH), 2.37 (s, 6H).


Example 185: 3'-N-[ 1 -(3 -Methoxvcarbonvlphenvl )-2-oxo-6-tri fluoromethvl-1.2-dihvdroindol-3-Ylidene1hvdrazino}-2'-hvdroxvbithenvl-3-carboxylic acid fCompound 285")

(Figure Removed)
This compound was prepared as described in Scheme II. 'H NMR (500 MHz, 13.20 (s, IH), 13.05 (s, IH), 9.45 (s, IH), 8.15 (t, J= 1.7, IH), 8.12 (t,J= 1.7, IH), 8.10 (ddd, J= 7.8, 1.7, 1.2, IH), 7.95 (m, 2H), 7.90 (m, IH), 7.80 (t, ./= 7.8, IH), 7.82-7.78 (m, 2H), 7.61 (t, 7= 7.8, IH), 7.57 (dq, J= 7.9, 0.8, IH), 7.15 (t, J= 7.8, IH), 7.08 (m, IH), 7.07 (dd, J = 7.8,1.6, IH), and 3.90 (s,3H).
Example 186: 3-'N-[l-(3-MethoxvcarbonvlphenvD-2-oxo-1.2-dihvdroindol-3-vlidene]hvdrazino-2'-hydroxvbiphenyl-3-carboxylic acid (Compound 286~)
(Figure Removed)
This compound was prepared as described in Scheme n. 'H NMR (500 MHz, DMSO-4) 13.04 (s, IH), 9.30 (s, IH), 8.12 (t, J= 1.7, IH), 8.12 (t, J= 1.7, IH), 8.06 (ddd, J= 7.8, 1.7, 1.2, IH), 7.94 (ddd, J = 7.8, 1.7, 1.2, IH), 7.88 (m, IH), 7.80 (ddd, J = 7.8, 1.7, 1.2, IH), 7.77 (t, J=7.8, IH), 7.76 (dd, J= 7.6,0.8, IH), 7.74 (dd,/= 7.8,1.6, IH), 7.60 (t,.7= 7.8Hz, IH), 7.31

(td, J= 7.6, 1.3, IH), 7.22 (td, J= 7.6, 0.8, IH), 7.12 (t, J= 7.8, IH), 7.01 (dd,/= 7.8, 1.6, IH), 6.95 (d, J= 7.6, IH), 4.11 (s, IH) and 3.90 (s, 3H).
Example 187: 3'-N-[7-A2a-l-G.4-dimethvlphenylV2-oxo-1.2-dihvdroindol-3-vlidene1hvdrazino-2'-hvdroxvbit)henvl-3-carboxvlic acid (Compound 287)

(Figure Removed)

This compound was prepared as described in Scheme I. 'H NMR (500 MHz, DMSO-4,) 13.10 (s, IH), 13.04 (s, IH), 9.36 (s, IH), 8.16 (dd, J= 5.1, 1.6 Hz, IH), 8.12 (t, J= 1.6 Hz, IH), 8.04 (dd, J= 7.4,1.6 Hz, IH), 7.94 (ddd, J= 7.7, 1.6, 1.2 Hz, IH), 7.80 (ddd, /= 7.7,1.6, 1.2 Hz, IH), 7.74 (dd, J = 7.8,1.6 Hz, IH), 7.6O (t, J= 7.7 Hz, IH), 7.34 (d, J = 1.8 Hz, IH), 7.30 (d, J= 8.1 Hz, IH), 7.28 (dd, /= 8.1, 1.8 Hz, IH), 7.21 (dd, J= 7.4, 5.1 Hz, IH), 7.13 (t, J= 7.8 Hz, IH), 7.03 (dd, J= 7.8,1.6 Hz, IH), 2.30 (s, 3H), 2.29 (s, 3H).
Example 188: 3'-W-ri-(3.5-Dimethvlphenvl)-2-oxo-1.2-dihvdroindol-6-trifluoromethyl-3-vlidene1hvdrazino}-2'-hYdroxvbit)henvl-3-(2-methvl-2-DroDionic acid") (Compound 288

(Figure Removed)
This compound was prepared as described in Scheme I. JH NMR (500 MHz, DMSO-cftf) 13.25 (s, IH), 12.39 (s, IH), 9.35 (s, IH), 7.92 (d, J= 7.8 Hz, IH), 7.75 (dd, J= 8.0,1.5 Hz, IH), 7.56-7.53 (m, 2H), 7.46-7.42 (m, 2H), 7.35 (m, IH), 7.17 (s, 3H), 7.12 (t, J= 7.8 Hz, IH), 7.02 (dd, J= 7.8, 1.6 Hz, IH), 6.99 (q, J= 0.7 Hz, IH), 2.37 (s, 6H), 1.52 (s, 6H).



Example 189: 3'-(N-[1.3-N.N-Ditnethvlbarbitur-5-vlidene]hvdrazino}-2'-hvdroxvbiphenvl-3-carboxvlic acid (Compound 2891
(Figure Removed)
This compound was prepared as described in Scheme I. 'H NMR (500 MHz, DMSO-cQ 8.14 (t, J = 1.3 Hz, IH), 7.95 (d, J= 7.7 Hz, IH), 7.81 (dt, /= 7.7, 1.3 Hz, IH), 7.65 (d, J=7.7Hz, 1H),7.61 (t, .7=7.7 Hz, IH), 7.18 (dd,J= 7.7, 1.2 Hz, IH), 7.13 (m, IH), 3.22 (s, 6H).
Example 190: 3'-(N-[l-N-(4-Trifluoromethvlbenzyl)-2.8-dioxo-l,2.7.8-tetrahvdroisoquinolm-7-vlidene1hvdrazinol-2'-hvdroxvbirhenvl-3-carboxvlic acid (Compound 290)
(Figure Removed)
This compound was prepared as described in Scheme I. 'H NMR (500 MHz, DMSO-40 14.24 (s, IH), 13.06 (s, IH), 9.49 (s, 1H), 8.36 (d, J= 7.9 Hz, IH), 8.16-8.12 (m, 2H), 7.95 (d, J= 7.7 Hz, IH), 7.88 (dd, J= 7.8, 1.0 Hz, IH), 7.84-7.79 (m, 2H), 7.68 (d, J= 8.2 Hz, 2H), 7.61 (t, J = 7.7 Hz, IH), 7.58 (d, J= 8.2 Hz, 2H), 7.55 (td, J= 7.7, 0.9 Hz, IH), 7.15 (t, J= 7.8 Hz, IH), 7.10 (dd, J = 7.8,1.0 Hz, IH), 5.28 (s, 2H).

Example 191: 3'-N-[l-N-(4-Methvlbenzvn-2.8-dioxo-1.2.7,8-tetrahvdroisoquinolin-7-vlidene1hvdrazino}-2'-hvdroxvbiphenvl-3-carboxylic acid (Compound 291)
(Figure Removed)
This compound was prepared as described in Scheme I. *H NMR (500 MHz, DMSO-flffi) 14.28 (s, IH), 13.06 (s, IH), 9.49 (s, IH), 8.34 (d, J= 8.0 Hz, IH), 8.15-8.12 (m, 2H). 7.96 (dm, J = 7.8 Hz, IH), 7.87 (dm, J= 7.8 Hz, IH), 7.82-7.78 (m, 2H), 7.61 (t, J= 7.8 Hz, IH), 7.54 (td, J= 7.7, 0.9 Hz, IH), 7.25 (d, J= 8.2 Hz, 2H), 7.15 (t, J= 7.8 Hz, IH), 7.10 (m, IH), 7.12 (d, J= 8.2 Hz, 2H), 5.16 (s, 2H), 2.25 (s, 3H).
Example 192: 3'-{N-[l-N-Benzyl-2.8-dioxo-1.2.7.8-tetrahydToisoquinolm-7-ylidene]hvdrazinol-2'-hvdroxvbiphenvl-3-carboxvlic acid (Compound 292)
(Figure Removed)
This compound was prepared as described in Scheme I. *H NMR (500 MHz, 14.28 (s, IH), 13.06 (s, IH), 9.49 (s, IH), 8.35 (d, J= 7.9 Hz, IH), 8.16-8.12 (m, 2H), 7.95 (dd, J = 7.7,1.2 Hz, IH), 7.88 (d, J= 7.8 Hz, IH), 7.82-7.78 (m, 2H), 7.61 (t, J - 7.7 Hz, IH), 7.55 (td, J= 7.6, 0.8 Hz, IH), 7.36 (d, J= 7.4 Hz, 2H), 7.32 (t, J= 7.4 Hz, 2H), 7.25 (t, /= 7.4 Hz, IH), 7.15 (t, J= 7.8 Hz, IH), 7.10 (dd, J= 7.8,1.2 Hz, IH), 5.21 (s, 2H).

Example 193: 3'-(N-|'l-N-(4-Trifluorome1:hylphenyn-2.8-dioxo-l.2.7.8-tetrahvdroisoquinolin-7r vlidene1hvdrazmo}-2'-hvdroxvbiphenvl-3-carboxvlic acid (Compound 293)
(Figure Removed)
This compound was prepared as described in Scheme I. 1H NMR (500 MHz, DMSO- Example 194: 3'-(N-f 1 -N-(3-TrifluoromethvlphenvlV2.8-dioxo-l.2.7.8-tetrahvdroisoquinolin-7-vHdenc1hvdrazmo}-2'-hvdroxvbiphenvl-3-carboxvlic acid ("Compound 294)
(Figure Removed)
This compound was prepared as described in Scheme I. :H NMR (500 MHz, 14.11 (s, IH), 13.05 (s, IH), 9.41 (s, IH), 8.42 (d, J= 7.9 Hz, IH), 8.15-8.11 (m, 2H), 7.95 (dm, J= 7.7 Hz, IH), 7.92-7.83 (m, 4H), 7.81-7.77 (m, 2H), 7.75 (d, J= 7.7 Hz, IH), 7.61 (t, J = 7.7 Hz, IH), 7.58 (td, J = 7.5,1.0 Hz, IH), 7.17 (t, J= 7.8 Hz, IH), 7.09 (dd, J= 7.8, 1.2 Hz, IH).

Example 195: 3'-N-[ 1 -N-(3.5-DimethvlphenvD-2.8-dioxo-1.2 J.8-tetrahvdroisoquinolm-7-vlidene1hvdrazino-2'-hvdroxvbiphenvl-3-carboxvlic acid (Compound 295")
(Figure Removed)
This compound was prepared as described in Scheme I. !H NMR (500 MHz, 14.18 (s, IH), 13.06 (s, IH), 9.38 (s, IH), 8.38 (dd, /= 7.6, 0.9 Hz, IH), 8.12-8.09 (m. 2H), 7.94 (dt, J= 7.7, 1.4 Hz, IH), 7.88 (dd, J = 7.9, 1.3 Hz, IH), 7.82 (td, J = 7.6, 0.9 Hz, IH), 7.78 (dt,y= 7.7, 1.4Hz, IH), 7.60(t,/= 7.7 Hz, IH), 7.56 (td,.7=7.6, 0.9 Hz, IH), 7.15 (t,J= 7.9 Hz, IH), 7.10 (s, IH), 7.08 (dd, J= 7.9, 1.3 Hz, IH), 6.96 (s, 2H), 2.32 (s, 6H).
Example 196: 3'-N-[l-N-Phenyl-2.8-dioxo-1.2.7.8-tetrahvdroisoqumolin-7-vlidene]hydrazino>-2'-hvdroxvbiphenvl-3-carboxvlic acid (Compound 296)
(Figure Removed)
This compound was prepared as described in Scheme I. *H NMR (500 MHz, 14.16 (s, IH), 13.04 (s, IH), 9.38 (s, IH), 8.40 (dd, J= 7.7, 0.9 Hz, IH), 8.14-8.10 (m, 2H), 7.94 (dt, J= 7.7, 1.4 Hz, IH), 7.89 (dd, J = 7.8, 1.3 Hz, IH), 7.83 (td, J= 7.7, 0.9 Hz, IH), 7.78 (dt, J= 7.7,1.4 Hz, IH), 7.60 (t, J= 7.7 Hz, IH), 7.57 (td, J= 7.7, 0.9 Hz, IH), 7.53 (t, /= 7.5 Hz, 2H), 7.47 (t, J= 7.5 Hz, IH), 7.38 (m, 2H), 7.15 (t, J = 7.8 Hz, IH), 7.08 (dd, J= 7.8, 1.3 Hz, IH).

Example 197: 3'-N-ri-N-(3.4-Dimethvlphenvn-2.8-dioxo-1.2.7.8-tetrahvdroisoqui3iolin-7-vlidene1hvdrazino}-2'-hvdroxvbiphenvl-3-carboxylic acid (Compound 297)
(Figure Removed)
This compound was prepared as described in Scheme I. 'H N\dR (500 MHz, 14.19 (s, IH), 13.04 (s, IH), 9.39 (s, IH), 8.41 (dd, 7 = 7.6, 0.9 Hz, IH), 8.14-8.10 (m, 2H), 7.94 (dt, /= 7.6, 1.4 Hz, IH), 7.90 (dd, J = 7.8, 1.2 Hz, IH), 7.85 (td, J = 7.6, 0.9 Hz, IH), 7.78 (dt, J= 7.6,1.4 Hz, IH), 7.60 (t, 7= 7.6 Hz, IH), 7.57 (td, J= 7.6,0.9 Hz, IH), 7.27 (d, J = 7.4 Hz, IH), 7.22 (t, J = 7.8 Hz, IH), 7.18-7.12 (m, 2H), 7.08 (dd, J = 7.8, 1.2 Hz, IH), 2.33 (s, 3H), 1.95(s,3H).
Example 198: 3'-(N-ri-N-r3.4-Dimethvlphenvn-2-oxo-6-trifluoromethvl-1.2-dihvd.roindol-3-vlidene1hvdrazinol-2'-fluorobiphenvl-3-carboxvlic acid (Compound 298)
\(Figure Removed)
This compound was prepared as described in Scheme I. 'H NMR (500 MHz, DMSO-4) 13.06 (s, IH), 8.13 (m, IH), 8.00 (dt, J= 7.8,1.3 Hz, IH), 7.94 (d, J= 7.9 Hz, IH), 7.90 (in, IH), 7.85 (m, IH), 7.64 (t, J= 7.7 Hz, IH), 7.56 (dq, J= 7.9, 0.7 Hz, IH), 7.4Z (t, /= 7.9 Hz, IH), 7.38 (d, J= 8.0 Hz, IH), 7.32 (d, /= 2.0 Hz, IH), 7.30 (m, IH), 7.26 (dd, J= 8.0,2.0 Hz, IH), 6.95 (q, J= 0.6 Hz, IH), 2.31 (s, 3H), 2.29 (s, 3H).


Example 199: 3-f3-(N-[l-N-f3.4-Diinethvlphenvl')-2-oxo-6-trifluoromethyl-1.2Hiihvdrpindol-3-vlidene1hvdraano)-2-hvdroxvphenvl)-2(Z)-propenoic acid (Compound 299")
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-4,) 13.26 (s, IH), 8.13 (d, J = 9.6 Hz, IH), 8.03 (m, IH), 7.96 (d, J= 7.9 Hz, IH), 7.57 (dq, J= 7.9, 0.7 Hz, IH), 7.48-7.44 (m, 2H), 7.40 (d, J = 8.1 Hz, IH), 7.36 (d, J= 2.2 Hz, IK), 7.29 (dd, 7=8.1, 2.2 Hz, IH), 6.99 (m, IH), 6.59 (d, /= 9.6 Hz, IH), 2.33 (s, 3H), 2.32 (s, 3H).
Example 200: 3-(3-N-[l-N-f3.4-Dirnethylphenvl)-2-oxo-4-fluoro-6-trifluoromethyl-l .2-dihvdroindol-3-vlidene1hvdrazino-2-hvdroxvDhenvl)-2(Z)-Dropenoic acid (Compound 3 00)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-4) 13.39 (s, IH), 8.13 (d, /= 9.6 Hz, IH), 7.90 (m, IH), 7.55 (d, J = 9.5 Hz, 1H), 7.49-7.47 (m, 2H), 7.40 (d, J= 8.0 Hz, IH), 7.35 (d, J= 1.9 Hz, IH), 7.29 (dd, /= 8.0,1.9 Hz, IH), 6.84 (s, IH), 6.59 (d, J = 9.6 Hz, IH), 2.33 (s, 3H), 2.32 (s, 3H).


Example 201 : 5-(3-
dihydroindol-3-vlidene]hvdrazino}-2-hvdroxvbenzvlidene1thiazolidine-2.4-dione (Compound 301)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, 13.29 (s, IH), 8.06 (s, IH), 7.70 (m, IH), 7.50 (d, /= 9.6 Hz, IH), 7.39 (d, J= 8.1 Hz, IH), 7.32 (d, J= 2.1 Hz, IH), 7.26 (dd,J= 8.1, 2.1 Hz, IH), 7.17-7.14 (m, 2H), 6.80 (q, J= 0.7 Hz, IH), 2.33 (s, 3H), 2.31 (s, 3H).
Example 202: 2-Chloro-3-f4-(N'-['l-(3,4-dimethvlphenvn-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidenelhvdrazino l-3-hvdroxvphenvn-2-propenoic acid (Compound 302)

(Figure Removed)
This compound was prepared as described in Scheme V. ]H NMR (500 MHz, DMSO-dtf) 13.13 (s, IH), 10.74 (s, IH), 7.92 (d, J= 8.2 Hz, IH), 7.85 (s, IH), 7.77 (d, J= 8.6 Hz, IH), 7.72 (d, .7= 1.4 Hz, IH), 7-54 (d, J = 8.2 Hz, IH), 7.45 (dd, J= 8.6, 1.4 Hz, IH), 7.39 (d, J= 8.0 Hz, IH), 7.33 (d, /= 1.6 Hz, IH), 7.27 (dd, /= 8.0, 1.6 Hz, IH), 6.96 (m, IH), 2.33 (s, 3H), 2.31(s,3H).


Example 203: 2-Ethvl-3-( 4- N-[ 1 -(3.4-dimethvlphenvl -2-oxo-6-trifluorornethvl-1.2-dihydroindol-3-vlidene]hvdrazinoy-3-hvdroxvphenvl)-2-propenoic acid (Compound 303)
(Figure Removed)
This compound was prepared as described in Scheme V. ]H NMR (500 MHz, Acetone-^) 13.32 (s, IH), 10.78 (s, IH), 9.52 (s, IH), 7.95 (d, J= 7.9 Hz, 1 H), 7.87 (d, J = 8.6 Hz, IH), 7.61 (s, IH), 7.52 (d, J = 7.9 Hz, IH), 7.40 (d, J= 8.1 Hz, IH), 7.37 (br s, IH), 7.31 (br d, J= 8.1 Hz, IH), 7.21 (s, 1H), 7.16 (d, J= 8.6 Hz, IH), 7.10 (s, IH), 2.61 (q, T = 7.3 Hz, 2H), 2.37 (s, 6H), 1.20 (t, .7=7.3 Hz, 3H).
Example 204: l-N-Methvl-5-r4-W-ri-(3.5-dimethvlDhenvn-2-oxo-6-trifluioromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino}-3-hvdroxybenzvlidene)-1.3-diazolidine-2.4-dione (Compound 304)
(Figure Removed)
This compound was prepared as described in Scheme V. 'H NMR (500 MHz, DMSO-rf) 13.17 (s, IH), 13.13 (s, IH), 11.43 (s, IH), 11.35 (s, IH), 10.64- (s, IH), 10.58 (s, IH), 7.92-7.88 (m, 3H), 7.72 (d, J = 8.3 Hz, IH), 7.70 (d, J= 8.3 Hz, IH), 7.53 (am, 2H), 7.50 (d, J= 8.3 Hz, IH), 7.18 (s, 2H), 7.16 (s, 4H), 7.01 (d, J - 8.3 Hz, IH), 6.98 (m, 2H}, 6.95 (s, IH), 6.59 (s, IH), 6.35 (s, IH), 3.10 (s, 3H), 2.93 (s, 3H), 2.37 (s, 12H).

Example 205: 5-(4-N-F1 -(3.5-DimethvlphenvD-2-oxo-6-trifluoromethvl-l .2-dihvdrQindol-3-vlidenelhydrazmo'} -3 -hvdroxvbenzylidene')-1.3 -diazolidine-2.4-dione (Compound 305
(Figure Removed)
This compound was prepared as described in Scheme V. ]H NMR (500 MHz, DMSO-d6) 13.14 (s, IH), 11.21 (s, IH), 10.57 (s, IH), 10.48 (s, IH), 7.91 (d, .7=7.9 Hz, IH), 7.68 (d, J= 8.4 Hz, IH), 7.51 (d, J= 7.9 Hz, IH), 7.27 (d, J= 8.4 Hz, IH), 7.15 (s, IH), 7.14 (s, 2H), 7.05 (s, IH), 6.96 (s, IH), 6.32 (s, IH), 2.35 (s, 6H).
Example 206: 2-Fluoro-3-r4-N-ri-f3.4-dimethvlDhenv)2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino}-3-hvdroxvphenvl)-2-propenoic acid (Compound 3Q61
(Figure Removed)
This compound was prepared as described in Scheme V. *H NMR (500 MHz, DMSO-dtf) 13.56 (s, IH), 13.12 (s, IH), 10.69 (s, IH), 7.91 (d, J = 8.0 Hz, IH), 7.75 (d, J= 8.3 Hz, IH), 7.54 (d, J = 8.0 Hz, IH), 7.39 (d, J= 8.1 Hz, IH), 7.36 (s, IH), 7.33 (br s, !H),7.29-7.25 (m, 2H), 6.95 (d, J= 36.7 Hz, IH), 6.95 (m, IH), 2.33 (s, 3H), 2.31 (s, 3H).

Example 207: (±)-2-Methoxv-3-(4-N-ri-(3.5-dime1:hvlphenvn-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene1hvdrazino}-3-hvdroxyphenvDpropanoic acid (Compound 307)
(Figure Removed)
This compound was prepared as described in Scheme V. JH NMR (500 MHz, 13.10 (s, IH), 10.43 (s, IH), 7.86 (d, J= 7.9 Hz, IH), 7.59 (d, J*= 8.3 Hz, IH), 7.51 (dq, J= 7.9, 0.7 Hz, IH), 7.16 (s, IH), 7.15 (s, 2H), 6.97 (q,J= 0.6 Hz, IH), 6.83 (d, J= 1.6 Hz, IH), 6.80 (dd, J= 8.3, 1.6 Hz, IH), 3.88 (dd, 7= 8.0, 4.6 Hz, IH), 3.25 (s, 3H), 2.91 (dd, 7= 14.2, 4.6 Hz, IH), 2.80 (dd,y= 14.2, 8.0 Hz, IH), 2.37 (s, 6H).
Example 208: 4-r3-N-[l-f3.4-dimethvlphenvl)-2-oxo-6-trifluoromethvl-1.2-dihvdromdol-3-vlidene1hvdrazinol-2-hvdroxvphenvl)butanoic acid (Compound 308)
(Figure Removed)
This compound was prepared as described in Scheme V. 1H NMR (500 MHz, DMSO-dtf) 13.18 (s, IH), 12.08 (s, IH), 9.26 (s, IH), 7.89 (d, 7= 7.9 Hz, IH), 7.60 (dd, J= 7.8,1.6 Hz, IH), 7.52 (dq, J= 7.9,0.7 Hz, IH), 7.17 (s, IH), 7.16 (s, 2H), 6.96 (rn, IH), 6.95 (t, /= 7.8 Hz, IH), 6.88 (dd, J = 7.8, 1.6 Hz, IH), 2.65 (t, J = 7.6 Hz, 2H), 2.37 (s, 6H), 2.25 (t, J = 7.6 Hz, 2H), 1.77(qn,y=7.6Hz,2H).


Example 209: 3-(2- N-[l-(3.5-dimethvlphenvlV2-oxo-6-trifluoromethvl-1 .2-dihvdroindol-3-vlidene1hvdrazino)-3-hvdroxvphenoxy' propanoic acid (Compound 309)
(Figure Removed)

This compound was prepared as described in Scheme "V. 'H NMR (500 MHz, DMSO-4) 13.0 (s, 1 H), 12.4 (s, 1 H), 10.1 (s, 1 H), 7.84 (d, J= 7.8 Hz, 1 H), 7.49 (d, J= 7.8 Hz, 1 H), 7.18 (s, 1 H), 7.15 (s, 2 H), 6.99 (dd, J= 8.8, 8.8 Hz, 1 H), 6.93 (s, 1 H), 6.68 (d, J= 8.3 Hz, 1 H), 6.30 (d, J = 7.8 Hz, 1 H), 4.28-4.26 (m, 2 H), 2.77-2.75 (m, 2 H), 2.37 (s, 6 H).
Example 210: 4-(4-(N-ri-(3.4-dimethvlphenyl)-2-oxo-6-trifluoromethvl-1.2-dihvdroindol-3-vlidene]hydrazino}-3-hydroxyphenvDbutanoic acid (Compound 310)
(Figure Removed)
This compound was prepared as described in Scheme "V. 'H NMR (500 MHz, CD3OD) 7.84 (d, J= 7.8 Hz, 1 H), 7.65 (d, J= 8.4 Hz, I H), 7.44 (d, J= 7.8 Hz, 1 H), 7.18 (s, 1 H), 7.09 (s, 2 H), 6.99 (s, 1 H), 6.78 (d, /= 7.8 Hz, 1 H), 6.74 (s, 1 H), 2.60-2.57 (m, 2 H), 2.41 (s, 6 H), 2.29-2.26 (m, 2 H), 1.92-1.88 (m, 2 H).









We Claim:
1. A compound 3'-{N'-[l-(3,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo-l,2-
dihydro-indol-3 -ylidene]-hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid, of formula:
(Formula Removed)
and pharmaceutically acceptable salts thereof.
2. A pharmaceutical composition comprising a physiologically acceptable carrier, diluent, or excipient; and a compound as claimed in claim 1 for use in treating a condition selected from thrombocytopenia and a condition affecting the nervous system.

Documents:

3035-DELNP-2007-Abstract-(15-09-2011).pdf

3035-delnp-2007-abstract.pdf

3035-DELNP-2007-Claims-(03-02-2012).pdf

3035-DELNP-2007-Claims-(15-09-2011).pdf

3035-delnp-2007-claims.pdf

3035-delnp-2007-correspondence -others.pdf

3035-DELNP-2007-Correspondence Others-(03-02-2012).pdf

3035-delnp-2007-Correspondence Others-(15-03-2011).pdf

3035-DELNP-2007-Correspondence Others-(15-09-2011).pdf

3035-delnp-2007-Correspondence-Others-(27-06-2007).pdf

3035-delnp-2007-correspondence-others-1.pdf

3035-delnp-2007-description (complete).pdf

3035-DELNP-2007-Form-1-(03-02-2012).pdf

3035-DELNP-2007-Form-1-(15-09-2011).pdf

3035-delnp-2007-form-1.pdf

3035-delnp-2007-form-18.pdf

3035-DELNP-2007-Form-2-(03-02-2012).pdf

3035-DELNP-2007-Form-2-(15-09-2011).pdf

3035-delnp-2007-form-2.pdf

3035-delnp-2007-Form-3-(15-03-2011).pdf

3035-DELNP-2007-Form-3-(15-09-2011).pdf

3035-delnp-2007-form-3.pdf

3035-delnp-2007-form-5.pdf

3035-delnp-2007-pct-101.pdf

3035-delnp-2007-pct-210.pdf

3035-delnp-2007-pct-237.pdf

3035-delnp-2007-pct-304.pdf


Patent Number 255996
Indian Patent Application Number 3035/DELNP/2007
PG Journal Number 16/2013
Publication Date 19-Apr-2013
Grant Date 17-Apr-2013
Date of Filing 23-Apr-2007
Name of Patentee LIGAND PHARMACEUTICALS,INC
Applicant Address 10275 SCIENCE CENTER DRIVE, SAN DIEGO, CA 92121-1117, USA
Inventors:
# Inventor's Name Inventor's Address
1 RUPPAR, DANIEL A 18200 BLANCO SPRINGS ROAD # 1523, SAN ANTONIO, TX 78258, USA
2 ZHI, LIN 3988 VIA CANGREJO, SAN DIEGO, CA 92130, USA
3 CHEN, JYUN-HUNG 7614 PALMILLA DRIVE, # 58, SAN DIEGO, CA 92122, USA
4 DALGARD, JACKLINE E 510 STRATFORD COURT, APT. #102A, DEL MAR, CA 92014, USA
5 KALLEL, ADAM E 10160 BOULDERKNOLLS DRIVE, ESCONDIDO, CA 92026, USA
6 LAU,THOMAS 9949 SCRIPPS WESTVIEW WAY, #136, SAN DIEGO, CA 92131, USA
7 MCNEILL, MATTHEW H 249 AVENIDA DEL MAR, APT. B, SAN CLEMENTE, CA 92672, USA
8 MILLER, TODD A 1289 AVENIDA FRAGATA, SAN MARCOS, CA 92069, USA
9 NGUYEN, BAO N 11695 WESTVIEW PARKWAY, SAN DIEGO, CA 92126, USA
10 PENULAIR, RICHARD J 7740 MARGERUM AVENUE, # 101, SAN DIEGO, CA 92120, USA
11 PHILLIPS, DEAN P 749 CAMINO MAGNIFICO, SA MARCOS, CA 92069, USA
PCT International Classification Number C07D 277/54
PCT International Application Number PCT/US2005/038055
PCT International Filing date 2005-10-21
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/621,879 2004-10-25 U.S.A.
2 60/675,001 2006-04-25 U.S.A.