Title of Invention	"TRICYCLIC QUINOLINONE OR QUINOLINE-2(1H)-THIONE COMPOUNDS AS ANDROGEN RECEPTOR MODULATOR COMPOUNDS AND USES THEREOF"
Abstract	A tricyclic quinolinone or quinoline-2(lH)-thione of formula I: are as herein described.

Full Text

The present invention relates to tricyclic quinolinone or quinoline-2(lH)-thione compounds as androgen receptor modulator compounds and uses thereof. Background of the Invention Intracellular receptors (IRs) form a class of structurally-related genetic regulators scientists have named "ligand dependent transcription factors." R.M. Evans, Science, 240:889 (1988). Steroid receptors are a recognized subset of the IRs, including the progesterone receptor (PR) androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Regulation of a gene by such factors requires both the IR itself and a corresponding ligand, which has the ability to selectively bind to the IR in a way that affects gene transcription. A compound that binds an IR and mimics the effect of the native ligand is referred to as an "agonist", while a compound that inhibits the effect of the native ligand is called an "antagonist." The term "modulators" refers to compounds that are agonists, partial agonists or antagonists. The effectiveness of known modulators of steroid receptors is often tempered by their undesired side-effect profile, particularly during long-term administration. For example, the effectiveness of progesterone and estrogen agonists, such as norgestrel and diethylstlbesterol, respectively, as female birth control agents must be weighed against the increased risk of breast cancer and heart disease to women taking such agents. Similarly, the progesterone antagonist, mifepristone (RU486), if administered for chronic indications, such as uterine fibroids, endometriosis and certain hormone-dependent cancers, could lead TO homeostatic imbalances in a patient due to its inherent crossreactivity as a GR antagonist. Accordingly, identification of compounds that have good specificity for one or more steroid receptors, but have reduced or no cross-reactivity for other steroid or mtracellular receptors, would be of significant value in the treatment of male and female hormone responsive diseases. A group of quinolmone and coumarin analogs having a fused ring system of the aryl, piperidme. pyrrolidine, or indoline series have been described as androgen modulators. See U. S. Patent No. 5,696,130; Int. Patent Appl. WO 97/49709; L.G. Hamann, et al. ,/. Med. Chem., 41:623-639 (1998); J. P. Edwards, et al.,Bioorg. Med. Chem. /.err., S:745-750 (1998); J. P. Edwards, et al.,Bioorg. Med. Chem. Lett., 9:1003- 1008 (1999), R. I. Higuchi, et al., Bioorg. Med. Chem. Lett., 9:1335-1340 (1999). The entire disclosures of the publications and references referred to above and hereafter in this specification are incorporated herein by reference and are not admitted to be prior art. Summary of the Invention The present invention is directed to androgen receptor modulator compounds. This invention is also directed to pharmaceutical compositions containing such compounds as weii as methods of using such compounds and pharmaceutical compositions for modulating processes mediated by steroid receptors. More particularly, the invention relates to non-steroidal compounds that are high-affinity, high-specificity agonists, partial agonists (i.e.. partial activators and/or tissue-specific activators) and antagonists for androgen receptors (AR). Also provided are methods of making such compounds and pharmaceutical compositions, as well as intermediates used in their synthesis. Compounds of the present invention are represented by those having the formula: (Figure Removed) wherein: R1 is selected from the group of hydrogen, F, Cl, Br, I, NO2, OR9, NR10Rn, S(O)nRC'- Ci - C8 alkyl, C, - C8 haloalkyl, Q - Cg heteroalkyi, C3 - C8 cycloalkyl, aryl, arylalkyl, hfteroaryl, C2 - Cs alkynyl and C? - Cs alkenyl, wherein the alkyl, haloalkyl, heteroalkyi. cycloalkyl, aryl, arylalk"1-'], heteroaryl, alkynyl and alkenyl groups may be optionally substituted; R" is selected from the group of hydrogen, F, Cl, Br, I, CF-3, CFzCl. CFjH, CFH?, OF;OJR'-'. CTWJR9, OR9, S(O)nR9, NR1 V1, Ci - C8 alkyl, C, - Cs haloalkyl. C, - Q heteroalkyi. C, - Cs cycloalkyl, aryl, arylalkyl, heteroaryl, C2 - Cs alkynyl and C?_ — Cs alkenyj. wherein the alkyl, haloalkyl, heteroalkyi, cycloalkyl aryl, arylalkyl, heteroaryl, alkynyi and alkenyl groups maybe optionally substituted; R' and R"4 each independently is selected from the group of hydrogen, OR-9, S(0),,Rl NR^R1 1 . C(Y)ORn, C(Y)NRloRn, C, - Cs alkyl, C, - C8 haloalkyl, C, -C8 heteroalkyi, C-, - Cs cycloalkyl, aryl, arylalkyl, heteroaryl, C.j - Cs alkynyl and C^ — Cg alkenyl, wherein the alkyl, haloalkyl, heteroalkyi, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups maybe optionally substituted; or R" and R"" taken together form a three to eight membered saturated or unsaturated carbocychc or heterocychc ring; or R" and R~' taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R' and R° taken together form a three to eight membered saturated or unsaturated carbocychc ring; or R"1 arid R1'5 taken together form a three to eight membered saturated or unsaturated heterocyclic ring; R.' and R6 each independently are selected from the group of hydrogen, CF3, CF--CL C:F2H, CFH2, C, - C8 alkyl, d - C8 haloalkyl, C, - Cg heteroalkyl, C3 - Cg cvcloaikyl, aryl, arylalkyl, heteroaryl, C2 - Cs alkynyl and C2 - Cg alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl. aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; or R"" and R° taken together form a three to eight membered saturated or unsaturated carbocychc ung; or R; and R'J taken together form a three to eight membered saturated or unsaturated heterocychc ring; or R!) and Rl j taken together form a three to eight membered saturated or unsaturated beterocydic ring; R' is selected from the group of hydrogen, F, Cl, Br, 1, C] - Cs alkyl, Ci - Cg haloalkyl, C, - Q heteroalkyl, aryl, heteroaryl, OR9, S(0),,R9, NR10R", C(Y)ORU and C(Y)NR10R', wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optional! v substituted; Rft is selected from the group of hydrogen, F, Cl, Br, I, C] - Cg alkyl. Ci - Cg haloalkyl, C, - C8 heteroalkyl, aryl, heteroaryl, OR9, S(0)nR9, NR10Rn, C(Y)ORU and C( Y')NR! 0R: ! , wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optional!v substituted; R" is selected from the group of hydrogen, Ci - Cg alkyi, C] - Cg haloalkyl, Q --- Q heteroalkvl, aryl, heteroaryl and arylalkyl, wherein the alkyl, haloalkyl. heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R1" K; selected from the group of hydrogen, Ci - Cg alkyl, C; - C8 haloalkyl, Q - C8 heteroalkvl, aryl. heteroaryl, arylalkyl, C02R12, C(0)R12, S02R12 and S(O)R12, wherein the alkyu haioalkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R' and R1" each independently is selected from the group of hydrogen, Ci - Cg alkyl, C - Cg lialoalkyi, Ci - Cg heteroalkyl, aryl, heteroaryl and arylalkyl, wherein the alkyl, haloalkyl, heteroalkyl. aryl, heteroaryl and arylalkyl groups may be optionally R'""' is selected from the group of Ci - Cs alkyl, C] - Cg haloalkyl, Q - Cg heteroalkyl, C- - Cs alkenyl. C2 - Cg alkynyl, C3 - Cg cycloalkyl, aryl, heteroaryl, arylalkyJ and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, ary], heteroaryl, arylalkyl and heteroarylalky] groups may be optionally substituted; R! o is selected from the group of hydrogen, d - Cg alkyl, Ci - Cg haloalkyl, Ci - Q heteroalkyl, COR17, CO2R17 and CONR12R17, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R1 ' is selected from the group of hydrogen, d - Cg alkyl, Q - Cg haloalkyl and C- C'a heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups maybe optionally substituted; Ri s is selected from the group of hydrogen, F, Br, CI, I, CN, d - Cg alkyl, Ci - C8 haloalkyj, C, - C8 heteroalkyl, OR16, NRI6R17, SR16, CH2R16, COR17, C02R17, C(3NRl t >R17, SOR17 and SO2R17, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R1" is selected from the group of hydrogen, Ci - Cg alkyl, Ci - Cg haloalkyl, Ci - Cs heteroalkyl, C2 - - Cg alkenyl, Ci - Cg alkynyl, C3 - Cg cycloalkyl, aryl, heteroaryl. arvlalkyl and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkvl, aryl, heteroaryl, arylalkyl and heteroarylalkyl groups may be optionally substituted; ra is selected from the group of 0, 1 and 2; n is selected from the group of 0, 1 and 2; V is selected from the group of O and S; W is selected from the group of O, S(O)n, NH, N{R13}, N{C(Y)RU} and NiSO2Ri : j : X arid Z each independently is selected from the group of O, S(O)n, NH, N{RU}, N > C( Y ) R : ; ! , N! SO2R12} and N{S(0)R12}; and is selected from the group of O, S, N{R19} and N{OR19]; and pharmaceutically acceptable salts thereof. Detailed Description of the Invention In accordance with the present invention, we have developed novel compounds, oppositions and methods of preparing non-steroidal compounds that are AR CI modulators. Specifically, we have developed agonists, partial agonists (i.e., partial activators and/or tissue-specific activators) and antagonists for androgen receptors and methods of preparing these compounds and compositions. Compounds of the present invention may be high affinity, high specificity agonists, partial agonists, or antagonists for androgen receptors. In accordance with the present invention and as used herein, the following structure definitions are provided for nomenclature purposes. Furthermore, in an effort to maintain consistency in the naming of compounds of similar structure but differing substituents, the compounds described herein are named according to the following general guidelines. The numbering system for the location of substituents on such compounds is also provided. A 2/;/-[l,4]oxazino[2,3-_/]qirinoline is represented by the following structure: 3 An 8//-[1,4]oxazino[2.3-/]quinoline is represented by the following structure: A 111, 6H-pyrrolo[l',2':4,5][l,4]oxazmo[2,3-f]quinolin-2-one is represented by the following; structure: In accordance with the present invention and as used herein, the following terms are defined with the following meanings, unless explicitly stated otherwise. The term "alkyl." alone or in combination, refers to an optionally substituted straight-chain or branched-chain alkyl radical having from 1 to about 12 carbon atoms. The term also includes substituted straight-chain or branched-chain alkyl radicals having from 1 to about 6 carbon atoms as well as those having from 1 to about 4 carbon atoms. Examples of alkyl radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-buty , tert-butyl. tert-ainyl, pentyl, hexyl, heptyl. octyl and the like. The ;erm "'alkenyl," alone or in combination, refers to an optionally substituted siraiglH-diam or branched-chain hydrocarbon radical having one or more carbon-carbon doubie-bonus and having from 2 to about IS carbon atoms. The term also includes substituted straight-chain or branched-chain alkyl radicals having one or more carboncarbon double bonds and having from 2 to about 6 carbon atoms as well as those having from 2 to about 4 carbon atoms. Examples of alkenyl radicals include ethenyl, propenyl. 1,4-butadienyl and the like. The term "alkynyl," alone or in combination, refers to an optionally substituted straight-chain or branched-chain hydrocarbon radical having one or more carbon-carbon triple-bonds and having from 2 to about 12 carbon atoms. The term also includes substituted straight-chain or branched-chain alkyl radicals having one or more carboncarbon tvripie bonds and having from 2 to about 6 carbon atoms as well as those having from 2 u> about 4 carbon atoms. Examples of alkynyl radicals include ethynyl, propynyl. buivnyl :ind die Irke. The term 'heteroalkyl" refers to alkyl groups, as described above, in which one or more skeletal atoms are oxygen, nitrogen, sulfur or combinations thereof. The term heteroalkyi also includes alkyl groups in which one 1 to about 6 skeletal atoms are oxygen, nitrogen, sulfur or combinations thereof, as well as those in which 1 to 4 skeletal atoms are oxygen, nitrogen, sulfur or combinations thereof and those in which 1 to 2 skeletal atoms are oxygen, nitrogen, sulfur or combinations thereof. The lerm "alkoxy." alone or in combination, refers to an alkyl ether radical wherein the term alkyl is defined as above. Examples of alkoxy radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like. The ienn "aryloxy," alone or in combination, refers to an aryl ether radical wherein the term aryl is defined as below. Examples of aryloxy radicals include phenoxy, berizyioxy and the like. The term "alkylthio," alone or in combination, refers to an alkyl thio radical wherein the lerrn alkyl is defined as above. The term 'arylthio," alone or in combination, refers to an aryl thio radical wherein the term aryl is defined as below. The ienn "oxo" refers to ~-0. The ienn "aryl," alone or in combination, refers to an optionally substituted aromatic run; system. The term aryl includes monocyclic aromatic rings, polyaromatic rings ami poiycyclic aromatic ring systems containing from six to about twenty carbon atoms. The lerrn aryl also includes monocyclic aromatic rings, polyaromatic rings and poiycyclic nag systems containing from 6 to about 12 carbon atoms, as well as those containing from 6 to about 10 carbon atoms. The polyaromatic and poiycyclic aromatic rings systems may contain from two to four rings. Examples of aryl groups include, without 'limitation, phenyl, biphenyl, naphthyl and anthryl ring systems. The term "heteroaryl" refers to optionally substituted aromatic nng systems containing from about five to about 20 skeletal ring atoms and having one or more heteroatoms such as, for example, oxygen, nitrogen and sulfur. The term heteroaryl also includes optionally substituted aromatic ring systems having from 5 to about 12 skeletal ring atoms, as well as those having from 5 to about 10 skeletal ring atoms. The term heteroaryl may include five- or six-membered heterocyclic rings, poiycyclic heteroarornadc ring systems and polyheteroaromatic ring systems where the ring system has tvvc, three or four rings. The terms heterocyclic, poiycyclic heteroaromatic and polyheteroaromatic include ring systems containing optionally substituted heteroaromatic rings having more than one heteroatom as described above (e.g., a six membered ring with two nitrogens), including-polyheterocyclic ring systems of from two to four rings. The' term heteroaryl includes ring systems such as, for example, furanyl, benzofuranyl, chromenyl pyndyl pyrrolyl, mdolyl, quinolinyl, N-alkyl pyrrolyl. pyridyl-N-oxide, pynmidovl, pyrazmyl, imidazolyl, pyrazolyl, oxazolyl, benzothiophenyl, purinyl, indolizinyi, Lhienyl and the like. The term "heteroarylalkyl" refers to a Ci-C4 alkyl group containing a heteroaryl group, each of which may be optionally substituted. The term "heteroarylthio" refers to the group -S-heteroaryl. The term "acyloxy" refers to the ester group ~OC(O)-R, where R is hydrogen, alkyl, alkenyl, alkynyl, aryl, or arylalkyl, wherein the alkyl, alkenyl, alkynyl and arylalkyl groups may be optionally substituted. The term "carboxy esters" refers to -C(O)OR where R is alkyl, aryl or arylalkyl, wherein the alkyl, aryl and arylalkyl groups may be optionally substituted. The ierrn 'carboxamido" refers to (Figure Removed) where R and R' each independently is selected from the group of hydrogen, alkyl, aryl and arylalkyl, wherein the alkyl, aryl and arylalkyl groups may be optionally substituted. The icrrn "cycloalkyl", alone or in combination, refers to a monocyclic, bicyclic or tricyclic alkyl radical wherein each cyclic moiety has from 3 to about 8 carbon atoms. Examples oj'cycloalkyl radicals include cyclopropy], cyclobutyl, cyclopentyl, cyclohexyl and the like. The term "arylalkyl." alone or in combination, refers to an alkyl radical as defined above in which one hydrogen atom is replaced by an aryl radical as defined above, such as, for example, benzyl, 2-phenylethyl and the like. The lenns haloallcyl, haloalkenyl, haloalkynyl and haloalkoxy include alkyl, aikenyl, alkynyl and alkoxy structures, as described above, that are substituted with one or more fluorines, chlorines, bromines or iodines, or with combinations thereof. The lenns cycloalkyl, aryl, arylalkyl, heteroaryl, alkyl, alkynyl. alkenyl, haloalkyl and heteroalkyl include optionally substituted cycloalkyl, aryl, arylalkyl, heteroaryl, alkyl, alkynyl, alkeriyl, haloalkyl and heteroalkyl groups. . The term "carbocycle" includes optionally substituted, saturated or unsaturated, three- to eight-mernbered cyclic structures in which all of the skeletal atoms are carbon. The term "heterocycle" includes optionally substituted, saturated or unsaturated. three- to eighr-membered cyclic structures in wloich one or more skeletal atoms is oxygen, nitrogen, sulfur, or combinations thereof. The term "acyl" includes alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl substituents attached to a compound via a carbonyl functionality (e.g., -CO-alkyl, -COarvl, -CO-arylalky! or -CO-heteroarylalkyl, etc.). "Optionally substituted" groups may be substituted or unsubstituted. The substituents of an "optionally substituted" group may include, without limitation, one or more substituents independently selected from the following groups or designated subsets thereof alleys, alkenyl, alkynyl, heteroalkyl, haloalkyl, haloalkenyl, haloalkynyl, cycioalkyl, aryl. heteroaryl, arylalkyl, heteroarylalkyl, alkoxy, aryloxy, haloalkoxy, armno, alkylammo, dialkylamino, alleyIthio. arylthio, hetero arylthio, oxo, carboxyesters, carboxuumlo acyloxy, hydrogen. F, Cl, Br, I, CM, NO2, NH2, N3, NHCH3, N(CH3)2, SH, SCTh. OH, OCH.,, OCF3, CH3, CF3, C(O)CH3? CO2CH3. C02H, C(O)NH:, OR9, SR9 and NJV'R1 \ An optionally substituted group may be unsubstituted (e.g., -CBbCHj), fully .substituted (e.g.. -CF:.CF3), monosubstituted (e.g., -CHaCHoF) or substituted at a level anywhere in-between fully substituted and monosubstututed (e.g., -CHjCFV). The term "halogen" includes F, CI, Br and I. The term "mediate" means affect or influence. Thus, for example, conditions mediated by an androgen receptor are those in which an androgen receptor plays a role. Amlrogen receptors are known to play a role in conditions including, for example, acne, male-pattern baldness, sexual dysfunction, impotence, wasting diseases, hirsutism, hypogonadism, prostatic hyperplasia, osteoporosis, cancer cachexia, and hormonedependent cancers. The term "selective" refers to compounds that display reactivity towards a particular receptor (e.g., an androgen receptor) without displaying cross-reactivity towards another receptor (e.g., glucocorticoid receptor). Thus, for example, selective compounds of the present invention may display reactivity towards androgen receptors without displaying cross-reactivity towards glucocorticoid receptors. Compounds of the present invention are represented by those having the formula: (Figure Removed) wherein: R: is selected from the gi-oup of hydrogen, F, Cl, Br, I, NO2, OR9, NR10R!1, S(0)nR9. C, C8 alkyl, Q - C8 haloalkyl, Ci - Cg heteroalkyl, C3 - CR cycloalkyl, aryl, arylalkyl, heteroaryl, C2 - Cg alkynyl and C2 - Cg alkenyi, wherein the alkyl, haloalkyl, heteioalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyi groups maybe optionally substituted; R- is selected from the group of hydrogen, F, CL Br, I, CF3, CF2CL CF2H, CFH2, CF3OR\ (JH;OR°, OR9, S(OjnR9, NR10R", C, - C8 alkyl, C, - C8 haloallcyl, C, - Cg heteroalkyl, (.% - Cx cycloalkyl, aryl, arylalkyl, heteroaryl, C2 - Cg alkynyl and C2 - Cg alkenyi. wheri.'in the alkyl, haloalkyl, heteroalkyl, cycloalkyl aryl. arylalkyl, heteroaryl, alkynyl and aikenyl groups may be optionally substituted; R"' and R'! each independently is selected from the group of hydrogen, OR9, SiOlnR". MR^'R1 ! , C(Y)OR!I, CfY)NRluR! I , C, - Cs alkyl, Ci - Cs haloalkyl, Ci - Cs heteroalkyl, (.;, Cg cycloalkyl, aryl. arylalkyl, heteroaryl, C2 — Cs alkynyl and C2 - Cg alkenyi wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and aikenyl groups may be optionally substituted; or R' and R taken together form a three to eight membered saturated or unsaturated carbocyclic or heterocyclic ring; or R ' and R~' taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R"; and R° taken together form a three to eight membered saturated or unsaturated yclic ring; or R" and R'"' taken together form a three to eight membered saturated or unsaturated Rs and R() each independently are selected from the group of hydrogen, CF3; CF2C1, CF2H, CFH2, Ci - C8 alkyl, C, - C8 haloalkyl, C,- Cg heteroalkyl, C3 - Cs cycloalkyl, aryi, arylalkyl, heteroaryl, C2 - Cs alkynyl and €2 - Cg alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl. alkynyl and alkenyl groups may he optionally substituted; or R:~ and R6 taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R"' and R.'J taken together fonn a three to eight membered saturated or unsaturated heterocyclic 'tg: or Rb and R.1" taken together fonn a three to eight membered saturated or unsaturated heterocychc ring; R' is selected from the group of hydrogen, F, Cl, Br, I, Ci - Cg alky], C] - Cg haloalkyl, C - Cs heteroalkyl, aryl, heteroaryl, OR9, S(0)nR9, NR.'°R", C(Y)ORn and C( V)NR' J R ' ' , wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optionally substituted; R' is selected from the group of hydrogen. F, Cl, Br, 1, Ci - Cg alkyl, Ci - Cg haloalkyl, (" - C« heteroalkyl, aryl, heteroaryl, OR9, S(O)nR9, NR10RU, C(Y)ORU and ( i N r l \ ; ( ) R ' ! , wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optionally substituted; R' is selected from the group of hydrogen, Cj - Cg alkyl, Cj - Cs haloalkyl, Ci - (I'* heteroalkyl, aryl, heteroaryl and arylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups maybe optionally substituted; Rl ( ) is selected from the group of hydrogen, Q - Cs alkyl, Q - Cg haloalkyl, C\ - Cg heteroalkyl, aryl, heteroaryl, arylalkyl, CO2R12, C(O)R12, SO2R12 and S(O)R12, wherein the alkyl, haloaJkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R 1 ' and R'" each independently is selected from the group of hydrogen, Ci — Cg alkyl. Ci - C;; haloalkyl. C] - Cg heteroalkyl, aryl, heteroaryl and arylalkyl, wherein the alkyl. haioalkyl. heteroalkyk aryl, heteroaryl and arylalkyl groups may be optionally substituted; R! j is selected from the group of Ci - Cg alkyl, Q - Cg haloalkyl. Ci - Cs heteroalkyk C2 Cg alkenyl, C? - Cg alkynyl, Cs - C8 cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherem the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl groups may be optionally substituted; R'6 is selected from the group of hydrogen, C\ - Cs alkyl, d - Cg haloalkyl, Q - C,; heteroa!k\'l, COR17. CO:R17 and CONR12R17, wherem the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R' us selected from the group of hydrogen, d - C§ alkyl, Ci - Cg haloalkyl and C - CR heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups maybe optionally substituted; R18 is selected from the group of hydrogen, F, Br, Cl, I, CN, d - C8 alkyl, C, - C8 haloalkyl, d - C8 heteroalkyl, OR16, NR16R17, SR16, CH2R16, COR17, CO2R17, CONRH'R! , SOR.1' and SO2R17, wherein the alkyl, haloallcyl and heteroalkyl groups may be optionally substituted; R.; y is selected from the group of hydrogen, Ci - Cg alkyl, d — Cs haloalkyl, d - d; heteroalkvl. d - Cg alkenyl, d - Cg alkynyl, d - Cg cycloalkyl, aryl, heteroaryl, aryialky! and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycJoalkyl, aryl, heteroaryl. arylalkyl and heteroarylalkyl groups may be optionally substituted; m is selected from, the group of 0. 1 and 2; ii is selected from the group of 0, 1 and 2; V is selected from the group of O and S; VV is selected from the group of O, S(O)n, NH, N{R13}, N{C(Y)RU) and N!SO?RMi ; X ana Z each independently is selected from the group of 0, S(O)n, Nil, N{Rn}, V is selected from the group of O, S, N{R19} and N{OR19}; and pharmaceutically acceptable salts thereof. in one aspect, the present, the invention provides compounds represented by formula I through IV. fn another aspect, the present invention provides a pharmaceutical composition comprising an effective amount of an AJR. modulating compound of formula I through IV shown above, wherein R! through Rlj. R'° through R!9. m, n, V, W. X, Y, and Z are as described above. In another aspect, the present invention provides a method of modulating processes mediated by ARs by administering to a patient an.effective amount of a compound .of formula I through IV shown above, wherein R! through R13, R16 through R19, m. n, V, W, X, Y'", and Z are as descnbed above. In one aspect, the modulation is activation, while in another aspect, the modulation is inhibition. In each case, the method involves administering to a patient a pharmaceutically effective amount of a compound of formula I through IV shown above, wherein R1 through R13, R16 through R19, m, n, V, W, X, Y, and Z are as described above. With regard to the foregoing variables, the inventors contemplate any combination of the Markusb groups as set forth above and as described in the following table. (Table Removed) The compounds of the present invention can be synthesized as pharmaceutically acceptable salts for incorporation into various pharmaceutical compositions. As used herein, phannaceutically acceptable salts include, but are not limited to. hydrochloric, hydrobromic, hydroiodic, hydrofluoric, sulfuric, citric, maleic, acetic, lactic, mcotmic, succmic, oxalic, phosphoric, malonic, salicylic, phenylacetic, stearic, pyndine, ammonium, piperazme, diethylamine, mcotmamide, formic, urea, sodium, potassium, calcium, magnesium, zinc, lithium, cmnamic, methylammo, methanesulfonic, picric, tartaric. tnethylaniino, dimethyl ammo, tris(hydroxymethyl)ammomethane and the like and suitable combinations of any two or more thereof. Additional phannaceutically acceptable salts are known to those skilled in the art.. AR agonist, partial agonist and antagonist compounds (including compounds with tissue-selective AR modulator activity) of the present invention may be useful in the treatment of process(es) mediated by androgen receptor(s), including acne (antagonist), male-pattern baldness (antagonist), male hormone replacement therapy (agonist), sexual dysfunction t agonist), wasting diseases (agonist), hirsutism (antagonist), stimulation of hematopoiests (agonist), hypogonadism (agonist), prostatic hyperplasia (antagonist), osteoporosis (agonist), male contraception (agonist), impotence (agonist), cancer cachexia (agonist), various hormone-dependent cancers (e.g., prostate cancer (antagonist), breast cancer and the like), process(es) requiring anabolic agents (agonist) and the like. It is understood by those of skill in the art that a partial agonist may be used where agonist activity is desired, or where antagonist activity is desired, depending upon the AR modulator profile of the particular partial agonist. h is understood by those skilled in the art that while the compounds of the present invention will typically be employed as selective agonists, partial agonists or antagonists, that there may be instances where a compound with a mixed steroid receptor profile is desirable. For example, use of a PR agonist (z.e.,..progestin) in female contraception often leads to the undesired effects of increased water retention and acne flare-ups, hi this instance, a compound that is primarily a PR agonist, but also displays some AR and MR modulating activity, may prove useful. Specifically, the mixed MR effects would be useful to control water balance in the body, while the AR effects would help to control any acne flare-ups that occur. Furthermore, it is understood by those skilled in the art that the compounds of the present invention, including pharmaceutical compositions and formulations containing these compounds, can be used in a wide variety of combination therapies to treat the conditions and diseases described above. Thus, the compounds of the present invention can be used in combination with other hormones and other therapies, including, without limitation, chemotherapeutic agents such as cytostatic and cytotoxic agents, immunological modifiers such as interferons, interleukins, growth hormones and other cytokmes, hormone therapies, surgery and radiation therapy. Representative AR modulator compounds (i.e., agonists and antagonists) according 10 ihe present invention include: (3^?)-2.3.4,7-Tetraliydro-3-methyl-10-(trifluoromethyl)- •S//-J i ,4ioxazmoj 2,3-/]qumolin-8-one (Compound 101); (3^?)-2,3,4,7-Tetraliydro-3,4- dimethy!" i '">-( '.n!luoromethyl)-8//-[l,4]oxazino[2,3-/]qu.inolin-8-one (Compound 102); i3A'}-4-Ethyl-2.3,4.7-tetrahydro-3-metliyl-10-(trifluoromethyl)-8^f"-[l,4]oxazino[2.3- _/]qumolin-S-one (Compound 103); (3^)-2,3,4,7-Tetrahydro-3-methyl-4-(2,2,2- tnflnoroethyr)'-l()-(tritluoromethyI)-8Jfir-[l,4]oxazino[2,3-/]quinolin-8-one (Compound 104); (3A>i-2,3,4.7-Tetrahydro-3-methyl-4-propyl-10-(trifluoromethyl)-8J:7'- [l,4]oxazino[2.3-/]qumolin-8-one (Compound 105); (3£)-4-Allyl-2,3,4,7-tetrahydro-3- meihyl-lO-(tritluoromethyl)-8J:f-[l,4]oxazino[2,3-/lquinolin-8-one (Compound 106); (3^?)- 3-.i£thyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8fl"-[l,4]oxazmo[2,3-/]qumolin-S-one t Compound 107): (3^)-3-Ethyl-2,3,4,7-tetraliydro-4-methyl-l0-(trifluoromethyl)-8/7- I 1,4]oxazmo[2,3:/]qumolrn-8-one (Compound 108); (3J?)-3,4-Diethyl-2,3,4,7-tetrahydro- 1 0-(mnuoromethy])-8/J-[l,4]oxazino[2,3-/]qumolin-8-one (Compound 109); (3^)-3- E thy 1-2,3,4,7- ietrahydro-4-(2,2,2-tnfluoroethyl)-10-(trifluoromethyl)-8//- j 1.4]oxazino[2,3-/]quinolm-8-one (Compound 110); (3^?)-4-(2-Chloro-2,2-difluoroethyl)- 3-ethyl-2.3,4,7-tetrahydro-10-(trifluoromethyl)-8/7-[l,4]oxazmo[2,3-/|quinolin-S-one (Compound 111); (3jR)-4-(2,2-Difluoroethyl)-3-ethyl-2?3,4,7-tetrahydro-10- (tnfluoromethyl)-S^-[l,4]oxazino[2,3:/]quinolin-S-one (Compound 112); (3J?)-3-Ethyl- 2,3,4)7-tetrahydro-4-propyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-/]quinolin-8-one (Compound 113); (3^)-4-Allyl-3-ethyl-2,3;4..7-tetrahydro-10-(tnfluoromethyl)-8f/- [1.4]oxazino[2,3-f)quinolm-8-one (Compound 114); (3^)-3-Ethyl-2,3,,4,7-tetrahydro-4- isobu(yl-10-(trifluoromethyl)-8//'-fl;4]oxazino[2,3-/]quinolin-8-one (Compound 115); (37?/5)-2,3,4.'^-'J etrahydro-3-propyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2?3-_/]quinolm- 8-one (Compound 116); (3/^/5)-2,3:,4,7-Tetrahydro-4-methyl-3-propyHO- (tnfluoromethyl)-S//-[l,4]oxazino[2,3-/lquinolm-S-one (Compound 117); (3^/S)-4-Ethyl- 2,3,4,7-tetrahvdro-3-propyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8F- [1,4]oxazino| 2.3:/]quinolin-8-one (Compound 118); (3/?/S)-2,3,4,7-Tetrahydro-3-propyl- 4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8f/-[l,4]oxazino[2,3-_/]quinolin-8-one (Compound 119); (3^)-2,3,4J-Tetrahydro-3-isopropyl-10-(trifluoromethyl)-8/f- "1,4joxazmo| 2,3-/]quinolm-8-one (Compound 120); (3J?)-2,3,4,7-Tetrahydro-3-isopropyl- 4-methyl-lO-itn.fluoromethyl)-S//:-[l,4]oxazmo[2,3-/]quinolin-8-one (Compound 121); (3^)-4-iilhyl---2.3,4,7-tetraliydro-3-isopropyl-10-(trifliioromethyl)-S/i-[L4]oxazino[2,3- ./]quinolin-S-c>ne (Compoimd 122), (3/?)-2!3,4J7-Tetrahydro-3-isopropyi-4-(2,2r2- tntluoroethyJ)--10-(trifluoromethyl)-87:/-[ l,4]oxazmo[2,3-/]qumolm-8-one (Compound 123); (3/?)-4-i2-Chloro-2,2-difluoroethyl)-2,3]4r7-tetrahydro-3-isopropyl-lO- (trrnuoromethy])-8/i-[ 1,4]oxazino[2,3-/lquinolin-8-one (Compound 124); (37J)-4-(2,2- Difluoroech.yi)-2,3,4.7-tetraliydro-3-isopropyl-10-(trifluoromethyl)-8_ftr-[l,4]oxazino[2,3- /lqumolin-8-rme (Compound 125); (37?)-4-Allyl-2,3,4,7-tetraliydro-3-isopropyl-10- (trinuornmetl!ylV8/f-[l ;4]oxazmo[2,3-/)quinolin-8-one (Compound 126); (37?)-2,3,4,7- Tetrahydro-3 phenyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-/]quiiiolin-8-on.e (Compound 127); (3^)-2.3.4,7-Tetrahydro-3-phenyl-4-(2,2;2-trifluoroethyl)-10- ('iriiluoromethyr}-SjY-[l,4]oxazmo[2,3-/]qmnolin-8-one (Compound 128); (3J?j-4- Cyciopropylmethyi-2,3,4,7-tetrahydro-3-phenyl-10-(tnfluoromethyl)-8//- [L4]oxazmo[ 2,3:/]quinolm-8-one (Compound 129); (3J?)-3-Benzyl-253,4,7-tetrahydro-4- (2.2,2-trifluoroethyl)-10-('trifluoromethyl)-8//'-[l,4]oxa2ino[2,3-/]quinolin-8-one (Compound 130); 2,3,4,7-Tetrahydro-10-(trifluoromethyl)-8/:f-[l,4]oxazino[2,3- /Iqumolin-S-one (Compound 131); 2,3.4,7-tetrahydro-4-(2.2.2-trifluoroethyl)-10- (tri.fliioromethy1,)-8Ar-[l,4]oxazino[2,3-/]quinolin-8-one (Compound 132); (7a 7,7a.S.9:l 0,1 Oa-Hexahydro-l-(tnfluoromethyl)-7-(2,2,2-trifluoroethyl)-4Fcyclopenta ::.,6][l,4joxazino[2,3:/]qumolin-3-one.(Compound 133); (7aR,10ai5)-7-Ethyl- 7,7a,8,9,10,! Oa-hexahydro-l-(trifluoromethyl)-4//-cyclopenta[5,6][l,4]oxazino[2,3- ;]quinolin-3 -one (Compound 134); (7aJ?,10a1S)-7,7a,8,9,10,lOa-Hexahydro-3-isopropoxy- 1-(triflLioroniethylV7-(2.2,2-trifluoroethyl)-4J?:r-cyclopenta[5,6][l.,4]oxazmo[2,3- /Iqumolin 3 -one (Compound 135); (i)-(21S1,3^)-2,3,4,7-Tetraliydro-2,3-dimethy]-4-(2,2,2- trifluoroethyl)-10-(trifluorornethyl)-8/:/-[l,4]oxazino[2,3-/]qiiinolm-S-orie (Compound 136); (7/0-6,6a,7,S,9,10-Hexahydro-4-(trifluoromethyl)-l//- pyT.ro]o[ 1 '.2':4,5][1.4]oxazmo[2,3-/]quinolin-2-one (Compound 137); 2,3,4,7-Tetrahydro- 2,2.4-trimethyl-10-(trifluororaethyl)-8//'-[l34]oxazino[2,3-/lquinolin-8-one (Compound 138); (3/?)-S-Ch]oro-3-ethyl-3,4-dihydro-8-isopropoxy-4-(2,2,2-trifluoi-oetliyl)-10- (hifluoi-omei.hy])-2/f-[l?4]oxazino[2,3-/|quinoline (Compound 139); (3R) -3-Ethyl-3,4- diliydro-S-isopropoxY-8-methoxy-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-2^- [ 1,4]oxa:^no[2.3:/]quinolme (Compound 140); (±)-2,3?4..7-Tetrahydro-4-(2,2,2- triiluoroethy]')- ?,]0-bis(trifIuoromethyl)-8/jr-[l,4]oxazino[2,3-/]quinolin-S-one (Compound 141); (-)-2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10- his(inflLiorovnethyl)-8Jif-[ l,4]oxazino[2,3-/]quinolin-8-one (Compound 142); (-t-)-2.,3,4,7- Teu'ahyi'iro---i-(-!,2.2-trifluoroethyi)-3,lU-bis(trifIuoromethyl)-S/;r-[l,4]oxazino[2,3- /lquinolin-8-on Within such group, representative compounds include: 3j?)-2.3,4.7-Tetrahydro-3- rnethyl-4-(2.2,2-trifluoroethy])-10-(trilluoromethyl)-8/f-[l,4]oxazino[2,3-/]qumolm-8-one (,r:ompound 104); (3/?)-3-Ethyl-2.3,4,7-tetrahydro-4-(2,2,2-trifluoroethyl)-10- (trifluoromeUiiyl)-8//-[l,4]oxazino[2J3-/]qiiinolin-S-one (Compound 110), (37?)-4-(2- Chloro-2,2-difluoroethyl)-3-ethyI-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8//- [L4]oxazino[2,3-_/]quinolin-8-one (Compound 111); (3JR)-4-(2,2-Difluoroethyl)-3-ethyl- 2.3.4,7-tetrahydro-10-(trifluoromethyl)-87/-[l,4]oxazino[2,3-/|quinolin-8-one (Compound 112): (37\)-2,3,4,7-Teti-ahydro-3-isopropyl-4-(2,2,2-trifluoroethyl)-lO-(trifluoromethyl)- 8^'-.i ,4]oxar'jno[2,3-/lquinolin-8-one (Compomid 123); (3J?)-4-(2-Chloro-2,2- difluoroethyl)-2,3,4,7-tetrahydro-3-isopropyl-10-(trifluoromethyl)-8/ir-[l,4]oxazino[2.3- jquinolin-8-one (Compound 124); (3^)-4-(2,2-DifluoroethyI)-2,334,7-tetrahydro-3- isopropyl-10••(tnfluoromethyl)-8/-/-[l,4jOxazino[2,3-/jquinolin-8-one (Compound 125); l'7a/e. IOa,ST.)-T-Efhyl-".7a,S,9,10,1 Oa-hexahydro-1 -(tnfluoromethyl)-4//- cyclopenta[5,6]f l,4]oxazino[2,3-_/]qumolin-3-one (Compound 134); (7a/?,10a,S)- 7,7a,S,9.JOJ10a-Hexahydro-l-(trifluoromethyl)-7-(2.2,2-trifluoroethyl)-4J:?'- cyclopenta[5.6][ l,4]oxazino[2,3-/]qmnolin-3-one (Compound 133); (±)-(25',3^)-2;3,4,7- l-etrahvdro-2,3-dm-iethyl-4-(2,2,2-trifluoroethyl)-10-(tnfLuoromethyl)-8/i- [ 1,4joxii2ino|2,3~/]qmnolin-8-one (Compound 136); (±)-2,3,4,7-Tetrahydro-4-(2,2.2- tnfluoroethy'0-3,10-bis(trifluoromethyl)-8/f-[l,4]oxazino[2,3-/lquinolin-8-one (Compound 141 j; (-)-2,3-4,7-TetTahydxo-4-(2,2,2-trifluoroethyl)-3;10- bis(trifluoroiiiethyl)-8//-[l,4]oxazino[2,3-/]quinolin-S-one (Compound 142); (+)-2,3,4,7- Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10-bis(trifluoromethyl)-8^r-[l,4]oxazino[2,3- _/]qumolin-S-one (Compound 143); (±)-2J3,4,7-Tetrahydro-3-(2J2,2-trifluoroethyl)-l0- (tnfluoromethyl)-8/:/-[l,4]oxazmo[2,3-f|quinolm-8-one (Compound 144); (±)-2,3,4,7- Tetrahydro-4-methyl-3-(2,2,2-trifluoroethyl)-10-(trifluoromeaiyl)-S^-[l,4]oxazino[2,3- /]quinolin-8-one (Compound 145); (±)-4-Ethyl-2,3,4,7-tetrahydro-3-(2,2,2-trifluoroethyl)- 1 ()-(frinuoromethyl)-8//-[l,4]oxazino[23-/jquinolin-8-one (Compound 146); (±)-2,3,4,7- Tetrahydro-3,4~bis(2,2,2-tnfluoroethylV 10-(trifluoromethyl)-8//-[l ,4]oxazmo[2,3- /lqi.iinolin-8-one (Compound 147); (-)-2,3,4,7-Tetraliydro-3,4-bis(2,2,2-trifluoroethyl)-10- (triiluoromethyl)-8^r-[l,4]oxazino[2,3-/jquinolin-8-one (Compound 148); (+)-2,3,4,7- TcinhydrC'-3,4-bis(2,2,2-trifluoroetliyl)-10-(trifluoromethyl)-Sjt/'-[l,4]oxazmo[2:3- /]qumolin-8-one (Compound 149); (±)-4-Cyclopropylmethyl-2,3,4.7-tetraliydro-3-(2.2,2- trifluor(iethyi)-lU-(tnfluoromethyI)-8//'-|"l34]oxazino[2,3-/lqumolin-8-one (Compound 150); (.3/0-4-Cyciopropylmethyl-3-ethyl-2,3.4,7-teti-ahydro-10-(trif]uoromethyl)-8Ar- [ 1Aloxozinoi 2,3:/lqumolm-8-one (Compound 151); (3JR)-4-(2-Chloroethyl)-2,3,4,7- totral]ydro-3-isopz-opyl-10-(trifluoroinethyl)-S//'-[l,4]oxazino[2,3-/lquinolm-8-one (Compound 1.52); (±)-2,3,4,7-Tetrahydro-2-methyl-4-(2,2,2-trifluoroethyl)-l 0- (iri iluoromethy! )-SH-[1,4]oxazmo[2,3-/]qumolm-S-one (Compound 153); (3/?)-3-Ethyl-4- (2-hydroxy-2-metbylpropyl)-2,3,4!7-tetrahydro-10-(trifluoromethyl)-8//-[l,4]oxazmo[2,3- y'JqmnoJin-S-one (Compound 154); (3^)-2,3,4;7-Tetrahydro-3-isobutyl-4-(2,2,2- mfluoroethy])-10-(tnfluoromethyl)-8//-[ 1,4]oxazmo[2,3-/lquinolm-S-one (Compound 155). Compounds of the present invention, comprising classes of heterocyclic nitrogen compounds and their derivatives, can be obtained by routine chemical synthesis, e.g., by modification of the heterocyclic nitrogen compounds disclosed or by a total synthesis approach. The sequences of steps for several general schemes to synthesize the compounds of 1 ^ the present invention are shown below. In each of the schemes the R groups (e.g., R , R", etc.) correspond to the specific substitution patterns noted in the Examples. However, it will be understood by those skilled in the art that other functionalities disclosed herein at the indicated positions of compounds of formulas I thorough IV also comprise potential substituents ibr the analogous positions on the structures within the schemes. Scheme I (Figure Removed) A synthesis of an 87^-[l,4]oxazino[2,3-/]quinolin-8-one compound (e.g., structures 9 and 11.), is depicted in Schemes I and II. The process of Scheme I begins with the Rnorr cyclization of a phenylenediamine denvative. for example, 5-chloro-l,3- phenylenediaraine (structure 1), with a p-ketoester. or its corresponding hydrate or hemiacetal, for example ethyl 4,4,4-triiluoroacetoacetate, to afford the corresponding (l//)-quinolin-2-one. See G, Jones, Comprehensive Heterocyclic Chemisny, Katritzky, A. R.; Rees, C. W., eds. Pergamon, New York, 1984. Vol. 2, chap. 2.08, pp 421-426, the disclosure of which is herein incorporated by reference. Reduction of the halide group could be achieved by chemical reduction, with, for example, a metal catalyst for example, 10% Pd-C. in a hydrogen atmosphere, to afford a compound of structure 2. Conversion of the aniline to a phenol could be effected by treatment of structure 2 with a diazotizmg agent, for example, sodium nitrite in sulfuric acid, to afford a compound of structure 3. Bromination of the phenol with a bromxnatmg reagent, for example. /V-brornosuccinimide, in the presence of a base, for example, diisopropylamine, affords a compound of structure 4. See S, Fujisaki, et. ai, Bull. Chem. Soc. Jpn. 1993, 66, 1576-1579, the disclosure of which is herein incorporated by reference. Selective protection of the phenolic oxygen could be achieved by treatment of structure 4 with an allcyl halide, for example, benzyl bromide, in the presence of a base, for example, :.esmm fluoride, to afford the corresponding ether. Protection of the pyndonc ring, with, for example isopropyl iodide, mediated by a base, for example, cesium fluoride, affords the corresponding imino ether (structure 5). Selective hydrolysis of the phenolic ether could be accomplished by acidic hydrolysis, with, for example, a 1:1 mixture of metbnnesulfonic acid and acetic acid, to afford a phenol of structure 6. (Figure Removed) T'he io] lowing transformations are illustrated in Scheme II. Alkylation of the phenolic oxygen was accomplished by treatment of the phenol with a protected amino alcohol, tor example, (J/?)-A-/-boc-almol, under Mitsunobu conditions, for example, tnphenylphosphine and diisopropyl azodicarboxylate, in the presence of a base, for example, ;V-methylrnorpholine, to afford the con-esponding Mitsunobu product. Removal of the r-butoxycarbonyl protecting group can be accomplished by acidic hydrolysis, with, for example, triiluoroacetic acid, to afford a compound of structure 7 (Scheme II). Closure of the amine to the aromatic halide can be achieved by treatment of compound with a transition metal for example Pd2(dba)3 in the presence of a ligand, for example, BINAP, and a base, for example, sodium /-butoxide, to afford a compound of structure 8. See S. Wagaw, et. al, J. Am. Chem. Soc. 1997, 119, 8451-8458, the disclosure of which is herein incorporated by reference. Treatment of a compound of structure 8 with an acid, for example hydrochloric acid in acetic acid, at elevated temperatures, affords an &H- [ 1.4Jox.azino| 2,3-/]quinolin-8-one of structure 9. Alternatively, treatment of a compound of structure 8 with an aldehyde or its corresponding hydrate or hemiacetal, for example, tniluoroacetaldehyde hemiacetal, m the presence of a reducing agent, for example, sodium cvanoborohydnde, in a carboxyhc acid, for example, trifluoroacetic acid, affords a compound of structure 10. Alternatively, alkylation could be achieve by alkylation of structure 8 with an alkyl halide, for example, allyl bromide, mediated by a base, for example potassium carbonate, to afford a compound of structure 10. Treatment of a compound of structure 10 with an acid, for example hydrochloric acid in acetic acid, affords an o/i'-[l ,4]oxazmo|2,3-/Jqumolin-8-one, a compound of structure 11. Alternatively, treatment of a compound of structure 9 with an aldehyde or its corresponding hydrate or hemiacetal, for example, cyclopropylmethylcarboxaldehyde, in the presence, of a reducing agent, for example, sodium cyanoborohydnde, in a carboxylic acid, for example, acetic acid, affords a compound of structure 11. An enaniiorner of structures 9 or 11, or a racemic mixture may be obtained by the synthetic route as described in Scheme II, by starting with the enantiomer of the /?- aminoalcohoi as shown (e.g., an (iT)-/?-ammo alcohol), or a racemic mixture of the ftammoalcohoi shown (e.g., a (+)-/?-amino alcohol. Accordingly, an ( employed in Scheme II, produces an (iSVquinolinone; an (J?)-/?-amino alcohol, employed m Scheme I I . produces an (/f)-quinolinone; and a racemic mixture of the /?-amino alcohol, employed in Scheme II, produces a racemic mixture of the corresponding quinolinone. A racemic mixture of quinolinones could be separated into its corresponding enantiomers by separation on chiral HPLC with, for example, a chirapak AS column eluted with hex.anes:ethanol. Scheme [II (Figure Removed) The asymmetric synthesis in Scheme III begins with the chemo- and regioselective A'-alkylation of a |3-ammoalcohoi, either as a single enantiomer (R or tS) or its racernate. for example. (Sj-prolinol, onto a 3,4-dihalonitrobenzene, for example, 3,4- difiuoromtrolienzene, mediated by abase, for example, sodium bicarbonate, to afford an optically pure arylamino alcohol (e.g., structure 14). Benzoxazine compounds (e.g., structure 15'). may then be formed by cyclization of the A'- alky 1 substituted ammo alcohol compounds (.;.;., structure 14) by treatment with a base such as sodium hydride. Reduction o t ' n i t r o benzoxazme compounds (e.g., structure 15) with a reducing agent, for example, zinc, and calcium chloride affords an amino benzoxazme compound (e.g.. structure 16) Treatment of an ammo benzoxazme with a j3-ketoester or its corresponding hydrate, tor example ethyl 4,4,4-trifluoroacetoacetate, at elevated temperatures, affords the corresponding acetanilide. Treatment of the acetanilide with an acid, for example, sulfuric acid, affords an optically pure quinolinone compound (e.g., structures 17 and 18). An enantiomer of structure 17, or a racemic mixture maybe obtained by the synthetic route as described in Scheme III, by starting with the enantiomer of the /?-aminoalcohol as shown (e.g., an uS>/>-amino alcohol), or a racemic mixture of the /?-aminoalcohol shown (e.g., a (±)-/Aamino alcohol. Accordingly, an (S)-/3-amino alcohol, employed in Scheme III, produces an i6T)-quinolinone; an (/?)-/?- amino alcohol, employed in Scheme III, produces an (A')-quirioiinone; and a racernic mixture of the /?-amino alcohol, employed in Scheme III, produces a racemic mixture of the corresponding quinolinone. Scheme IV A synthesis of an 8Ar-[l,4]oxazino[2,3-f)quinoline (e.g., structures 19 and 20), is depicted in Scheme IV. The process of Scheme IV begins by treatment of a quinolinone with a lialogenating agent, for example, phosphorus oxychloride, to afford a compound of structure 19. Substitution of the halide can be accomplished by treatment with a nucleophile, for example, sodium methoxide in methanol, to afford a compound of structure 20. (Figure Removed) The asymmetric synthesis of Scheme V begins with the chemo- and regioselective A'-alkylation of a p-ammoalcohol, either as a single enantiomer (R or S) or its racemate, For example, (JR}-2-ammo-] -butanol, onto a 3,4-dihalonitrobenzene, for example, 3,4- difluoromtroherizene, to afford an optically pure arylamino alcohol (e.g., Structure 21). Treatment of ammo alcohol compounds such as Structure 21 with an aldehyde or the corresponding hydrate or hemiacetal, for example, tnfluoroacetaldehyde ethyl hemiacetal, in the presence of an acid catalyst, for example p-toluenesulfonic acid, affords an optically purs oxazoluiine compound (e.g., structure 22). Treatment of an oxazolidine compound such as structure 22 with a reducing agent, for example, triethylsllane, in the presence of an acid, for example, titanium tetrachlonde, affords an TV-alky! substituted ammo alcohol compound (e.g., structure 23). Benzoxazine compounds (e.g., structure 24), may then be formed by cyclization of the jY-alkyl substituted amino alcohol compounds (e.g., structure 23) by treatment with a base such as sodium hydride. Reduction of nitro benzoxazine compounds (e.g.. structure 24) with a reducing agent, for example, palladium on carbon under a hydrogen atmosphere, affords an aminobenzoxazine compound (e.g., structure 25). Treatment of a compound of structure 25 with an acylatmg agent, for example trimethylacetyl chloride, in the presence of a base, for example, pyndine, affords a compound of structure 26. Rb may be, in addition to /-butyl, an aryl or a stencally hindered alkyl substituent. Alternatively, it may be t-butoxy, aryloxy, or a stencally hindered alkoxy substituent. Regioselective lithiation of a compound of structure 26 with a strong base, for example, r-butyllithium followed by quenching with an acylatmg agent, for example, ethyl trifluoroacetate, affords a compound of structure 27. The base may be an alternative organolithium reagent, for example, sec-butyllithium or ?7-butyllithiurn. Treatment of a compound of structure 27 with a Horner-Emmons reagent, for example, (carbethoxvrnethylene)tnphenylphosphorane produces a compound of structure 28. Annulaiion of a compound of structure 28 to the pyridone ring may be accomplished by treatment of a compound of structure 28 with an acid, for example hydrochloric acid in acetic acid to afford a compound of structure 29. An enantiomer of structure 29, or a racemic mixture, may be obtained by the synthetic rouie as described in Scheme V, by starting with the enantiomer of the (3- aminoalcohoi as shown (e.g., an ()S)-j3-amino alcohol), or aracemic mixture of the (3- ammoaicoho! shown (e.g., a (-r-)-p-amino alcohol. Accordingly, an (iS}-(3-amino alcohol, employed in Scheme V, produces an (iSVquinolinone; an (jR)-(3-ammo alcohol, employed in Scheme V, produces an (-R)-quinolinone; and aracemic mixture of the P-amino alcohol, employed m Scheme V, produces a racemic mixture of the corresponding quinolinone. Scheme VI (Figure Removed) An alternative racemic route to nitrobenzoxazine compounds.of structure 24 (Scheme VI) begins with the //-alleviation of a 2-amino-5-nitrophenol nitrogen by treatment with an aldehyde, its corresponding hydrate or hemiacetal, with for example, tnfluoroacetaJdehyde hydrate in the presence of a reducing agent, for example, sodium cyanoborohydride, in an acid, for example trifluoroacetic acid. This procedure affords an A-'-alkyiated compound of structure 30. This can be further transformed by alkylation with a haloketone, for example, 2-bromobutanone, mediated by a base, for example, potassium carbonate, followed by treatment with a reducing agent, for example, sodium cyanoborohydride, in an acid, for example acetic acid, to afford a benzoxazme compound ii-'.e.. structure 24). Scheme V I I (Figure Removed) Scheme V'll descnbes a route to compounds of structure 34. A compound of structure- 5 is created with an amine, amide, or carbamate, for example butylamme, and a transition rneial. for example Pd?_(dba)3, in the presence of a ligand, for example BINAP, and a base, for example, cesium carbonate, to afford a compound of structure 31. Removal of the benzyl group with a reducing agent, for example palladium on carbon under a hydrogen atmosphere, affords a compound of structure 32. A compound of structure 32 is treated with an alpha-halo ester, for example, ethyl bromoacetate. in the presence of a base, for example potassium carbonate, to afford a compound of structure 33. A compound of structure 33 is hydrolyzed with an acid, for example, concentrated Hen in acetic acid, to afford a compound of structure 34. The compounds of the present invention also include racemates, stereo isomers and mixtures of said compounds, including isotopically-labeled and radio-labeled compounds. Sucii isomers can be isolated by standard resolution techniques, including fractional crystallization and chiral column chrornatography. As noted above, the steroid modulator compounds of the present invention can be combined in a mixture with a pharmaceutically acceptable carrier to provide pharmaceutical compositions useful for treating the biological conditions or disorders noted herein in mammalian and, more particularly, in human patients. The particular earner employed in these pharmaceutical compositions may take a wide variety of forms depending upon the type of administration desired. Suitable administration routes include enteral (e.g., oral), topical, suppository and parenteral (e.g., intravenous, intramuscular and subcutaneous). In preparing the compositions in oral liquid dosage forms (e.g., suspensions, elixirs and solutions), typical pharmaceutical media, such as water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be employed. Similarly, when preparing oral solid dosage forms (e.g., powders, tablets and capsules), carriers such as starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like may be employed. Due to their ease of administration, tablets and capsules represent a desirable oral dosage form for the pharmaceutical compositions of the present invention. For parenteral administration, the earner will typically include sterile water, although other ingredients that aid in solubility or serve as preservatives may also be included. Furthermore, injectable suspensions may also be prepared, in which case appropriate l i q u id earners, suspending agents and the like may be employed. For it ,-pical administration, the compounds of the present invention may be formulated using bland, moisturizing bases, such as ointments or creams. Examples of suitable ointment bases are petrolatum, petrolatum plus volatile silicones. lanolin and water in oil emulsions such as Eucerin™, available from Beiersdorf (Cincinnati, Ohio). Examples of suitable cream bases are Nivea™, available from Beiersdorf (Cincinnati, Ohio), eoid cream (USP), Purpose Cream™, available from Johnson & Johnson (New Brunswick, New Jersey), hydrophilic ointment (USP) and Lubiiderm™, available from vVamer-Lanibert (Morris Plains, New Jersey). The pharmaceutical compositions and compounds of the present invention will general!)- be administered in the form of a dosage unit (e.g., tablet, capsule, etc.). The compounds of the present invention generally are administered in a daily dosage of from about 1 ug/k;.; of body weight to about 500 mg/kg of body weight. Typically, the compounds of the present invention are administered in a daily dosage of from about 10 ug'kp; to about 250 mg/kg of body weight. Most often, the compounds of the present invention are administered in a daily dosage of from about 20 p-g/kg to about 100 mg/kg body weight. As recognized by those skilled in the art, the particular quantity of pharmaceutical composition according to the present invention administered to a patient will depend upon a number of factors, including, without limitation, the biological activitydesired, ihe condition of the patient and the patient's tolerance for the drug. The compounds of this invention also have utility when labeled (e.g., radiolabeled, isotopically-labeled and the like) as ligands for use in assays to determine the presence of A.R in a cell background or extract. They are particularly useful due to their ability to selectively activate androgen receptors and can therefore be used to determine the presence of such receptors in the presence of other steroid receptors or related mtracelluiar receptors. Thus, the invention provides methods of determining the presence of androgen receptors (AR) in a cell or cell extract. These invention methods comprise contacting the cell or cell extract with the compounds of the present invention which have been labeled and testing the contacted cell or cell extract to determine the presence of AR. Testing can be accomplished via testing for activation oi androgen receptor(s) (e.g., via elevated presence of the product of androgen mediated process(es)). via separation of the bound compound/receptor combinauon and the like, which techniques are known to those of skill in the art. Due to the selective specificity of the compounds of this invention for steroid receptors, these compounds can be used to purify samples of steroid receptors in vitro. Such purification can be earned out by mixing samples containing steroid receptors with one or more o i" the compounds of the present invention so that the compounds bind to the receptors of ciioice and then isolating the bound ligand/receptor combination by separation techniques which are known to those of skill in the art. These techniques include column separation, filtration, centnfugation, tagging and physical separation and antibody complexmg, among others. Thus, the invention also provides methods for purifying samples of steroid receptors in vitro. Invention methods comprise contacting a sample containing steroid receptors with one or more of the compounds of the present invention so that the compounds bind to the steroid receptors to form a bound compound/receptor combination and separating out the bound compound/receptor combination. The compounds and pharmaceutical compositions of the present invention can. be used in the treatment of the diseases and conditions described herein, hi this regard, the compounds and compositions of the present invention may prove particularly useful as modulators of male sex steroid-dependent diseases and conditions (e.g., process(es) mediated by androgen receptors) such as the treatment of acne, male-pattern baldness, sexual dysfunction, wasting diseases, hirsutism, hypogonadism, prostatic hyperplasia, osteoporosis, impotence, cancer cachexia and various hormone-dependent cancers, including prostate and breast cancer. The compounds of the present invention may also prove useful in male hormone replacement therapy, stimulation of hematopoiesis, male contraception and as anabolic agents. As utilized herein, the term "modulate" includes the ability of a modulator for a member of the androgen. receptor family to either directly (by binding to the receptor as a ligand) or indirectly (as a precursor for a ligand or an inducer which promotes production of ligand from a precursor) induce expression of gene(s) maintained under hormone expression control, or to repress expression of gene(s) maintained under such control. Thus, both inhibitory effects on androgen receptors and activating effects on androgen receptors are contemplated within the scope of modulation. The compounds of the present invention may be extremely potent activators of AR. displaying 50% maximal activation of AR (e.g., activation of AR, determined by measurement of luciferase production levels compared to levels achieved by diliydrotestosierone (DHT)) at a concentration of less than 100 nlVl (Cotransfection assay concentration), at a concentration of less than 50 nM, at a concentration of less than 20 njvl, or even at a concentration of 10 nM or less. (See, for example, Biological Examples.) In addition, selected compounds of the present invention may be extremely potent antagonists of AR, displaying 50% maximal inhibition of AR (e.g., inhibition of AR, determined by measurement of luciferase production levels compared to levels achieved by dihydrotestosterone (DHT)') at a concentration of less than 100 nM (Cotransfection assay concentration), at a concentration of less than 50 nM, at a concentration of less than 20 nM, or even at a concentration of 10 nM or less. (See, for example. Biological Examples.) Selective compounds of the present invention generally do not display undesired cross-reactivity with other steroid receptors, as is seen with the compound mifepristone (RU486; Roussei Uclaf). a known PR antagonist that displays an undesirable cross reactivity on GR and AR, thereby limiting its use in long-term, chronic administration. The invention will be further illustrated by reference to the following non-limiting Examples. . EXAMPLE 1 (37?)-23.4J-'reti-ahydro-3-methvl-10-(trifluoromethvD-8H-rL41oxa2inor2.3-/1quinolin-8- one (Compound 10.1. Structure 9 of Scheme II, where R1, R3. R4, R5. = H. R2 = trifluoromethyL Rf) = Me) 5-Am]no-7-cljoro-3_.4-dihydrQ-4-hydrQxy-4-(trifluoromethvl)-l//-quiiiplin-2-one: To a solution of 5-chloro-l,3-phenylenediamine (15.0 g, 0.105 mol) in 70 mL ethanol was added ethyl 4,4.4-trifluoroacetoacetate (20.4 g, 0.111 mol), then the mixture was heated at reflux for 1S Ji. The solvent was removed under reduced pressure until the product began to precipitate. The material was allowed to crystallize for 2 h, whereupon it was filtered and rinsed with cold ether to afford 10.9 g (37%) of 5-araino-7-chloro-3,4-dihydro-4- hydroxy-4-itr',fluoromethyl)-l/f-quinolin-2-one, a tan solid. The filtrate was concentrated until solid began to precipitate and afforded an additional 3.0 g (10%). *H NMR (400 MHz, acetorit-ds) 5 11.0 (broad s, IH), 9.64 (s, IH), 7.42 (t, IH, J= 8.1), 6.99 (d, IH. J = S . l j . o.9U(s, IH). 6.79 (d, IH,J=8.1). 5-Aminp-3.4-dihydro-4-hydroxy-4-(trifluoromethylVlAr-quinolin-2-one (Structure 2 of Scheme K where R1. R7. R° = H. R2 = tnfluoromethyl): A mixture of 5-ainino-7- c.hloro-3,4-dihydro-4-hydroxy~4-(trifluoromethyl)-lf/'-quinolin-2-oiie (8.0 g, 28 mmol), KOAc (5.6 g, 57 mmol) and 10% Pd-C (4.0 g) in 200 mL ethanol was stirred under an atmosphere o f hydrogen for 2 h. The mixture was filtered through Celite and concentrated under reduced pressure. The resultant solid was dissolved in EtOAc (250 mL) and washed sequentially with saturated NaHCOs (200 mL) and brine (200 mL), dried over MgSOd, filtered and concentrated to afford 7.0 g (100%) of 5-amino-3,4-dihydro-4-hydroxy-4- (mfluorornethyl)-l//-quinolin-2-one, a foamy tan solid. !H NMR (400 MHz, acetone-dh) 5 9.16 (broad s, 1 H), 6.99 (t, IH, J= 8.0), 6.44 (broad s, IH), 6.39 (d, IH, J= 7.9), 6.26 (d. IH. .7 -= 7.i : '), 5.44 (broad s, 2H): 3.09 (d, AB, J= 17.0), 2.93 (d, AB,J= 17.0). 5-Hvdroxv-4-(tnfluoromethvlVl//-qumolm-2-one (Structure 3 of Scbeme I. where R'_. R ; . R ' = ,H. R" = .trifluoromethvl): To a solution of 5-amino-3,4-dihydro-4-hydroxy-4- (tnlluoromethyr)-lH'-quinolin-2-one (6.0 g, 24 mmol) in 100 mL 4.8 M H9S04 Avas added a solution of NaNO2 (1.85 g, 26.8 mmol) in 6 mL water at 0°C. The reaction mixture became deep red. This solution was transferred to 120 mL 1OM jEbSCV preheated to 145°C. The mixture was heated at 145°C for 0.5 h, then poured into 400 g of ice water. The crude solid was adsorbed onto silica gel and eluted with 9:1 CH^C^MeOH to afford 4.6 g (82° V) of :)-hydi-oxy-4-(trifluoromethyl)-l//-quinolin-2~one, an off-white solid. 'H NMR (400 MHz, acetone-d6) 5 11.0 (broad s, 1H), 9.64 (s, 1H), 7.42 (t, 1H, J= 8.1), 6.99 (d, IH, ,/=' S. I), 6.90 (s, 1H), 6.79 (d, 1H, J= 8.1). 6-Bromo-5-hydroxy-4-(tnfluoromethyl)-17fjr-quinolin-2-one (Structure 4 of Scheme [, where R1, R'. R8 ~ H. R2 = tnfluoromethyl): To a solution of 5-hydroxy-4- (tnfluorometh\T)-l./:/-qumohn-2-one (4.38 g, 19.1 mmol) and diisopropylamine (14 mL, 1(.)0 rruTiol) iri 100 mL EtOAc was added a solution of N-bromosuccinimide (3.74 g, 21.0 mmol) in 70 mL EtOAc at ~10°C over 30 mm. The reaction mixture was stirred for 1 h, then acidified to pH 1 by the addition of 6M HC1. The mixture was extracted with EtOAc ( 3 x 150 mL! and the combined organic layers were washed with brine (200 mL), dried over MgSQj filtered and concentrated under reduced pressure. Recrystallization from chloroform: hex ;uies afforded 4.5 g (77%) of 6-bromo-5-hydroxy-4-(trifluoromethyl)-l//- qumolin-2-one, an off-white solid. Rf 0.4 (1:1 EtOAcihexanes); lll NMR (400 MHz, acetone-dh) o 11.1 (broad s, IH). 8.75 (broad s, IH), 7.76 (d, IH, J= 8.8), 7.04 (d, 1H, J = S.S), 6.'8 is. I H ) . 5-Beti2yioxy-6-bromo-4-(trifluoromethyl)-l-/:f-quinolin-2-one: To a suspension of 6-bromo-5-hyd!'oxy-4-(trifluoromethyl)-l/7-quinolin-2-one (9.42 g, 30.6 mmol) and CsF ( i 3.9 g, 91." mmol) in 102 mL DMF was added benzyl bromide (6.54 g, 38.2 mmol) dropwise. After 24 h, the mixture was poured into 0.1 M NaHSC>4 (500 mL) and extracted with EtOAc ( 1 : 1 ' ) . The aqueous layer was reextracted with EtOAc (500 mL) and the combined organic layers were washed sequentially with water (500 mL), bnne (300 mL), dned over MgSO4, filtered and concentrated to a slurry. The mixture was cooled to 0°C, filtered and the resultant solids washed with cold EtOAc to afford 7.26 g (60%) of 5- benzyloxy-6-bromo-4-(trifluoromethyl)-lJ7-quiiaolin-2-one, a tan solid. R,-0.26 (7:3 hexanes:acetone): ]H NMR (400 MHz, acetone-d6) 6 11.3 (broad s, IH), 7.91 (d, IH, J = 9.0. IH), 7.CK (d. 2H. J= 7.3), 7.43 (t, 2H. J= 7.2), 7.25-7.35 (m, IH), 7.32 (d, IH, / = 9.0), "1)6 (sr IB), 5.10(s, IH). 5-Benzyloxy-6-bromo-2-isoprppoxy-4-(tri£luoromethvl)quinoIine (Structure 5 of Scheme I, where R.1, R7, Rs = PL R2 = trifluoromethyl): To a suspension of 5-benzyloxy- 6-bromo~4-(tnfluoromethyl)~l//-quinolin-2-one (11.7 g, 29.4 mmol) and CsF (17.8 g, 117 mmol) m 150 ml. DMF was added isopropyl iodide (19.9 g, 117 mmol). After 28 h, the mixture was partitioned between EtOAc (500 mL) and water (250 mL) and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with water (200 mL), brine (100 mL), dried over MgSO4, filtered and concentrated to afford 13 g (100%) of 5-benzyloxy-6-bronio-2-isopropoxy-4-(trifluoromethyl)quinoline. 'H NMR (400 MHz, CDCl3j 8 7.85 (d. 1H, J= 9.0), 7.55-7.65 (m, 3H), 7.38-7.48 (m, 2H), 7.32- 7.38 (m, 1H), 7.33 (s, 1H), 5.54 (sept, 1H, J= 6.2), 5.06 (s, 2H), 1.42 (d, 6H, J= 6.2). ('-Brom()-5-hydroxy-2-isoprQpQXv-4-(trifluQromethyI)quinoline (Structure 6 of Scheme I. where R1, R'. Rs_= H. R2 = trifluoromethyl): A solution of 5-benzyloxy-6- bromo-2-isopropoxy-4-(tnfluoromethyl)qmnolme (13.5 g, 30.S mmol) in 31 mL methanesulibriic acid and 31 mL acetic acid was stirred at rt for 10 h, whereupon it was poured in water (500 mL), neutralized with K^COs (ca. 75 g) and extracted with EtOAc (3 x 200 rnL). The combined organic layers were washed with brine (200 mL), dried over MgSOa, filtered and concentrated. Flash chromatography (2%-5% EtOAcrhexanes, gradient elation) afforded 9.9 g (92%) of 6-bromo-5-hydroxy-2-isopropoxy-4- ('tritluoromethyOquinoline, a yellow-brown oil. 'H NMR (400 MHz, CDC13) 87.71 (d, lH..y = 9.1). '.38 (d, 1H, J = 9.1), 6.23 (s, 1H), 5.53 (sept, 1H, .7=6.2), 1.41 (d, 6H,/ = 6.2). arvunoalcohol. To a solution of the bromophenol substrate (1 equiv). the /V-Boc-protected ammoalcoho! (16 equiv), triphenylphosphine (1.6 eqniv) and JV-methylmorpholine (10 equiv) m dry THF (0.1-0.2 M) was added dhsopropyl azodicarboxylate (1.6 equivj dropwise. producing an orange color. After 5 min. the ice bath was removed and the reaction was stirred at rt for 2 -16 h. The reaction mixture was poured into water (40 raL/mmol), neutralized with 1.0 M HC1 and extracted with EtOAc (2 x 25 mL/mmol). The combined extracts were washed with of 0.1 M HC1 (20 mL/mmol) and brine (20 mL/mmol), dried over MgSO4, filtered, concentrated. Column chromatography (hexane:EtOAc) afforded the desired arvi ether. (2'j?V6-Bromo-5-[(2'-f-butoxycaT:1bonylaminoVr-proppxv]-2-isopropoxv-4- (trifluoromethynquinoline (Structure 7 of Scheme II. where R\-R3; R4. R3, = H, R2 = trifluoromethyl. R" — Me): The compound was prepared according to General Method 1 (EXAMPLE 1 ) from 6-bromo-5-hydroxy-2-isopropoxy-4-(tnfiuoromethyl)quinoline (0.50 g, 1.43 rnmoi), (7?)-/V-Boc-almol (400 mg, 2.28 mmol), triphenylphosphine (600 mg, 2.2S mmol) and diisopropyl azodicarboxylate (0.45 ml, 2.28 mmol) in 0.6 mL Nmethylmorphoiine in 14 mL dry THF to afford 484 mg (67%) of (27?)-6-bromo-5-[(2Wbutoxycarbonyiamino)- 1 '-propoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline after flash diromatograpby (100% hexanes to 6:1 hexanes/EtOAc, gradient elution). 'H NMR (500 MHz. CDC1 .:) ,5 7.80 (d, ,/= 9.3, 1H), 7.56 (d, J= 8.8, 1H), 7.30 (s, 1H), 5.53 (sept, 7 = 0.4, 1H), 4.95 (bs, 1H), 4.18 (m, 1H), 3.9S (m, 1H), 3.94 (m, 1H), 1.46 (s, 9H), 1.41 (d, 7 -6A6H), 1 37 (d, 7=6.8, 3H). General Method 2: Hydrolysis of a /-butoxycarbonyl protected amine. To a solution of the carbamale substrate in CHiCli (0.2 M) was added an equal volume of TFA and the solution was stirred at it for 1 h. The mixture was poured into water (100 mLmmol), neutralized with 6 M NaOH and extracted with EtOAc (2 x 50 mL/mmol). The combined extracts were washed sequentially with saturated NaHCO3 (50 mL/mmol) and brine ( S i ' mL/mmol), dried over MgSC>4, filtered and concentrated. Column chromatography (CH^CL/MeOH) afforded the desired free amine. ( trifluo ro met h y 1 )qumo line : This compound was prepared according to General Method 2 (EXAMPLE 1 ') from (27?)-6-bromo-5-[(2 V-butoxycarbonylamino)- 1 '-propoxy]-2- isopi-opoxy-4-('trifluoromethyl)quinoline (480 mg, 0.95 mmol) in 5 mL CH2C12 and 5 mL TFA to afford 346 mg (90%) of (2'^)-6-bromo-5-(2'-amino-r-propoxy)-2-isopropoxy-4- (tnfluoromethyi)qumolme. 'H NMR (500 MHz, CDC13) 5 7.81 (d, 7- 8.8, 1H), 7.57 (d, ]---• 9.3, Hi), '.30 (s, 1H), 5.53 (m, 1H), 3.93 (m, 1H) 3.84 (m, 1H), 3.66 (m, 1H), 2.33 (bs, 2IT), ! .41 (d, 7 ••--= 6.4, 3H), 1.40 (d, 7= 6.4, 3H), 1.22 (d, 7= 6.4, 3H). General Method 3: Palladium catalyzed coupling of an amine with an aryl bromide. To a mixture of (±)-2,2'-bis(diphenylphosphino)-l,r-binaphthyl (4-10 mol %), Pdjfdba); (2-5 mol%). sodium /-butoxide (1.4 equiv) was added a solution of the amino ary! bromide (1 equiv) in toluene (0.1-0.2 M). The reddish solution was heated at 90- 1 00°C for o-24 h, whereupon it was poured into cold saturated NH4C1 (20 mL/mmol). The mixture was extracted with EtOAc (2 x 40 mL/mmol) and the combined organic layers were washed with brine, dried over MgSO^, filtered and concentrated. Flash chromatography (hexanes :EtOAc) afforded the desired 2H-[l,4]oxazino[2,3-/]quinolme. (?^)-3,4-pihydrp-8-jsopropoxy-3-methvl-10-ftri£luQromethvl)-2//'- [ 1 -41ox:izmo|2.3-/1qumolme (Structure 8 of Scheme II. where R1. R3. R4, R5. =H. R2 = IrifluorornethyL Rb - Me): This compound was prepared according to General Method 3 (EXAMPLE 1) from (2'7?)-6-brorno-5-(2'-amino-r-propoxy)-2-isopropoxy-4- (tniluoromethyi)qumolme (346 mg, O.S5 mmol), (±)-2.2'-bis(diphenylphosphino)-l,rbmaphthyl (2 1 mg, 4 mol%), Pd2(dba)3 (15.6 mg, 2 mol%), sodium /-butoxide (1 14 mg, 1.1'} mmol) to afford 190 mg (70%) of (S./O-SAdihydro-S-isopropoxy-SHmemyl-lOUnfluoromethyl^/^ l^Joxazinopp-^quinoline after purification by flash chromatography (100% hexanes to 4:1 hexanes:EtOAc, gradient elution). ]H NMR (500 MHz. CDC1-; i 6 7.36 (d, /= 8.8, 1H), 7.18 (s, Hi), 7.03 (d, J= 8.8, Hi), 5.47 (m, 1H), 4.33 (del,./- 10.7: 2.9, 1H), 3.78 (dd,./ = 10.7, 8.1, 1H), 3.74 (bs, 1H), 3.66 (m, 1H), 1.38 (d, ,/ ••= 5.1.', 311). 1.37 id, /= 6.4, 3H), ! .24 (d, .7= 6.4, 3H). General Method 4: Acid mediated hydrolysis of an isopropyl imino ether to a pyndone. A solution of the imino ether in a 3: 1 acetic acid:concentrated HCI (0. 1-0.2 M) solution was heated oO-100°C for 4-16 a. The solution was poured into saturated NaHCO> (80 ;nL/mmol), extracted with EtOAc (2 x 80 niL), dried over MgSO4, filtered and concentrated and purified as indicated. /1c|uinolm-8-one (Compound 101. Structure 9 of Scheme II, where R1, R3. R4. R5. = H. R2 flJSiflty^Hngthvj.'R^j^e): Compound 101 was prepared by General Method 4 (EXAMPLE 1) from (]?)-3,4-dihydro-8-isopropoxy-3-methyl-10-(trifluoromethyl)-2/f- [1 ,4joxazinoi 2,3-_/]quinoline (14 mg, 0.043 mmol) in 1:1 acetic acidxoncentrated HCI (0.01 M) heated at 90°C for 4 h to afford 7 mg (58%) of Compound 101, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes :EtOAc, gradient elution). 'H NMR (500 MHz, CDC13) 5 12.37 (bs, 1H), 7.13 (s, 1H), 6.94 (d, J= 8.79, 1H), 0.92 (d. ./= 8.79, 1H), 4.34 (dd, J= 10.74, 2.93, 1H), 3.79 (ad, J= 10.74, S.10, 1H), ?.69(bs, 1H). 3.62 (m, 1H), 1.24 (d, /= 6.35, 3H). EXAMPLE 2 (3^)-2J,4.7-Tefraliydro-3.4-diinethvl-l'Q-(triflaoromethvl')-8ff-[1.41oxazinor2,3- /1qumoim-8-one (Compound 102. Structure 11 of Scheme II, where R1. R3. R4. R5. = H. R: •= trifluoromethyl,_R6 = Me. R13 = CEh) General Method 5: Reductive animation of a 2/f-[l,4]oxazmo[2,3-/]qumoline or an 8f/-| L4]oxazmo[2,3~/]qumolin-S-one derivative with sodium cyanoborohydride and an aldehyde, its hydrate, or its hemiacetal. A solution of the 2fl"-[l,4]oxazino[2,3-/]qumolme or 8//-[1.4]oxazmo[2,3-/]qurnolin-8-one (1 equiv) and the aldehyde, its hydrate or hemiacetal ( 1 0 equiv) in acetic acid or tnfluoroacetic acid, was stirred at room temperature for 2 h, whereupon sodium cyanoborohydride (5 equiv) was added portionwise. The solution was stirred for 12-24 h at it, then poured into cold saturated NaHCOs (pH 8-10). The aqueous layer was extracted with EtOAc (2 x 40 mL/mrnoI) and the combined organic layers were washed with brine, dried over MgSC>4, filtered, concentrated and purified as indicated, or used directly in the next step. (3/?)-2.3,4.7-lTetrahvdro-3.4-dimethvl-10-('tnfluoromethvl)-8/jr-ri.41oxazmor2.3- ./.Muinplm-8-u.ne (Compound 102,.Structure 11 of Scheme II. where R\ R3, R4. R5, = H, R_'_ -:; tnjliioroinethyL R = Me. R1'1 = CLU): Compound 102 was prepared according to General Method 5 (EXAMPLE 2) from (3./?)-3,4-dihydro-S-isopropoxy-3-methyl-10- (trifiuoromethyl)-2/f-[ l,4]oxazmo[2,3:/]qmnolme (12 mg, 0.04 rnmol), 37% fonnaldehycie solution (0.010 mL, 0.2 mmol, 5 equiv) and NaCNBH3 (10 mg, 0.2 mniol, 5 equiv) in 1 ml, AcOH (0.04 M) to afford 9 mg (ca. 70%) of (J?)-3,4-dihydro-Sisopropoxy- 3.4-dimethyl-10-(trifluoromethyl)-2//-[l34]oxazmo[2,3-/]quinoline. This material (9 mg, 0.03 mmol) was taken on directly according to General Method 4 (EXAMPLE 1) by treatment with 3 mL acetic acid and 3 mL concentrated HC1 and heated at 90°C for 4 h to afford 7 mg (89%) of Compound 102 after flash chromatography (3:1 hexanes:EtOAc TO 1:1 hexanes:EtOAc, gradient elution). ]H NMR (500 MHz, CDC13) 6 11.00 (bs, i H ) , 7.12 (s, 1H), 7.01 (d, J= 9.3, 1H), 6.96 (d, J= 9.3, 1H), 4.19 (dd,J= 10.7, 2.(L IHl 4.1 i (dd, J= 10.7, 3.7, IH), 3.43 (m, IH), 2.93 (s, 3H), 1.21 (d, /= 6.8, 3H) EXAMPLE 3 (3./?)-4-£tbvL2,:x4j4etrahydi-o-3-mefhyl-10-(trifluoromeflivl)-8ff4L4]oxa2rno[2.3- /|qumolin-8-one (Compound 103. Structure 11 of Scheme II, where R1, R3, R4, R5, = H. R:? = trifluoromethyl, R6 = Me. R13 = OHkCHQ General Method 6: Reductive amination of a 2/7-[l,4]oxazino[2.3-/]qmnoline or an 8/7 [1.4]oxazmo[2,3-/]quinolm-2-one with sodium borohydride with acetic acid or a substituted acetic acid. To a solution of the 27rf-[l,4]oxazino[2,3-/]qumoline or SH- [T,4]oxazmo[2,3:/]quinolm-2-one in a substituted acetic acid was added NaBEU. pellets (5- 10 equiv). After 12-24 h, the reaction was carefully poured into cold saturated NaHCCh. The aqueous layer was extracted with EtOAc (2 x 40 mL/mmol) and the combined organic layers were washed with brine, dried over MgSCU, filtered, concentrated and the compound was purified as indicated. ;'3A')-4-Ethvl-23,4,7-tetralivdro-3-methvl-lQ-(trifluoromethyn-8//- [1.4ioxazino[2.3-/1qmnolin-8-one (Compound 103, Structure 11 of Scheme II. where R1. R:\ R4. R-, -= 1:1, R2 --= tnfluoromethvL R° = Me, R13 = CHZCHQ: This compound was prepared according to General Method 6 (EXAMPLE 3) from (3fl)-3,4-dihydro-8- isopropoxy-3--methyl-10-(trifluoromethyl)-2/f-[l,4]oxaznio[2,3-/]quinolme (16 mg, 0.049 rnmol) and NaBtLi pellets (large excess. >10 equiv) m 5 mL acetic acid (0.01 M stirred at rt for 12 h. to ;:ifford IS mg (100%) of (3/t)-4-ethyl-3,4-dihydro-8-isopropoxy-3-methyl- 10-( tniluoromethyl.)-2/7- 1,4]oxazino[2,3-/]quinoline. This material (ISmg, O.OSOmnio]) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 2.5 mL acetic acid and 2.5. mL concentrated HC1 and heated at 90°C for 4 h to afford 9 mg (57%) of Compound 103, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes:EtOAc, .gradient elution). 'H NMR (500 MHz, CDC13) 5 12.02 (bs, 1H), 7.12 (s. 1 H), 7.04 (d, J = 8.8, 1H), 6.97 (d, J = 9.3, 1H), 4.10 (dd, J= 10.2, 3.4, 1H), 4.02 (dd, .7 = 10.3.2.9. 1H), 3.53 (m, 1H), 3.43 (m, 1H), 3.32 (m, 1H), 1.22 (d,,7= 6.9, 3H), 1.18(t.7 -M.3F1). EXAMPLE 4 f3^)-2.3.4^--1'etrahvdro-3-methyl-442.2,2-trifluoroethvlV10-(trifluorQmethyl)-8ff- [l,41oxaziru)!'2.3T/lquinolin-S-one (Compound 104, Structure 11 of Scheme IL where R . R:i. R4. R-\ •-- IL R2 - trifluoromethyl, R6 = Me. R13 = This compound was prepared according to General Method 6 (EXAMPLE 3) from (3/f)-3^4-(lil}ydro-8-isopropoxy-3-methyl-10-(trifluoromethyl)-2Ar-[l,4]oxazino[2,3- /Iquinoline (4 mg, 0.01 mmol) and NaBH4 pellets (large excess, >10 equiv) in 2.5 mL tnfluoroacetic acid (0.005 M) stirred at rt for 12 h, to afford 4 mg (80%) of (^)-3,4- di]iydro-8-]SC)propoxy-3-methy]-4-(2,2,2-tnfJuoroetliyl)-10-(trifluoromethyl)-2jt/- l,4|oxazino[2,3-y]quinoline. This material (4 mg, 0.01 mmol) was carried on according to General Method 4 (E'XAMPLE 1) by treatment with 2 mL acetic acid and 2 mL concentrated HC1 (0.003 M) and heated at 90°C for 4 h to afford 3.2 mg (71%) of Compound 104, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes:EtOAc, gradient elution). JH NMR (500 MHz, CDC13) 5 12.00 (bs, 1H), 7.16 (s, 1 H). 7.11 (d. J - 9.3, 1H), 7.00 (d, ./= 8.8, 1H), 4.20 (d, J= 10.7, 2.9, 1H), 4.09 (dd, ./ = 10.7,24, l i i ) . ?.82(jn, 2H), 3.60 (m, 1H), 1.26 (d, J= 6.8, 3H). EXAMPLE 5 L.MKL :LiLI ..retrahv_d_ro-3-methvl-4-propyl-10-(tnfluorQmethvl')-8/7r-ri.4]oxazmq[23- ;1quinoJin-8-oiie (Compound JOS. Structure 11 of Scheme II, where R1, R3, R4, R5. = H, Phis compound was prepared according General Method 6 (EXAMPLE 3) from i.3/0-3.4-dJhvdro-8-isopropoxy-3-methyl-10-(trifluoromethyl)-2//-[l,4]oxazino[2,3- yjqumok'ne ( 1 1 mg, 0.03 mmol), propionaldehyde (0.3 mmol, 1 0 eq) and NaCNBHs (10 equiv) m 4 nil. T.FA (0.03 M) stirred at rt for 12 h to afford 12 mg (100%) of (^)-3,4- dihydro-8->is()propoxy-3-methyl-4-propy3-10-(trifluoromethyl)-2//-[l,4]oxazino[2,3- /Icjumoline. This material (12 mg, 0.030 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with 3 mL acetic acid and 3 mL concentrated HC1 and heated at 90°C for 4 h to afford 8 mg (75%) of Compound 105 after purification by silica gel chromatography (3:1 hexanes :EtO Ac to 1:1 hexanes:EtOAc, gradient elution). ]H NMR (500 MHz, CDC13) 5 11.15 (bs, 1H), 7.10 (s: 1H), 6.99 (d. J=8.8, 1H), 6. 88 (d, J-8.8, 1H), 4.11 (dd,J = 10.7,3.2, 1H), 4.03 (dd, J= 10.7, 2.4, 1H), 3.51 (m, 1H), 3.30 (m, 1H), 3.14 (m, 1H), 1.64 (m, 2H), 1.21 (d, J= 6.4, 3H),- 0.97 (t, J = 7.3, 3H). • EXAMPLE 6 Llrrb'Mlii- 2.3,4.7-tetrahvdro-3-methvl-10-(tiifluoromethyl)-8fir-ri.41oxazinor2.3- /iquinolin-S-one ('Compound 106, Structure 11 of Scheme II, where R1,_RJ, R , R , = H, R: = rniluoromethvl. R6 = Me, R13 = -CHaCENCH?) To a suspension of (^)-3,4-dihydro-S-isopropoxy-3-methyl-10-(trifluoromethyl)- 2H-[l ,4]oxazmo[2,3:/]qumolme (13 mg, 0.04 mmol) and K2CO3 (28 mg, 0.2 mruol, 5 eq) in 1 mJ DMF (0.04 M) was added allylbromide (0.03 mL. 0.4 mmol, 10 eq). The reaction was heated to 50°C and allowed to stir for 12 h, whereupon the reaction was poured into 10 mL water and neutralized with IN HC1. The aqueous layer was extracted with EtOAc (2 x 40 mL/mmol) and the combined organic layers were washed with bnne, dried over Na2SCL. filtered, concentrated to afford 10 mg (75%) of (#)-4-allyl-3,4-dihydro-8- isopropoxy-?-methyl- 10-(trifluoromethyl)-2^r-[l,4]oxazino[2.3-/]quinoline. This material ( i 0 mg, 0.03 mmol) was earned on directly according to General Method 4 (EXAMPLE 1) by treatment with 1 mL concentrated HC1 (0.01M) and heated at 50°C for 6 h to afford 6 nig (67%) i if 'Compound 106 after silica gel column chromatography (gradient 3:1 hexanes:EiOAc to 1:1 hexanes:EtOAc. gradient elution) 1J3. NMR (500 MHz, CDC13) 8 11.89 (bs, LIT), :'.! 1 (s, 1H), 7.00 (d, ./= 8.8, 1H), 6.93 (d, /= 8.8, 1H), 5.86 (m, 1H), 5.24 (in, 2H), 4.10 (m. 2H), 3.90 (m, 2H), 3.55 (m, 1H), 1.22 (d, J= 6.8, 3H). EXAMPLE 7 (3/^o-Ethvl-2.3-4,7-tetrahvdro-lQ-(trifluoromethvl)-8flr-[L41oxazino[2.3-/r]qumolin-8- one (Compound 107. Structure 9 of Scheme II. where R1. R'. R4, R3, = H. R2 = trifluoromethyl. R6 = ...Et) (2)-6-Bromo-5-[(2'-/-butoxycarbonvlaminoV 1 '-butoxy]-2-isopropoxy-4- (niiluQromethvDqumoline f Structure 7 of Scheme II, wfhere R1, R3. R4. R3. = H, R2 = inilMQn-HSsthvLJ^LflEt): This compound was prepared according to General Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinoline (1.5 g, 4.4 mmol). (2^)"2--/V-r-butoxycarbonylamino-l-butanol (1.5 g, 7.8 mmoi), unphenvlphospliine (2.0 g, 7.8 mmol), DIAD (1.5 mL, 7.8 mmol) and N- 51 methylmorpholine (2.0 mL) in THF (40 ml) to afford 1.7 g (74%) of 6-bromo-5-[(2'-/- butoxycarbonylamino)-! '-butoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline as a tan solid. Rr 0.4 (9:1 hexane:EtOAc); JH NMR (400 MHz, CDC13) 5 7.80 (d, 1H, J= 8.9), 7.55 (d, 1H../- 8.9), 7.29 (s, 1H), 5.52 (septet 1H, J= 6.3), 4.80 (broad s, 1H), 4.06-3.90 (m. 3Hi, 1.91-1.81 (m, 1H), 1.71-1.59 (m, 1H), 1.46 (s, 9H), 1.41 (d, 6H, J= 6.2), 1.01 (t, 3H,.7=7.4V (3>-:3-Ethv]-3.4-dihydro-S-isopropoxv-10-('trifluoromethv])-2//-['l,4]oxazino[2.3- /Iqumoime (Structure 8 of Scheme II, where R1, R3. R4. R\ = H. R2 = trifluoromethvL R6 !L.Mtl: This compound was prepared according to General Method 2 (EXAMPLE 1) from 6-bromo-5-[(2'-r-butoxycarbonylamino)-r-butoxy]-2-isopropoxy-4- (tnfluoromethyl)quinoline (1.3 g, 2.5 mmol) in CH2C12 (10 mL) and TFA (10 mL) to afford 1.0 g (95%) of (2'/?)-6-bromo-5-(21-ammo-r-butoxy)-2-]sopropoxy-4- (tniluoroinethyl)quinoline. This material (1.0 g, 2.4 mrnol) was carried on according to General Method 3 (EXAMPLE 1) by treatment with Pd2(dba)3 (0.043 g, 2 mol%),, BINAP (0.059 g, 4 mol%) and /-BuONa (0.32 g, 3.3 mmol) in toluene (10 mL) heated at reflux to afford 0.51 g (63%) of (3^)-3-ethyl-3,4-dmydro-S-isopropoxy- lO-(trifluoromethyl)-2#- [ ,4 loxozmo 2,3:/]qumomie, a yellow solid. Rf 0.4 (9:1 hexane:EtOAc); !H NMR (400 MHx. CDClx) 5 7.36 (d, 1RJ = 8.8), 7.18 (sr 1H), 7.03 (d, \R,J= 8.8), 5.47 (septet. 1H, ./ = i).2). 4.3b (ad, ABX, 1H, ./== 10.6, 2.9), 3.87 (dd, s. Hi), 3.48-3.40 (m, 1H), 1.63-1.53 (m, 2H), 1.38 (d, 6H, J= 6.2), 1.06 (t, 3H, J= 7.4). (3jR)-3-Ethvl-2.3.4J-tetrahvdro-10-(trifluoromethvl)-8^-ri.41oxazinor2,3- ll£iUno!mri:ne (Compound 107. Structure 9 of Scheme II, where R1. R3. R4, R5. = H. R2 = trifluoromethvL R° -= Efl: Compound 107 was prepared according to General Method 4 (EXAMPLE 1) from (3^)-3-ethyl-3,4-dihydro-S-isopropoxy-10-(trifluoromethyl)-2H- [ 1,4|oxa2i.no| 2,3-/]qmnolme (0.220 g, 0.646 mmol) in cone. HC1 (1.0 mL) in AcOH (2.0 mL) heated a; 90°C to afford 0.190 g (98%) of Compound 107, a yellow solid. R,- 0.4 (9:1 CH2Cl2;MeOH); JH NMR (400 MHz, CDC13) 5 12.63 (broad s, 1HV 7.12 (s, 1H), 6.96 (d, 1 R, J = S.6). o.')2 (d, 1H, J= 8.6), 4.36 (dd, ABX, 1H, J= 10.3, 2.8), 3.86 (dd, ABX, 1H, J = 10.6, -.8), .3.77 (broads, 1H), 3.43-3.33 (m, 1H), 1.62-1.50 (m, 2H), 1.05 (t, 3H, J = EXAMPLE 8 (3^)-3-Ethvl-23.4J-teti-ahvdro-4-methvl-10-(trifluor6methvn-8flr-ri.41oxazinor2,3- /]guinolin-8-one (Compound 108, Structure 11 of Scheme II, where R\ R3. R4. Rs, =H. R2 =- tniluoroinethvl R6 = Et. R13 = CH3) (. j)-3-BthY]:3,4-di^vjro-8-isopropQXY-4-methyl-lQ-(trifluoromethy])-2gf I.41oxaziHor2.3-/1quinoline (Structure 10 of Scheme II, where R1. R3. R4. R5. =H. R2 = tniliiorometb-vL Rb ~ Et, R13 ~ CH-Q: This compound was prepared by General Method 5 (EXAMPLE i:)iTom(3J?)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(tnfluorometliyl)-2Jfir- [L4]oxazmo[2,3-/]qumoline (0.015 g, 0.044 mmol), paraformaldehyde (0.013 g, 0.44 mmol) and NaCNBH3 (0.014 g, 0.22 mmol) in 1 mL glacial acetic acid to afford 0.014 g (93%) of (3^)-3-ethyl-3,4-dihydro-8-isopropoxy-4-methyl-10-(trifluoromethyl)-2Ar- [1.4)o.Kazmo| 2,3-fjqumolme, of sufficient purity as to be used directly in the next reaction. Rf 0.5 (9:1 hexane:EtOAc); 'H NMR (400 MHz, CDC13) 5 7.44 (d, 1H. .7- 9.0), 7.20 (d. 1H, J = 9.0), ".'.18 (s, 1H), 5.48 (septet, 1H, /= 6.2), 4.29 (dd, ABX\ 1H, J= 10.7, 2.5), 4.02 (dd, .±BX, 1H,./- 10.7, 2.7), 3.21-3.16 (m, 1H), 3.03 (s, 3H), 1.74-1.56 (m, 2H), 1.39 (d, ?H,,/ - 6.2), 1.37 (d, 3H, ./= 6.2), 0.99 (t. 3H. .7= 7.5). (3^)-3-Ethv]-2.3,4,7-tetrahvdro-4-methyl-lO-(trifluoromethvl)-8/y- Lj .4ioxazmo| 2.3-/]quiHQlm-8-one (Compound 108. Structure 11 of Scheme II, where R'. R;'. R"1. R\ •- II, R2 -- iriiluorornethvi. R° = Et, R13 = CHi): Compound J08 was prepared according to General Method 4 (EXAMPLE 1) from (3^)-3-ethyl-3,4-dihydro-8- isopropoxy-4-raethyl-10-(trifiuoromethyl)-2flr-[l,4]oxazino[2,3-/]qumolme (0.014 g, 0.039 minor) ;n cone. HC1 (0.5 mL) in AcOH (1.0 mL) heated at 90°C to afford 10 mg (S3u/o) of Compound 108, a yellow solid. Rf 0.6 (9:1 CH2Cl2:MeOH); JH NMR (400 MHz. CDCh) 5 12.53 (broad s, 1H), 7.13 (s, 1H), 7.01 (s, 2H), 4.29 (d±ASX, 11LJ = 10.", 2.5)r 4.(.)5 (dd, ABX, 1H. J= 10.7, 2.7), 3.20-3.14 (m, 1H), 2.98 (s, 3H), 1.74-1.52 (m,2H). 0.98 (t, 3H, .7= 7.5). 53 EXAMPLE 9 (3)-3.4-Diethv^2.3.4.7-tetrahvdro-lQ-(trifluoromethvlV8F-fl.41oxazmor2.3-/1quinolin- S-one (Compound 109. Structure 11 of Scheme II. where R1, R3. R4. R5. = H. R2 = trilluoromethyl. R6 = Et. R13 = C&CBh) iMJb. 3.4-DiethyI-3.4-dihydro-8-isopropoxy-10-(trifJuoromethvl)-2//'- f l,4)oxazino|23-/lquinoline ('Structure 10 of Scheme II. where R'. R3, R4, R5. = H, R~ = IniluoromethvJ. R" -= Et. Ri3 = CH^CHQ: A solution of (3^)-3-ethyl-3.4-dihydro-8- isopropoxy-10~(tntiuoromethyl)-2#-[l,4]oxazino[2,3-/jquinolme (0.020 g, 0.059 mmol), excess acetic anhydride (ca. 0.5 mL) and excess triethylamine (ca. 0.5 mL) in THF was heated at 50°C for 24 h. The reaction mixture was poured into 25 mL water and extracted with EtOAc (2 x 25 mL). The extracts were washed sequentially with 25 mL portions of saturated NaHCCh, 0.1 N HC1 and bnne, dried over MgSO4, filtered and concentrated to afford 0.018 g of a yellow oil. This crude material was dissolved in 1.5 mL MTBE, transferred to a slurry of LAH (0.003 g) in 1.5 mL MTBE and heated to reflux for 20 h. The reaction mixture was poured into water (25 mL) and extracted with diethyl ether (2 x 25 mL). The extracts were washed with brine (25 mL), dried over MgSC>4, filtered and concentrated to 0.013 g yellow oil. Column chromatography (5-10% EtOAc in hexane gradient) afforded 4 mg (1 8%) of (3/?)-3,4-diethyl-3,4-dihydro-8-isopropoxy-10- (tnf]uoromethyl)-2/:/-[l,4]oxazino[2,3-/]quinoline as a yellow oil. Rf 0.7 (9:1 hexane:EtOAc); !H NMR (400 MHz, CDC13) 5 7.43 (d, 1H, J= 9.0), 7.26 (d, I H , J = 9.0). 7.17 (s. 1 H), 5.47 (septet, 1IL J= 6.2), 4.30 (dd, ABX, 1H, J= 10.4, 2.1), 3.83 (dd, ABX. 1IL J- 10.5; 2.6), 3.56-3.48 (m, 1H), 3.37-3.28 (m, 1H), 3.25-3.19 (m, 1H), 1.65- 1.55 (m, 2H). 1.39 (d, 3H, J= 6.2), 1.37 (d, 3H, J= 6.2), 1.20 (t, 3H, J= 7.1), 0.98 (t, 3H, ./ = 7.4V (3^)-3,4-Diethvl-2.3.4,7-tetrahydro-10-(trifluoromethyl)-8Ar-ri.41oxazinor2.3- (Compound 109. Structure 11 of Scheme II. where R'. RJ. R' . R3. = H. R'_- trifluoromethyl. R° = Et. Rb = CHoCHi): Compound 1 09 was prepared according to General Method 4 (EXAMPLE 1) from (3^)-3,4-diethyl-3,4-dihydro-8-isopropoxy-10- (tnfluorometlwl )-2/f-['l,4]oxazino[2,3:/]quinoline (O.OOS g; 0.022 mmol) in cone. HC1 (O.i mL) and AcOH (1.0 mL) heated at 90°C to afford 6 mg (86%) of Compound 109, a yellow solid. Rt 0.6 (9:1 CH2Cl2;MeQH); !H N3VIR (400 MHz, CDC13) 5 12.43 (broad s, 1H), 7.13 (s, 1H), 7.08 (d, 1H, J = 9.0), ), 7.01 (d, 1H, J= 9.0), 4.29 (dd, ABX, 1H, J= 10.5, 1.9), 3.85 (dd,AJBX, !H,-y.= 10.6, 2.6), 3.50-3.41 (m, 1H), 3.32-3.23 (m, 1H), 3.25- 3.16(m, 1H), 1.65-1.51 (m, 2H), 1.18 (t, 3H,J= 7.1), 0.97 (t, 3H, J= 7.5). EXAMPLE 10 LE thvi -2.3,4,7-tetrahvdro-4-(2.2,2-trifluoroethvl)-10-(trif]uoromethyl)-8^- 1 1 :4|oxazmgi 2.3-/1giLmplm-8-one (Compound 110, Structure 11 of Scheme II. where R , Sij^JRlt H- R' - trifluoromethvl R6 = Et. R13 = QfoCFQ This compound was prepared according to General Method 5 (EXAMPLE 2) from (3yO-3-ethyl-3,4-dihydro-8-isopropoxy-10-(tiifluorometliyl)-2//-[l,4]oxazino[2.3- /Iquinoline ( i).0()8 g, 0.024 mmol), NaCNBH3 (0.007 g, 0.1 18 mmol) and tnfluoroacetuldehyde ethyl hemiacetal (0.02S mL, 0.235 mmol) in TFA (0.8 mL) to afford U. 0 1 1 g o f ( 3 R)- 3 -ethyl-3 ,4-dihydro-8-isopropoxy-4-(2,2,2-trifluoroethyl)- 1 0- (tnfluoromethyD-2W-[l,4]oxazmo[2,3^/]quinoline, a brown-red solid. This matenal (0.01 7g) was earned on according to General Method 4 (EXAMPLE 1) by treatment with cone. HC1 (0.3 mL) in AcOH (0.6 mL) and heated at 95°C for 2 h to afford 0.006 g (67% ior the 1 steps) of Compound 110, a yellow solid. Rr0.4 (9:1 CH2Cl2;MeOH); ]H NMR (400 MHz, CDC13) S 12.47 (broad s, 1H), 7.15 (s, 1H), 7.14 (d, 1H, J= 8.9), 7.02 (d, 1H, J •-•• S.9). 4.38 id, 1 H..;= 10.9), 3.98 (dd, lH../= 10.8,2.4) 3.93-3.65 (m, 2H). 3.27-3.22 (m, 1H), 1.6.S-1.5l(m, 2H), 0.98 (t, 3H, J= 7.5). EXAMPLE 11 (3-/?)-4-(2-Chloro-2.2-difluoroethvl)-3-ethvl-23.4,7-tetrahvdro-lQ-(tnfluoromethylV8/:/- i r1.4joxaziaoj2.3-/]_quinolin-8-one (Compound 111, Structure 11 of Scheme II., where R1. R :. R4. R3. = H R2 = tnfluoromethvl R6 = Et, R13 = CH2CC1FZ) (3A!)-4ri2rChlQ.ro.-2.2-difluoroethyD-3-ethyl-3.4-dihydro-S-isgprQpoxy-lQ- (1nfluQromethyn-2J:/-[T,4]oxazinof2,3-/1quinolme (Structure 10 of Scheme II, where R'. BLR-l-ElR . R8 = H. R2 = trifluoromethvl R6 = Et, R13 = CH^CClFo]: This compound was prepared according to General Method 6 (EXAMPLE 3) from (3^)-3-ethyl-3,4- aihydro-8-isopropoxy-10-(trifluoromethyI)-2^f-[lJ4]oxazino[2,3-/]quinoline (22 mg, 0.06 mmol) and N-aBJELi pellets (large excess, >10 equiv) in 4 mL chlorodifluoroacetic acid (0.02 M) stirred at rt for 12 h, to afford 17 mg (61%) of (3£)-4~(2-chloro-2.2- difluoroethyJ)-3-ethy]-3,4-dihydro-S-isopropoxy-10-(trif]uoromethyl)-2j1:/'- [ 1,4]oxazino| 2_3:/]quinoline. 'H NMR (500 MHz, .GDC13) 7.44 (d, IH, J = 9.3), 7.32 (d, J = 1 H, C'.3X 7.21 (s. IH), 5.50 (m, IH), 4.39 (dd, IH, J = 10.7, 1.5), 4.09 (m, IH), 3.99 (dd, IH, J = 10.7. 2.4), 3.92 (m, IH), 3.33 (m, IH), 1.6 (m, 2H), 1.39 (d, 3H, J = 6.3), 1.38 (d, 311 J - 6.3), 0.09 (t, 3H, J = 7.3). f3J?)-4-i2-Chloro-2.2-difluoroethvlV3-ethvl-2.3.4J-tetrahydro-10- (tiT.niiQ_rQiTi_ethvl)-8//-ri14]Qxazino[2,3-/]quinolin-8-one (Compound 11]., Structure 11 of SchemeJJ^toejV^3, R4. R5, ~ H, R2 = trifluoromethvl. R6 = Et, R13 = CH^CClFg): Compound 1 1 ] was prepared according to General Method 4 (EXAMPLE 1) from (2>R)-4- (2-chloro-2,2 -difluoroethyl)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2/-/- [l,4]oxazino 2,3-/]qumolme (17 mg. 0.03 mmol) in 1 mL acetic acid and 1 mL concentrated HC1 heated at 90°C for 4 h to afford 8 mg (53%) of Compound 111, after punfication by flash chromatography (3:1 hexanesrEtOAc to 1:1 hexanes:EtOAc. gradient elution). 1H NMR (500 MHz, CDC13) 12.54 (bs, IH), 7.19 (d, IH, J = 8.8), 7.15 (s, IH), 7.03 (d, 1 H, .1 - 8.8), 4.39 (d, IH, J = 10.7), 4.06 (m, IH), 4.01 (dd, IH, J = 10.3, 2.0), 3.86 (m. IB). 3.31 (m. IH), 1.59 (m, 2H), 0.98 (t 3H, J = 7.3). EXAMPLE 12 i3^)-4-('2,2rDi.fli!orQethy])-3-ethy]-2,3.4.7-tetrahvdro-10ri'trifIuorQmethyI)-8//- j 1.41oxazmp| 2.3-/1qumolin-8-one (Compound 112. Structure 11 of Scheme II. where R'. £:- R'1. R\.^ H. R: - trifluoromethyl. R° = Et. R13 = CHZCHFZ) Compound 112 was prepared according to General Method 6 (EXAMPLE 3) from (3A')-J-ethy]-.\4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2^'-[l,4]oxazino[2,3- /jqiiinoljTie (13 mg, 0.04 rrrrnol) and NaBH^ pellets (large excess, >10 equiv) in 3 mL dmuoroacetic acid (0.01 M) stirred at rt for 12 h, to afford S mg (53%) of (3J?)-4-(2.2- d]lluoroethyl)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2/-/- [1,4Joxazino[2.3-_/]quinoline. This material (8 mg, 0.02 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 1.5 mL acetic acid and 1.5 mL concentrated H.C1 and heated at 90°C for 4 h to afford 4 mg (57 %) of Compound 112, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes:EtOAc, gradient elution). JH NMR (500 MHz, CDC13) 12.19 (bs, IH), 7.14 (s. IH), 7.09 (d, IH, J = 8.8), 6.99 (d, 1H, J = 9.3), 5.95 (m, 1H), 4.34 (dd, 1H, J = 10.7, 1.5), 3.98 (dd, 1H, J = 10.7, 2.4), 3.70 (m, 1H), 3.58 (m, 1H), 3.25 (m, 1H), 1.58 (m, 2H)/0.98 (t, 3H, J = 7.3): EXAMPLE 13 (3^)-3-Ethvl-2.3,4,7-tetralivdro-4-propvl-10-(tnfluoromethvl)-8J/:/'-ri.4]oxazino[2.3- /Igamolin-S-oQe (Compound 113. Structure 11 of Scheme II, where R1. R3, R4, R3, = H, R2 = influorornelhvl. R6 = Et, R13 = (3/?)-4-Allvl-3-ethvl-3,4-dihvdro-8-isopropoxv-10-ftrifluoromethvl)-2//- [ 1 .4|oxazmo[2.3:/1quinoline: To a suspension of (3J?)-3-ethyl-3,4-dihydro-8-isopropoxy- 10-(trifluorometliyl)-2#-[l,4]oxazmo[2,3-/]quinoline (0.250 g, 0.734 mmol) andK2CO3 (0.507 g, 3.67 mmol) in 3 mL DMF was added ally! bromide (0.636 mL, 7.34 mmol) and the reaction mixture was heated to 50°C for 4 h. The reaction mixture was poured into 40 mL water anu extracted with EtOAc (2 x 30 mL). The extracts were washed with 40 mL each water and brine, dried over MgSCU, filtered and concentrated to a yellow oil. Column chromatography (5-10 % EtOAc in hexane gradient) afforded 0.24 g (86% yield) of ('3A')-4-allyi-3-ethyl-3,4-dihydro-S-isopropoxy-10-(tiifluoromethyl)-2/ir- [ 1 ,41oxazmo| 2,3:/]qumoline. a yellow oil. Rf 0.6 (9: 1 hexane:EtOAc); 'H NMR (400 MH:-.. CDC1-, i 5 7.41 (d, 1H,. 7= 9.0), 7.21 (d, 1H, 7=9.0), 7.18 (s, 1H), 5.96-5.85 (m, I K ) . ; . . 47 (septet, 1H, .7=6.1). 5.25 (dd. ABX, 1H./=17.1, 1.1), 5.20 (d, 1H,.7= 10.1), 4.3 1 (dd, ABX.. \ H, J= 10.7, 2.2), 4.03 (dd, ABX, 1H, J= 16.8, 5.0), 3.95-3.89 (m. 2H), 3.27-3.22 (m. 1H), 1.69-1.59 (m, 2H), 1.38 (d, 3H,/= 6.1), 1.37 (d, 3H, J= 6.1), 0.97 (t, 311 ./- 7.5). n,,4]oxazmo|2_3-/]quinoline: To a solution of (3^)-4-allyl-3-ethyl-3,4-dihydro-8- isopropoxy-I ')-(trifluoromethyl)-2fl'-[l,4]oxazmo[2,3-/]quinoline (0.24 g, 0.63 mmol) and 0. mL Et;,N in 3 mL EtOAc was added 10% Pd on carbon (0.08 g) and the mixture was vigorously stirred under H? atmosphere for 1 h. The reaction mixture was filtered through Celite and concentrated to give 0.23 g (96% yield) of (3^)-3-ethyl-3,4-dihydro-8- isopropoxy-4-propyl-l 0-(tnfluoromethyl)-2Lr-[l,4]oxazino[2,3-/]quinoline, a yellow oil. Rr 0.7 (9: 1 hexane:EtOAc); lll NMR (400 MHz, CDC13) 6 7.41 (d, 1H, J= 9.1), 7.22 (d, 1H.J=9.1). 7.17(s, 1H), 5.47 (septet. 1H, J= 6.2), 4.30 (dd,ABX, 1H,J= 10.5, 1.6), 3.86 (dd, ABX, 1H. J= 10.5, 2.5), 3.47-3.35 (m, 1H), 3.23-3.11 (m, 2H), 1.70-1.55 (m, 411).. 1.38 (d, 31-L -7 = 6.2), 1.37 (d, 3H, J= 6.2), 1.02-0.91 (m, 6H). - • ' LM1-A -Bthvl-23.4.?-teirahvdrQ-4-propvl-lQ-(tnfluoromethyl)-8/7- [L4|oxazmQ^2,3-/:lqumolin-8-one (Compound 113, Structure 11 of Scheme II, where R.1, R;\ R4. R:i. = 1L R2 = trifluoromethvl. R6 = Et R13 = CHZCHZCH;Q: Compound 113 was prepared according to General Method 4 (EXAMPLE 1) from (3/?)-3-ethyl-3,4-dihydro-8- isopropoxy-4-propyl-10-(trifluoromethyl)-2//'-[l,4]oxazino[2,3-/lqumoline (0.23 g, 0.60 nimol) in cone. HC1 (2.0 mL) and AcOH (4.0 mL) heated at 95°C to afford 0.1S g (88%) of Compound 113, a yellow solid. Rf 0.6 (9:1 CH2Cl2;MeOH); ]H JNTVIR (400 MHz, CDCh) 8 11.79 (broad s, 1H), 7.11 (s, 1H), 7.03 (d, 1H, J= 8.9), ), 6.93 (d, 1H, J= 8.8), 4.30 (dd, ABA', 1H, J = 10.8, 2.0), 3.89 (dd, ABX, 1H, J= 10.6, 2.7), 3.39-3.29 (m, 1H), 3.21-3.16 (m. 1H), 3.16-3.06 (m, 1H), 1.69-1.51 (m, 4H), 1.01-0.93 (m, 6H). EXAMPLE 14 (l^hrtilljvi; ,3-cthvl-2.3.4.7-tetrahvdro-lQ-(trifluoromethvl)-8Ar-n.41oxazmor2.3- /luiiinolin-8-uno (Compound 114, Structure 11 of Scheme II. where R\ RJ. R4. R3. =H. Elf: Trifluoromethvl R6 - Et. R13 = -CHZCH=CH2) i.'ornpound 114 was prepared by General Method 4 (EXAMPLE 1) from (3jf?)-4- ail yl-3-erhyk ',4-dihydro-S-isopropoxy- 10-(tnfluoromethyl)-2/7-fl,4]oxazino[2,3- /]quinoline (EXAMPLE 13) (0.016 g, 0.041 mmol) in cone. HC1 (1 mL) heated at 75°C to afford 13 trig (93%) of Compound 114, a yellow solid. Rf 0.5 (9:1 CH2Cl2;MeOH); !H NMR (400 MHz, CDC13) 5 12.52 (broad s, 1H), 7.12 (s, 1H), 7.04 (d, 1H, /= S.9); 6.99 (d, 1 H, ./= S.'-'), 5.91-5.81 (m, 1H), 5.26-5.18 (m, 2H), 4.31 (dd, ABX\ 1H, J= 10.6, 2.2), 4.00-3.92 (m. 2H), 3.87 (dd, ABX, Hi, ,/= 16.S, 5.1), 3.25-3.20 (m, 1H), 1.65-1.51 (m, 2H). 0.96 (!,:-:Hr ,7=7.4). EXAMPLE 15 O^):Mihyl- ,:'..3,4.7-tefrahvdro-4-isobutvl-10-(tnfluoromethvl)-S//-ri.41oxazinor2.3- /1quinolin-S-otie (Compound 115. Structure 11 of Scheme II. where R1. RJ. R4. R3. R7, R8 = H. R: = trifluoromethvl. Rfa = Et. R13 = CH2CH(CHOZ) L-L^L: 3 -Ethyl-3.4rdihydrp-8-isopropoxy-4-methallyl-lQ-(trifluoromethyl')-2/^'- [1.4]Qxazino[2,3-:/]quinpline: To a suspension of (^?)-3-ethyl-3,4-dihydro-S-isopropoxy- 10-(tnfluorom.ethyl)-2flr-[ls4]oxazino[2,3-/|quinoline (0.020 g, 0.059 mmol) andK2CO3 (0.041 g, 0.295 mmol) in 1 ml DMF was added methallyl bromide (0.077 mL, 0.767 mmol) and the reaction mixture was heated to 50°C for 16 h. The reaction mixture was poured into _' 5 mL water and extracted with EtOAc (2 x 25 mL). The extracts were washed \vith 15 ml each water and bnne, dried over MgSCU, filtered and concentrated to a yellow oil. Column chromatography (5-10% EtOAc in hexane gradient) gave 0.020 g (87%) of(./v)-3-ethyl-3,4-dilwdro-S-isopropoxy-4-methallyl-10-(trifluoromethyl)-2//- [ 1.4 joxazino[2,3:/]qumoline, a yellow oil. Rf 0.7 (9:1 hexane:EtOAc); 'H NMR (400 MHz,, CT)CK« 5 7,39 (d, 1H, ./ = 9.0), 7.18 (s, 1H), 7.12 (d, 1H, J= 9.0), 5.47 (septet, 1H, J- 6.2), 4.91 (S, 2H), 4.33 (dd, ABX, 1H, J= 10.6, 2.0), 3.96 (dd, ABX, 1H, J= 10.7, 2.6), 3,86 (d, Hi,,/ = 17.0), 3.80 (d, 1R ,7 = 17.0), 3.25-3.20 (m, 1H), 1.79'(s, 3H), 1.65-1.59 (m, 211), 1.38 (d, 3H, J= 6.1), 1.37 (d, 3H, J= 6.1), 0.97 (t, 3H, J= 7.5). (3 R j^ ~EthyKL3 A7_-tetrahvdro-4-isobutyl-10-(trifluoromethyl)-8/f- | ],4joxazinp[2^3-/lquinolin-8-one (Compound 115. Structure 11 of Scheme II. where R1, R\ R4. R\ - H. R- •= tnfluoromethvl. Rb = Et. Ri: = CHkCHCHVM: To a solution of (^)- 3-ethyl-3,4-dihydro-8-isopropoxy-4-methallyl-10-(trifluoromethyl)-2^/'-[l,4]oxazino[2,3- /jquinoline ((;.0 i 0 g, 0,025 mmol m 1.5 mL EtOAc and 0.1 mL Et3N was added 10% Pd on carbon (O.oOo g) and the mixture was vigorously stirred under HT atmosphere for 1 h. The reaction mixture was filtered through Celite and concentrated to afford 0.010 g (100% yield) of (/\)'-3-et.hyl-3,4-dihydro-4-isobutyl-8-isopropoxy-10~(tnfluoromethyl)-2^7- f 1.4 joxazmol 2,3:/]qumoline, a yellow oil. This material (0.010 g, 0.025 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with cone. HCI (0.5 ml. i m AcOH (1.0 mL) and heated at 95°C to afford Compound 115 (0.008 g, 89% yield) as a yellow solid. Rf 0.5 (9:1 CH2Cl2:MeOH); !H NMR (400 MHz, CDC13) 5 11.81 (broad s. Hi) 7.1 1 (s, 1H), 7.00 (d, 1H, J = 9.0), 6.92 (d, 1H, J= 9.0), 4.33 (dd, ABX. 1H, ,/ - 10.4. ! .2), 3.98 (dd, ABX. 1R .7= 10.4, 2.3), 3.23 (dd, ABX, 1H, 7= 14.5, 4.8), 3.15- 3 10(in, \H). 2.80 (dd, ABX, 1H, /= 14.5, 9.8), 2.07-1.97 (m, 1H), 1.62-1.49 (m, 2H), 1.01 (d, 3H,.; = 6.5), 0.98-0.92 (m, 6H). EXAMPLE 16 (-)-2.3.4J-Tetrahvdro-3-propvl-10-(trifluorornethvl)-8g-rL41oxa2ino[2.3-/lquinoliB-8- one (Compound 116. Structure 9 of Scheme II. where R1. R3. R4, R5. R7. R8 = H. R2 = tnfluoromethvl. R" = /?-Pr) (i Hi: Bromo-5-[('2'-?-butoxvcarbonvlaniino)-l'-pentoxv1-2-isoprppoxy-4- (tnfkiQromethyl iqumoline (Structure 7 of Scheme II, where R1. RJ. R',.RS. R'. Rs = H. R2 — trifluoromethyl, R6 = 77 -Pr): This compounds was prepared according to General Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4- (tnfluoromethyl)quinoline (0.5 g, 1.43 mmol, 1 equiv), (±)-2-(7V-z'-butoxycarbonylamino)- 1 -pen tan ol (470 mg, 2.28 mol. 1.6 equiv), triphenylphosphine (600 mg, 2.28 mol, 1.6 equiv). diisopropyl azodicarboxylate (0.45 ml, 2.28 mol, 1.6 equiv) and 7vmethylmorpholine (0.6 ml, 10 equiv) in dry THF (14 ml, 0.1 M) to afford 483 mg (63%) or(±)-6--bromo-5-[(2'-t-butoxycarbonylamino)-l'-pentoxy]-2-isopropoxy-4- (tniluoroTnethyl)quinoline, a white foam, after column chromatography (100% hexanes to 9:1 hexanes: B.O Ac, gradient elution). 'H NMR (500 MHz, CDC13) 5 7.8 (d, /= S.8, l i d ) . 7.55 i d , . / -8 8, 1H). 7.3 (s, Iff), 5.52 (m, 1H), 4.79 (bs, Iff), 4.12 (m, 1H), 3.99 (m, 2H>. 1.7 (rn. 1 H ) : 1.63 (m. 1 HX 1 .46 (s, QH), 1.41 (d. J= 5.9, 6H), 0.98 (t, J= 7.3. 3H). i.r):_o-Bronio-5-(2'rammo-l '-pentoxy)-2-isopropoxy-4-('trifluoromethvnquinoline : Tins compound was prepared according to General Method 2 (EXAMPLE 1 ) from (+)-6- bromo-5 -| (2'-;-butox ycarbonylammo j-1 '-pentoxyJ-2-isopropoxy-4- (trifluoromethyl)quinoline (480 mg, 0.9 mmol) in 5 mL CH2C12 and 5 mL TFA (0.09 M) stirred al it for 2 h to afford 280 mg (12%) of (±)-6-bromo-5-(2'-amino-r-pentoxy)-2- isopropoxy-4-(tnfluoromethyl)quinoline after column cllromatography (9:1 hexanes: ethyl acetate to 1 : 1 hex anes: ethyl acetate, gradient elution). [E NMR (500 MHz, CDC13) 5 7. SI (d,- S.S, IK), 7.55 (d,y=S.S, 1H), 7.30 (s, 1H), 5.53 (m, 1H), 3.S6 (m. 2H), 3.45 (m, 111), 1 .42 (d, ./ =-• 5.9, 3H), 1.41 (d,J=5.9, 3H), 1.39 (m, 4H), 0.95 (t, /= 6.8, 3H). l-l 0-(trifluoromethvl)-2/f-f 1 .4]oxazinor2.3- uie ('Structure S of Scheme II. where R1. R3. R4. R5. = H. R2 = tnfluoromethvl. R6 fjPrj: This compound was prepared according to General Method 3 (EXAMPLE 1) from i±)-t)-bri)ino-5'-(2'-amino-r-pentoxy)-2-isopropoxy-4-(trifluoromethyl)quinoline (280 nig, 0.64 mol, 1 equiv), (=)-2.2'-bis(diphenylphosphmo)-l,r-bmaphthyl (16 mg, 60 4 raol %), ?d:(dbaj3 (11.8 mg, 2 mol%), sodium /-butoxide (87 mg, 0.9 mmol, 1.4 equiv) in 5 mL toluene (0.2 M) heated at 90°C for 12 h to afford 172 mg (75%) of (±)-3,4- : dihydro-8-isor)ropoxy-3-propyl-10-(trifluoromethyl)-2/J-[1.4]oxazino[2,3-/lqu.inoline after flash chromatography (100% hexanes to 4:1 kexanes:EtOAc). !H NMR (500 MHz, CDrh)67.3t>(d. ,/-8.8, 1H), ~ IS(s, 1H), 7.03 (d, ./= 8.8, 1H), 5.47 (m, 1H), 4.35 (dd, ./- id7 2.9, 11-f), 3. 85 (dd, J= 10.7, 7.6, 1H), 3.81 (s, 1H), 3.52 (m, 1H), 1.51 (m, 4H), l . : X ( d , . / • = 5 0;6H), (. 00 (t, ,7=6.6, 3H). (±)-2..>.4.7-'retrahvdro-3-prQpyl-10-(tnfluoromethvl)-8J:/-ri.4'|oxa2mQ[23- /Igumoinbg-one (Compound 116. Structure 9 of Scheme II, where R1. R". R4,.R5. =H. R2 ~- trtfltipromethyl, Rb = 7?-Pr): Compound 116 was prepared according to General Method 4 (EXAMPL1; 1 ) from (±)-3,4-dihydro-8-isopropoxy-3-propyl-10-(trifluoromethyl)-2^'- ( 1.4'|oxazino[ 2,3-/]quinoline (10 mg, 0.03 mmol) in 1 mL 1:1 acetic acidtconcentrated HC1 (0.03 M) heated at 90°C lor 3 h to afford 8 mg (97%) of Compound 116. JH NMR (500 V1H/., CDC1V. 6 11.55(bs, 1H), 7.11 (s, 1H), 6.91 (d,J=8.8, 1H), 6.86 (d, .7= 8.8, 1H), 4. is (dd../- lO 25, 2.93, 11-1), 3.85 (dd, J= 10.7, 7.8, 1H), 3.73 (bs, 1H), 3.47 (m, 1H), ! 4" (m.4HK I -00 (t,./-6.6, 3H). EXAMPLEJL7 L:::);IAAZ::JJ^ /Iqujnojin-jj-cine (CoinpouTid 1 17. Structure 11 of Scheme II. where R'. R'. R\R'\ = H. (Compound 1.17 was prepared according to General Method 5 (EXAMPLE 2) from (±)-3,4-dihydro-S-Lsopropoxy-3-propyl-10-(trifluoromethyl)-2//-[l,4]oxazino[2,3- / j q u i n o i i n e ( 1 8 rng, 0.05 mmol), 37% aqueous formaldehyde (0.01 mL, 0.3 mmol, 5 eq), sodium cyanoborohydnde (16 mg, 0.3 mmol, 5 eq) in 1 mL acetic acid (0.05 M) stirred at n for 12 h to afford 7 mg of (3/?/'Srj-3,4-dihydro-8-isopropoxy-4-methyl-3-propyHO- (tnrluoromethyl )-2.ftr-[1.4]oxazino[2.3-/lqumoline. This material (7 mg, 0.02 mmol) was earned on according to General M.ethod 4 (EXAMPLE 1) by treatment with 4 mL of a 1 :1 acetic acuLconcentrated HC1 (5 mM) and heated at 90°C for 6 h to afford 5 mg (83%) of Compound 1 !7 after column chroraatography (3 : 1 hexanes:EtOAc to 1:1 hexanes :EtO Ac, gradient eluuons. XH NMR (500 MHz, CDC13) 5 10.83 (bs, 1H), 7.11 (s, 1H), 6.99 (d, ./- S.8, 1H), 6.S7 (d,J= S.S, 1H), 4.28 (dd,y= 10.7, 2.2, 1H), 4.07 (dd,./= 10.7, 2.4, 1H), 3.24 (m, IH), 2.97 (s, 3H) 1.48 (m, 4H), 0.96 (t,/= 7.3, 3H). EXAMPLE 18 2.3.4,7-Terrahvdro-3-propyl-10-ftrifluoromethvlVS//'-!' 1.4'|oxazinor2.3- /Iquinolin-S-one (Compound 118. Structure 11 of Scheme II. where R1. R3. R4. R5. = H, •R- =• tnfluoi-omethvl, R6 = »-Pr, R13 = CHgCEh) Compound 118 was prepared according to General Method 6 (EXAMPLE 3) from (±)-3,4-dihydro-8-isopropoxy-3-propyl-10-(trifluoromethyl)-2//-[l,4]oxazino[2.3- /Jqumoline (. 11 mg, 0.03 mmol) and NaBHU pellets (>10 equiv) in 1 mL acetic acid (0.03 M) stirred at rt for 12 h to afford 9 mg of (±)-4-ethyl-3,4-dihydro-S-isopropoxy-3-propyl~ 10-(tnfluoromethyl)-2fy-[l,4]oxazrno[2,3-/jquinoline. This matenal (9 mg, 0.02 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 4 mL of 1 : 1 acetic acid:concentrated HC1 (5.9 mM) and heated at 90°C for 6 h to afford 6 mg (75%) of Compound 118 after flash chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:.EtOAc, gradient elution). 'H: NMR (500 MHz, CDC13) 5 11.91 (bs. 1H), 7.12 (s. 1 H), 7.07 ( d , . / = S.S, 1H), 6.96 (d, J= S.S. 1H), 4.27 (dd, J= 10.3, 2.0, 1H), 3.90 (dd, J=-- [03. 2 7, 1H). 7.44 (m, Iff), 3.27 (m, 111), 3.26 (m, 1H), 1.52 (m, 2H), 1.41 (m, 2H), 1.18 n.,/- ' . I . ni) 0.94 (\.J= 7.3, 3H). EXAMPLE 19 i± 1-2/3 i4.^Tetrahydrp-3-prQpyl-4-(2.2.2-trifluoroethyl)-10-(trifluorome f L41oxazmp|2.3-/]qumolin-S-one (Compound 119, Structure 11 of Scheme 1L where R!. Si..El R\/- H. R2 = tnfluoromethyl, R6 = ;;-Pr. R13 = CH2CFQ Compound 119 was prepared according to General Method 6 (EXAMPLE 3) from i±)-3,4 •dihYdro-8-Lsopropoxy-3-propyl-10-(trifluoromethyl)-2/jT-[l,4]oxazmo[2,3- /Iquinoline (16 mg, 0.05 mmol) andNaBKU pellets (>10 equiv) in 11 mL trifluoroacetic acid (0.04 M.) stirred at rt for 12 h to afford 27 mg of (±)-3,4-dihydro-3-propyl-4-(2,2,2- frifluoroethyl)-! 0-(trifluoromethyl)-S/7-[l,4]oxazino[2,3-/]quinoline. This matenal (27 ing. 0.06 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 1:1 acetic acid:concentrated HC1 (0.03M) and heated at 90°C for 6 h to afford i 1 mg (50% for the 2 steps) of Compound 119 after flash chromatography (3:1 hexanes:EtGA.c to 1 : 1 hexanes:EtOAc, gradient elution). *H NMR (500 MHz, CDC13) 5 11.78 (bs, IH), 7.14 (s, IH), 7.07 (d,J= 8.8, IH), 6.95 (d,/ = 8.8, IH), 4.35 (dd,'/= 10.7, 1.5, IH), 3.99 (dd,J= 10.7, 2.4, IH), 3.83 (m, IH), 3.72 (m, IH), 3.32 (m, IH), 1.51 (rn, 2H), ! .42 (m, 211), 0.93 (t. 7= 7.3, 3H). EXAMPLE 20 L?/il:~_-_l-.ri-..Z::-i etra}wdro-3-isoiiropvir10-(tnfluoromethv{)-8g-ri,4]gxazino[2.3-1qumolm- S-one (Compound 120, Structure 9 of Scheme II. where R1. R3. R4, R5. = H. R2 = tTilluoromethvl, R' = i-Pr) (2'/i)ro-liromo-5-|Y2'-/-butoxvcai-bonvlamino)-3'-methvl-r-pentoxv]-2- isoprQpoxv-4--(trifliioromethvl)quinoline (Structure 7 of Scheme II, where R1. R3, R4. R5. -= IL PX - tnfluoromethyl, Rb - (-Pr): This compound was prepared according to General Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4- (tnfluoromethyDquinoline (0.755 g, 2.16 mmol), (R)-N-t-Boc valinol (0.701 g, 3.45 mmol'), tnpheaylphospm'ne (0.905 g, 3.45 mmol), DIAD (0.679 mL. 3.45 mmol) and A7- methyhnorpholine (1 5 niL) in THE (20 mL) to afford 0.79 g (68%) of (2'^)-6-bromo-5- l(2'-/-but.oxyc;irbonylamino)-3'-methyl-r-pentoxy]-2-isopropoxy-4- (tnlluoroinetlivDquinolme, a tan solid. Rf 0.4 (9:1 hexane:EtOAc); 1H NMR (400 MHz. CDCl-oo 7.""(a, IH,./- 9.0), 7.55 (d, IH, ./= 9.0), 7.30 (s, IH), 5.52 (septet, IH. ,/ = 6.2\ 4.81-4.7-^ (m, IH), 4.14-3.90 (m, 3H), 2.15-2.01 (m, IH), 1.46 (s. 9H), 1.41 (d, 6H.,/ =-- 0.2). 0»9-0 9o (m, 6H). Q R)-3,4_-Dihvdro-8-isoproppxy-3-isopropyl-l 0-(trifluoromethvlV2ffj 1.4loxazinof 2,3-/'jquinohne: This compound was prepared according to General Method 2 (EXAMPLE 1) from (2'/?)-6-bromo-5-[(2'-r-butoxycarbonylamino)-3'-methyl-rpenioxyj- 2-isopropoxy-4-(trifluoromethyl)quinoline (0.79 g, 1.5 mmo]) in CH2CE (10 mL) and TEA (10 ml.) to afford (2'J?')-6-bromo-5-(2'-ammo-3'-methyl-r-pentoxy)-2- isopropoxy-4-(trifluoromethyl)quinoline (0.52 g, 80% yield). This material (0.52 g, 1.2 mmol) was carried on according to General Method 3 (EXAMPLE 1) by treatment with Pd-i'dbah (0.021 g. 2 mol%), (+VBENAP (0.030 g, 4 mol%) and /-BuONa (0.15S g, 1.64 mmol) in toluene (7 mL) to afford 0.320 g (77%) of (3^?)-3,4-dihydro-S-isopropoxy-3- isopropyl-10-i, trifluoromethyl)-2//-[l,4]oxazino[2,3-_/]qmnoline. a yellow solid. Rf 0.4 (9:1 hexane:EtOAc): 'H NMR (400 MHz, CDC13) 5 7.36 (d, 1H: J = 8.7), 7.18 (s, IH), 7.04 (ci, 1H, /- S. 7), 5.47 (septet, 1H, J= 6.1), 4.36 (dd,ABX, lH,/= 10.6, 2.8), 3.97 (dd,AJ3X, 1H,J= 10.6, 7.5), 3.87 (broad s, Iff), 3.29-3.21 (m, Iff), 1.83-1.74 (m, 1H), 1 .38 (d, 6H, ,/ = 6.2), 1.06 (d, 3H, J= 6.8), 1.03 (d, 3H, J= 6.8). LMI 2.3?4.7-Tetrahydro-3-isopropyl-10-(tnfluoromethyl)-Sff-['l,41oxazmo[2,3- /lquinoljn-8 -one (Compound 120, Structure 9 of Scheme II. where R1. R". R . R3, =H. Compound 120 was prepared according to General Method 4 (EXAMPLE 1) from (.3/?)-3,4-(iihydro-8-isopropoxy-3-isopropyl-]0-(trifluoromethyl)-2^-[l,4]oxazmo[2.,3- /jqumolme (0.006 g, 0.017 mmol) in cone. HC1 (0.5 mL) and AcOH (1.0 mL) to afford Compound 320 (0.005 g, 100% yield), a yellow solid. Rf 0.4 (9:1 CH2Cl2:MeOH); 1E >MR (400 MHz, CDC13) 5 12.48 (broad s, 1H), 7.12 (s, 1H), 6.93 (s, 2H), 4.37 (dd, ABX, [ H. ,/=• 1 0.6, 2.8), 3.97 (dd. ABX, IE, J= 10.4, 7.5), 3.81 (broad s, 1H), 3.26-3.16 (m, Hi). 1.8.3-1.71 (m, 1H), 1.06 (d, 3H, J= 6.7), 1.03 (d, 3H,./= 6.7). EXAMPLE 21 ( 3/0:2 JAI:T^ rlqiiinolin-8-one (Compound 121, Structure 11 of Scheme II. Avhere R1. R'. R4. R'\ = H, R i_- . rn fluor. m Compound 121 was prepared according to General Method 5 (EXAMPLE 2) from (3A')-3,4-dil] vdro-8-isopropoxy-3-isopropyl-10-(trifluoromethyl)-2/:/'-[l,4]oxazmo[2,3- /jqumolme (0.010 g, 0.028 mmol) with paraformaldehyde (0.008 g, 0.280 mmol) and NaCNBIi-; (0.009 g, 0.-140 mmol) in AcOH (1 mL) to afford 0.009 g (90%) of (3A>3,4- dihydro-8-isopropoxy-3-isopropyl-4-methyl-10-(trifluoromethyl)-2H-[l.,4]oxazmo[2,3- /jqumolmt;. a yellow oil. This material (0.009 g, 0.025 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with cone. HC1 (0.5 mL) and AcOH (1 ml.) to afford 0.006 g (86%) of Compound 121 as a yellow solid. Rf 0.6 (9:1 CH:CkMeOH); 'H NMR (400 MHz, CDC13) 5 12.49 (broad s, 1H), 7.13 (s, 1H), 7.06 (d. 1 H . . / - S.9), 7.02 (d, 1H. .7 = 8.9), 4.43 (dd,^^ 1H, J= 10.9, 1.8), 3.86 (dd,A£X, 1H,/ - ]0.0;2.9), 3.03 (s. 3H). 2.93-2.88 (m. 1H), 2.02-1.91 (m, 1H), 0.99 (d, 3H, ,/= 6.9), 0.95 ici. 3H. ,/= 6.9). EXAMPLE 22 (3/?V4-Ethvl-2,3,4,7-tetrahvdro-3-isopropvl-10-(trifluoroniethviV8tf-ri,41oxazinor2.3- jQmimo]i]> 8 - ' me (Compound 122. Structure 11 of Scheme II, where R1, R3. R4. Rs, = H, R" - trifhioromethyl. R6 = z'Pr. R13 = CHsCHV) Compound 122 was prepared according to General Method 5 (EXAMPLE 2) from (3Av)-3,4--dihydro-S-isopropoxy-3-isopropyl--10-(tnfluoromethyl)-2//-[l,4]oxazino[2,3- /Jqumoline pO mg. 0.14 rnmol) and NaBH4 pellets (>10 equiv) in 2 mL acetic acid to afford 30 rag (ca. 60%) of (3^?)-4-ethyl-3,4-dihydro-8-isopropoxy-3-isopropyl-10- (trifluoromethy!)-2/^-[l,4]oxazino[2,3-/]quinoline. This material (30 mg, 0.08 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 4 mL of 1 : 1 acetic acid:concentrated HC1 (0.02M) heated at 90°C for 4 h to afford 1 5 mg (57%) of Compound '1 22, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1 : 1 hexanes:fitO.\c. gradient elution). ]H NMR (500 MHz, CDC13) 8 1 1.87 (bs, 1H), 7.13 (d, 7-0.3, ]J-n, 7.!2(s, lEl 6.96 (d. ./= 8.9, 1H), 4.49 (d,J= 10.8, IH), 3.69 (dd, J= 10.7, 2.1. IH). 3.4l»(rn; lH),3.24(m, 1 H), 2.SS (bd, 7= 7.9, IH) 1.83 (m, IH), 1.64 (t, ./= 7.1, 31-i), 0.->8 ( d , . / - 1 0.6: 3H), 0.96 (d,y= 10.6, 3H). EXAMPLE 23 .ll/iQii , 3_.4 . 7_ Tetrah^_dro-3-]Sopropyl-4-(2.2.2-trifluoroethvl)-10-(trifluoromet.hyl)-S/^- (Compound 123. Structure 11 of Scheme II, where R'. .E:LJ:1.^L::: M, R2 = trifluoromethvl R6 = i-Pr. R13 = Compound 123 was prepared according to General Method 3 (EXAMPLE 1) from (3V3,4-dilivdro-8-isopropoxy-3-isopropyl-10-(txifluoromethyl)-2//-[l,4]oxazino[2,3- Iqumoime (0.32 g, 0.90 mmol) wimNaBH4 (0.52 g, 14 mmol) mTFA (10 mL) to afford 0.39 g ( 100°/r>) of (3/i!)-3,4-dihydro-8-isopropoxy-3-isopropyl-4-(2,2,2-trifluoroethyl)-10- (tnfluoromethyr)-2jy-[l,4]oxazuio[2,3-/]quraoline, a yellow oil. This material (0.39 g, 0.90 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with cone. HC1 (3 mL) in AcOH (6 ml,) to afford 0.31 g (88%) of Compound 123, a yellow solid. Rr 0.3 1 19:1 CH2Cl2:MeOH); !H NMR (400 MHz, CDC13) 5 12.87 (broad sr IH), 7.20 i d . IH, 7-8.9). 7.15 (s, IH), 7.01 (d, IH, J= S.9), 4.58 (d, IH, 7= 10.8), 3.93-3.82 (m, 2HX 3.72-3.61 (m, 1H), 2.88 (d, 1H, J= 9.2), 1.81-1.74 (m, Iff), 1.00 (d, 3H, J = 6.2), 0.98 (d,3H,J = 6.2). ' ' ' ; ' ' EXAMPLE 24 i3/?)-4-(2-C]uoi-o-2.2-difluurQethvl)-2.3.4.7-tetrahvdro-3-isopropvl-10-(trifluoromethyn- 8fy-{'1.4jo,x:azii)o[2.3-/1quinolin-8-one (Compound 124. Structure 11 of Scheme II, where RlvJLLRlB!, " H. R2 = tnfluoromethvl R6 = f-Pr. R13 = CH2CC1F2) (3^)-4-(2-Chloro-2.2-difluoroethvlV3,4-dihvdro-8-isopropoxy-3-isopropyl-10- (trifluoromethvl)-2//-[1.41oxazmor2,3-/1quinoline (Structure 10 of Scheme II. where R1. R-. R4. R5. ^ H. R2 = trifluoromethvl. R6 = i-Pr, R13 = OfoCClF;): This compound was prepared according to General Method 6 (EXAMPLE 3) from (3AO- 4-(2-chloro-2,2- dinuoroethyi)-3.4-dihydro-8-isopropoxy-3-isopropyl-10-(trifluoromethy])-2//- [ l,4]oxazmo[2.3~/]quinoline (30 mg, 0.1 rrrmol) and NaBH4 pellets (large excess, >10 equiv) in 3 mL chlorodifluoroacetic acid (0.03 M) stirred at rt for 12 h. to afford 22 mg (:""•..') of (3A')-4-ethyl-3,4-dihydro-S-isopropoxy-3-methyl-10-(trifluoromethyl)-27;/- [1.4]oxazmo| 2.3-/]quinoline. 'H NMR (500 MHz. CDC13) 5 7.44 (d. J = 9.3. Hi), 7.30 (u. .1 - 'A3. 1 H). 7.21 (s, 1HX 5.98 (mr 1H), 5.49 (m, 1H), 4.55 (dd, J = 10.7, 2.4, Iff), 3.84 (d.i .1 - 10.7 2.4. Iff), 3.79 (m, Iff). 3.54 (m, Iff), 2.93 (m, Iff), 1.84 (m. Iff), 1.39 (d, J 6.3, 31-i). 1 .3,\ (d, J - 6.3, 3ff), i .00 (d, J - 9.8, 3H), 0.99 id, J = 9.S, 3H). (3A')-4-(2-Ch{Qro-2,2-difluoroethyl)-2,3,4,7-tetrahvdro-3-isopropvl-ia- (tnl]apjLMiie;iiyl)-8//-fJ.-:t-1o}(azino('23-/]quinolin-8-one (Compound 124. Structure 11 of Scheme II. where. R; . R3. R4. R5, = H. R2 = tnfluoromethvl R6 = ;-Pr, R13 = CH2CC1FZ): Compound 124 was prepared according to General Method 4 (EXAMPLE 1) from (3A')-4-ethyl- 3,4-dihydro-S-isopropoxy-3-methyl-10-(trifluoromethyl)-2A7- [1,4Joxazinoj2,3-_/]quinoline (22 mg, 0.02 mmol) in 2 ml, acetic acid and 2 mL concentrated HC1 and heated at 90°C for 4 h to afford 14 mg (72%) of Compound 124, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes:EtOAc, gradient elutiori). 1U NMR (500 MHz, CDC13) 5 12.10 (bs, 1H), 7.25 (d. J= 9.3, 1H), 7.14 (s. 1H), 6.^8 (d, J= 9.3, 1H). 4.58 (dd. J= 10.7, 1.3, IE), 4.10 (m, Iff). 3.94 (dd, J = 10,7,2.4, 1H). 3.78 (m, Iff), 2.96 (bd, J= 9.8, 1.H), 1.81 (m, 1H), 1.00 (d, J= 6.8, 3H), 0.9S id. J=6.S, 3H). EXAMPLE 25 (3^)-4-(2.2-difluoroethvlV2.3.4,7-tetrahvdro-3-isoproT?vl-10-(trifluoromethvlV8Fri! 41oxazmol'2?3.-/]quinglin-8-one (Compound 125. Structure 11 of Scheme II. where R1, R'. R\ R5. = H. R? = trifluoromethyl. R6 = z'-Pr. R13 = CH2CHFZ) Compound 125 was prepared according to General Method 6 (EXAMPLE 3) from (3A!)-3,4-dihy(iro-S-isopropoxy-3-isopropyl-10-(trifluoromethyl)-2H'-[l,4]oxazino[2,3- /Jquinoline (3u rug, 0.1 mmol) and NaBH4 pellets (large excess, >10 equiv) in 5 mL difluoroacetic acid (0.02 M) stirred at rt for 12 h, to afford 28 mg (79%) of (3^)-4-ethyl- 3,4-dihydro-H-isopropoxy-3-isopropyl-10-(trifluoromethyl)-2//-[l,4]oxazino[2,3- /jqumolme. 'H NMR (500 MHz, CDC13) 7.44 (d, J = 9.3, 1H), 7.30 (d, J = 9.3, 1H), 7.21 (s. 1H), 5.98 (m, 1H), 5.49 (m, 1H), 4.55 (dd, J = 10.7, 2.4, 1H), 3.84 (dd, J = 1.0.7, 2.4, 1H), ?.79 (m, 1H), 3.54 (m, 1H), 2.93 (m, 1H), 1.84 (m, 1H), 1.39 (d, J - 6.3, 3H), 1.38 (d, J - 6.3, 3H), : .00 (d, J = 9.8. 3H), 0.99 (d, J = 9.8, 3H). This material (13 mg, 0.03 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 3 mL acetic acid and 3 mL concentrated HC1 heated at 90°C for 4 h to afford 8 mg (70 %) of Compound 125, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes BtOAc, gradient elution). {H NMR (500 MHz, CDC13) 5 11.59 (bs, 1H), 7.15 (d, ./ --• 'H.S. IH'i. ".13 (s, Hi). 6.94 (d, .7-8.8, 1H), 5.96 (m, 1H), 4.55 (dd,.7=10.7, 1.3. 1H), 3.8'7 (dd,,/ - ; 0 7. 2.4, 1H), 3.74 (m, 1H), 3.50 (m, 1H), 2.91 (bd, J= 8.8, 1H), 1.80 (m, 1.H K i .00 (d../ - 11.7, 3HX 0.97 (d, J= 11.7, 3H). EXAMPLE 26 (MH-A!hl:2J.A7-^ fl£!:Lk'j?]inii-l\ne (Cgmpound 126. Structure 11 of Scheme IL where R1, R3, R4. Rs. = H, RJ:: tniluororneihvl. R6 = z-Pr, R13 = CH7CHCH2) A 5us])ension of (37?)-3,4-dihydro-8-isopropoxy-3-isopropyl-10-(trifluoromethylj- 2H-\ 1.4]oxazmo[2,3-/jquinoline (0.010 g, 0.028 mmol) andK2CO3 (0.019 g, 0.140 mmol) in DMT (1.0 mL) was treated with allyl bromide (0.024 mL, 0.280 mmol) and heated at 5°C for i i.i h. The reaction mixture was poured into 25 mL- water and extracted with EtOAc i 2 x 25 mL). The extracts were washed with 25 mL each water and brine, dried over MgSOj, filtered and concentrated to a yellow oil. Column chromatography (5-10% EtOAc in hexane gradient) gave 0.010 g (91%) of (3£)-4-allyl-3,4-dihydro-S-isopropoxy- 3-isopropyl- 1 0 --(trifluoromethyl)-2^-[ l,4]oxazino[2,3-_/]quinoliiie, a yellow oil. This material (0.006 g, 0.015 mmol) was earned on according to General Method 4 (EXAMPLE' 1 ) by treatment with cone. HC1 (1 .0 mL) heated at 70°C for 1 h to afford O.OU4 g (80%) of Compound 126, a yellow solid. Rf 0.6 (9:1 CH2Cl2;MeOH); !H NMR (400 MHz. CDC13) 8 1 1,82 (broad s, 1H), 7.12 (d, 1H, J= S.9), 7.1 1 (s. 1H), 6.93 (d, 1EL J - S.9), 5.92-5.81 (m, 1H), 5.27-5.17 (m, 2H), 4.48 (d, 1H, /= 10.9), 3.99 (dd, ABX, 1H, J = 16.4. 5.8), ), 3.84 (dd, ABX, 1H, J= 16.4, 5.8), 3.77 (dd,A£X, 1H, J = 10.9, 2.8), 2.96- 2.93 (m, 1 H\ i .94-1.84 (m, 1H), 0.98 (d, 3H, .7= 6.7), 0.96 (d, 3H, J= 6.7). EXAMPLE 27 i 2 ^LbL. 3_.4 /2 - retrahydro-3-phenyl-10-(tnfluoromethvl)-8//-ri,41oxazmo[23-/]qiiinolin-Sone (Compound 127. Structure 9 of Scheme II. Avhere R1. R3. R4. R5. = E, R2 = in 1 1 t-IQrc irietb vj . .._B-_!^Ph) i.27 (iriiliioromethyljquinpline (Structare 7 of Scheme II, where R'. R", R4. R;\ = H. R" = D.'li^Jiyi™i^tl/y]-i_R^-±£hl: ^ms compound was prepared according to General Method 1 (tXAMPLF. I ) from 6-bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinoline (500 mg, L43 rnrnoii. (2jI?)-(-)-A'-f-butoxycarbonyl-2-phenylglycino] (542 mg, 2.28 mmol), tnphcnylphosphme (615 mg, 2. 28 mmol), diisopropyl azodicarboxylate (462 mg, 2.28 mnioii and 4-methylmorpholine (570 mg, 5.64 mmol) in 15 mL THF to afford 295 mg (36%i or (27\)-6-bromo-5-[(2'-/-butoxycarbonylammo)-2'-phenylethoxy]-2-isopropoxy-4- (rnfiuoromethyl)qiiinoline, a colorless oil, after column chromatography (1:1 EtC)Ac:hexanes). 1H NMR (400 MHz. CDC13) 5 7.78 (d, 1H, J= 9.0), 7.55 (d, 1H, J = 9.0). 7.39-"7.24 (m, 6H), 5.52 (septet IB, J= 6.2), 5.23 (s, 1H), 4.1 1 (m, 2H), 4.02 (m, 1H). 1.45-i.:;0im, 15H). f ! .4ioXdjiiiK)| 2.3-/1qumolme (Structure 8 of Scheme II. where R1. R3. R4. R'\ =H. R2 ^ tiifliioromethvl. R° = Ph): This compound was prepared according to General Method 2 (E X AMP LE 1 ) from (2'^)-6-bromo-5-[(2'-f-butoxycarbonylammo)-2'-phenyletlioxy]-2- isopropoxy-4-(tnfluoromethyl)quinoline (295 mg, 0.52 mmol) in C^CL (5 mL) and TFA (5 ml ) TO give 243 mg (100%) of (2'^)-6-bromo-5-(2'-amino-2'-phenylethoxy)-2- isopropoxy-4-(trifluoromethyl)quinoline, an amber oil. This matenal (243 mg, 0.52 mmol) was earned on according to General Method 3 (EXAMPLE 1 ), by treatment with Pd2(dba)3 (24 mg, 0.026 mmol), BINAP (32.2 mg, 0.052 mmol) and sodium z--butoxide (70 mg, 0.73 mmol) in 8 mL toluene to afford 123 mg (61%) of (3^)-3,4-dihydro-8- isopropoxy-3-phenyl-10-(tnfiuoromethyl)-2//-[l)4]oxazino[2.3-_/]quinoline. a yellow solid, alter column chromatography (9:1 hexanes:EtOAc). 3H NMR (400 MHz, CDC13) 5 7.63-7.02 (ra. 8H), 5.49 (septet 1H, J= 6.2), 4.62 (dd, 1H,7= 8.3, 3.2), 4.45 (dd. 1H, ,/ = 10.6, 3 . 2 \ 4 . l 2 ( s , 1H), 4.02 (dd, lH,/= 10.6, 8.3) 1.40 (d, 3H,J= 6.2), 1.39 (d, 3H, J = 0.2). (3/?)-^23.4:7-Tetrahvdro-3-phenvl-10-(trifluoromethvl)-8flr-[1.41oxazmor2.3- /IqmnQlin-S-one (Compouiid_127, Structure 9 of Scheme II. where R1. R3. R4. R\ = H, R2 Compound 127 was prepared according to General Method 4 (EXAMPLE 1) from (3A1)-3,4-dih\'dro--8-isopropoxy-3-plienyl-10-(trifluoromethyl)-2//-[l,4]oxazmo[2,3~ /Iqumohne (33.3 mg, 0.086 mmol) in 4 mL AcOH and 4 mL cone. HC1 to afford 15.5 mg (52% ) of the Compound 127, a yellow solid, after column chromatography (1:1 EiOAc:hexaiies). !H NMR (400 MHz, CDC13) 5 11.6 (s, 1H), 7.40 (m, 5H), 7.14 (s, 1H), id, I H . , . ' - = 8.6), 6.95 (d, 1H, ,7= 8.6), 4.58 (m, 1H), 4.44 (m, 1H), 4.03 (m, 2H). EKAJVIPLE 28 O.^i: JLLi J: ;retrahydrQ-3-pheny]-4-(2.2,2-trifluoroethyl)-10-(trifluoromethyl)-8/f- [ 1 .4]oxazmo[ 2^3 -/]quiriolin-8-one (Compound 128. Structure 11 of Scheme II, where R , R'. R"1. R-. = FL R2 = trifluoromethyl, R6 = Ph. R13 = CHgCF^) ( 3A' )- 3 .;4-Dihvdro-8-isopropoxv-3-phenyl-4-(2.2,2~trifluoroethyl)-l 0- (lrLllupToiTiedjyl)-2//-ri,41oxazino[2.3:/]quinoline (Structure 10 of Scheme II. where R!. R R4. Rj. r EL R- = trifluoromethyl, R6 = Ph. R13 = CHgCFQ: This compound was prepared according to General Method 6 (EXAMPLE 3) from (3J?)-3,4-dihydro-8- isopropoxy-3-phenyl-10-(trifluoroiTiethyl)-2^-[l,4]oxaziiio[2,3-7]quinoline (49.5 mg, 0. i 27 mmol ) and NaBH4 (300 mg, 7.9 mmol) in 5 mL TFA, to afford 50.7 mg (85%) of (3/?Vv3,4--dihydro-8-isopropoxy-3-phenyl-4-(2,2.2-tnfluoroethyr)-10-(triiluoromethylj-2Ar- [l.-joxazmo 2,.3-_/]quinolme, a yellow solid, after column chromatography (1:3 ClLCkhexanes), 'H NMR (400 MHz, CDC13) 5 7.55-7.10 (m, 8H), 5.50 (septet, 1H, J = 0.2), 4,77 (dd, IH, 7 = 4.4, 3.4), 4.39 (dd, 1H,J= 11.0, 3.4), 4.29 (dd, 1H, 7= 11.0,4.4), 4,1 0 (m, 1H), 3.66 (m, 1H), 1.40 (d, 6H, /= 6.2); (3/g)-23.4.7-TetraJivdro-3-phenvl-4-r2a.2-trifluoroethvl)-10-(trifluorometlwlV8Ffl. 4]Qxazinor2.3-/1quinolin-S-one. (Compound 128, Structure II of Scheme II. where RSIRi-Rl'jJ: H. R2 = tnfluoromethvl R° = Ph, R13 = QfoCFQ: Compound 128 was prepared according to General Method 4 (EXAMPLE 1) from 1 3/0-3. 4 •dihydro-8-isopropoxy-3-phenyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-2//- [ 1 ,4joxazmo[2.3":/]qumoline (50.7 mg, 0. 1 1 nxmol) in 2 mL AcOH and 2 mL cone. HC1 to afford 32.4 mg (70%) of the Compound 128, a yellow solid, after column chromatography ( 1 : 1 EtO.Ac-.hexane). !H NMR (400 MHz, CDC13) 8 11.0 (s, 1H), 7.40-7.05 (m, 8H), 4.74 uld. IH. J •-•-= 4.0, 3.2), 4.39 (dd, 1H, 7 = 1 1.0, 3.2), 4.29 (dd, IH, 7 = 1 1 .0, 4.6), 4.04 (m, !.H1 3.63 ( n i , I H ) . EXAMPLE 29 l3AM-4"(;vclopixrL3yjmethyj-2.3,4,7-tetTahvdro-3-phenyl-10-(trifluoromethvl)-8/:/- | 1.41oxazinp|.2..3-/lquinolin-8-one (Compound 129. Structure 11 of Scbeme II, where R'. R\ K4. R5. •- 1-1. R- = trill uoromethvl Rb = Ph. R13 = CHrcvclopropvn ("ompdund 129 was prepared according to General Method 5 (EXAMPLE 2) from t 'ornpound 1 2.X ( EXAMPLE 28) (1 1.6 mg, 0.034 mmol), cyclopropanecarbox aldehyde (282 mg, 4.0 mmol), AcOH (104 mg, 1.75 mmol) and NaCNBH3 (150 mg, 2.39 mmol) in 3 ml. MeOH to afford 8.4 mg (63%) of Compound 129, a yellow solid, after column cliromatographv (1:1 EtOAc:hexane). JH NMR (400 MHz, CDC13) 5 11 .2 (s, IH), 7.40- 2 (m. oH), 7. 14 (s. IH), 7.07 (d, IH:. ,7= 9.0), 4.77 (dd, IH, ,/== 6.6, 3.6), 4.33 (dd, IH, ,/ = K).S>. 3.6 i. 4.15 (dd, \B,J= 10.9, 6.6), 3.62 (dd, 1H,J= 15.3, 4.6), 2.65 (dd, IH, 7 = 1 5. 3. 7.9), 0.»4 (in, IH), 0.51 (m, IH), 0.40 (m, IH), 0.13 (m, IH), -0.06 (in, IH). EXAMPLE 30 (3^)-3-Benzv]-2,3.4,7-tetrahvdro-4-(2.2,2-trifluoroethyl)-lQ-(tnfluoromethvl;)-8JHrf. L4]oxazino.f2.3-/lquinolin-8-one (Compound 130. Structure 11 of Scheme II, where R1. R\ PA R'. = H. R2 = trifluoromethvl. R6 = benzyl, R13 = CH^CFi) (2'/?)-6-Bromo-5-[r2'-^-butpxvcarbonylamino)-3'iphenyl-_r-propoxv1-2- isopropoxv-4-(trifluoromethvl)quinoline (Structure 7 of Scheme II. where R1. R3. R4. R5. =jH, R2 = jrifluoromethyl. R6 - benzyl): This compound was prepared according to General Method 1 (EXAMPLE 1) from the bromophenol (525 mg, 1.5 mmol), (£)-(+)-//- /-butoxycarbonyl-2-ammo-3-phenyl-l-propane! (603 mg, 2.4 mmol), tnphenylphosphine (646 mg, 2,4 mmol). diisopropyl azodicarboxylate (514 mg, 2.5 mmol) and Nmethylmorpholine (607 mg, 6.0 mmol) in 15 mL THF to afford 212 mg (24%) of (2'£)-6- bromo-5-[(2'-,'-butoxycarbony]amino)-3'-phenyl-r-propoxy]-2-isopropoxy-4- (tnfluoromethyi)qmnoline, a colorless oil, after column chromatography (1:9 EtOAcrhexane). 'll NMR (400 MHz, CDC13) 5 7.78 (d, 1H, J= 9.0), 7.54 (d, 1H, /= 9.0), 7.32-7.1 S (m, 6H), 5,52 (septet, 1H, ./= 6.2), 4.87 (s, 1H), 4.36 (m, 1H), 4.03 (m, 2H), 3.09 (m, \H\ 1.45-1.20 (m, 15H). (3J? )-3 -Beuzy 1-3,4-dihydro-S-isopropoxy-1 Q-(trifluoromethyl)-2/7- [ 1,4lQxazinoj 2.3-flqumoline (Structure 8 of Scheme II. where R1. R3. R4. R5, = H. R2 = trifluoromethvL R° - benzyl): Tins compound was prepared according to General Method 2 (EXAMPLE 1) from (2'/?)-6-brorno-5-[(2'-i-butoxycarbonylamino)-3'-phenyl-rpropoxy]- 2-is()propoxy-4-(trifluoromethyl)quinoline (212 mg, 0.365 mmol) in CELCL (5 mL) and TFA (5 mL) to give 176 mg (100%) of (2'#)-6-bromo-5-(2'-amrno-3'-phenyl-lTpropoxy)- 2-isopropoxy-4-(trifluoromethyl)quinoline, an amber oil. This material (176 mg, 0.3(i5 mmol) was carried on according to General Method 3 (EXAMPLE 1) by treatment with Pd2(dba)3 (16.7 mg. 0.018 mmol), BINAP (22.7 mg, 0.036 mmol) and sodium t-butoxide (52.6 mg, 0.55 mmol) in 10 mL toluene to afford 26.2 mg (18%) of (J?)- 3-ben2:yl--3,4-diiiyclro-8-isopropoxy-10-(trifluoromethyl)-2Ar-[L4]oxazino[2,3-/lquinoline, a yellow solid, after column chromatography (1:9 EtOAc±exane). 'H NMR (400 MHz, CDC13) 8 7.42--. 15 (m, 7H), 6.96 (d, 1H. J= 9.0), 5.47 (septet, 1H, J= 6.2), 4.35 (dd, 1H, J= 2.8, 10.5). 4.02 (dd, 1H, ./= 10.5, 6.6), 3.82 (s, 1H), 3.75 (m, 1H), 2.91 (dd, 1H, J = 5.6. 13.3). 2.~5 (dd. 1H, J = S.6, 13.3), 1.38 (d, 3H, J=6.2), 1.37 (d, 3H, 7=6.2). (3./?)-3-Benzylr3,4-dihvdro-8-isopropoxy-4-r2.2.2-trifluoroethyn-lQ- (tnlluorQmethyl)-2ff-ri.41oxa2ino[2,3-/]quinoline (Structure 10 of Scheme II. where R1, R:\ R4. R'\ =- H. R:: = trifluoromethvl R6 = benzyl R13 = CEhCFQ: This compound was prepared according to General Method 6 (EXAMPLE 3) from (3^)-3-benzy]-3,4-dihydroiS- isopropoxy-10-(tnfluoromethyl)-2//-[l,4]oxa2ino[2,3-_/]quinoline (25.8 nig, 0.064 minol) and NaBH4 (300 mg, 7.9 ramol) in 3 mL TFA, to afford 29.6 mg (95%) of (3/Z)-3- benzyI-3.4-dihydro-8-isopropoxy-4-(2,2,2-trifluoro ethyl)-! 0-(trifluoromethyl)-2^T- 1 ,4]oxazino[2,3-/]qumolme, a yellow solid, after column chromatography (1:9 EtOAc:hexane). '.H NMR (400 MHz, CDC13) 5 7.51-7.10 (m, SH), 5.51 (septet, 1H, J = 6.2), 4,29 (U 1 H, J= 10.5), 3.91 (m, 2H), 3.70-3.50 (m, 2H), 2.90 (dd, 1H, 7= 6.3, 13.3), 2.80 (dd. IH, J'= 9.2, 13.3), 1.39 (d, 6H, J = 6.2). (3y^-3-Ben2yl-23,4J-tetraliydro::4-(2,2,2-trifluoroethv])-10-(trifluoromethyl)-8Ari l,4|ox:d7,rnoJ2.3-/1qumol.m-8-one (Compound 130. Structure 11 of Scheme II. where R1. R3. R4. R5. -= H. R2 = trifluoromethvl. R6 = benzyl, R13 = CHZCF3): Compound 130 was prepared according to General Method 4 (EXAMPLE 1) from ( :-R }- 3-ben7v I - 3 .4-dibydro-8-isopropoxy-4-(2,2,2-trifluoroethyl)-l 0-(trifluoromethyr)-2/f- 1 1 .4 joxazinoj 2,.v/]qumoline (29.6 mg, 0.061 mmol) in AcOH (3 mL) and cone. HC1 (3 ml.) to afiont 20.2 mg (75%) of the Compound 130, a yellow solid, alter column chromatography ( 1 : 1 EtOAc:hexane). JH NMR (400 MHz, CDC13) 5 1 1.0 (s, IH), 7.37- T.04 (m. SH), 4.29 (d, IH, J= 10.6), 3.93-3.80 (m, 2H), 3.65-3.48 (m, 2H), 2.90 (dd, IH, J = 0.2, 1 3.3), 2.78 (dd, IH, /= 9.2, 13.3). EXAMPLE 31 3.4.7-Tetrahydro-10-(trifluoromethvlV87:/-ri.41oxazino[2.3-/rlquinolin-8-one ( Compound 131. Structure 9 of Scheme II. where R1. R3. R4, R5. R", R7. Rs = H. R2 = (27f)-6-Bromo-5-r(2'-.':-butoxvcarbonyiamino)ethoxv1-2-isopropoxv-4- (iriflu.oromethyl)quinolme (Structure 7 of Scheme II. where R1. R3. R4. R', R6, - H. R2 - Sillyororriethvl]: This compound was prepared according to General Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinolme (533 mg. ] .51 mmol i, vV-butoxycarbonyl ethanolamine (270 mg, 1.67 mmol). tnphenylphosphine ("43S mg, 1.67 mmol) and DLAJ) (0.33 mL, 1.67 mmol) in 15 mL THF to afford 31 7 mg (42%) of 6~bromo-5-[(2W-butoxycarbonylamino)ethoxy]-2-isopropoxy- 4-(tnfluoromethyl)qumoline after purification by flash chromatography (silica gel, 100% hexanes to 1 0% ethyl acetate/hexanes, gradient elution). 'H NMR (CDC13) 5 7.80 (d, J = 9.0, 1H). 7.56 (d, /=-- 9.0, 1H), 7.30 (s, 1H), 5.53 (rn, 1H), 5.19 (br s, 1H), 4.08 (m, 2H), 3.oO (m. 2H), 1 .48 (s, 9H). 1.41 (d, J= 6.1, 6H). 3,4-pihydr_p-8-isQpropoxy-10-(trifluoroniethyl)-2//-ri.4loxazmo[2,3-f|quinolme (Structure 8 of Scheme II. where R'. R3. R4. R5, R6, = H, R2 = tnfluoromethyl): This compound was prepared according to General Method 2 (EXAMPLE 1) from 6-bromo-5- [(2'-r-butoxycarbonylamino)ethoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline (208 mg, 0.42 mmol) in 5 mL of methyl ene chloride and 5 mL of trifluoroacetic acid to afford 78 mg (47%) of 6- bromo-5-(2'-aminoethoxy)-2-isopropoxy-4-(trifluoromethyl)quinoline. This material (78 mg) was carried on according to General Method 3 (EXAMPLE 1) by treatment with sodmm tert-butoxide (26.9 mg, 0.28 mmol), BINAP (5.0 mg, 0.008 mmol)., Pd;(dba):: (3. 7 mg, 0.004 mmol) and toluene (1.3 mL) heated at reflux overnight to afford 52.5 mg (84%) of 3,4-dihydro-S-isopropoxy-l 0-(tnfluorornethyl)-27/-[ 1 ,4]oxazino[2,3- /Jquinolmc, a yellow oil, after flash chromatography (2% ethyl acetate/hexanes to 50% ethyl acetate/hexanes, gradient elution). 1R NMR (400 MHz, CDC13) 6 7.36 (d, ./= 8.8, HI). T . 1 8 ( s , 111), 7.03 (d,J=8.8. 1H), 5.47 (m, 1H), 4.67 (br s, 1H), 4.31 (dd, 7 = 4.5, 4 . 5 . 2Hi. 3..S4 (dd,. 7 = 4.4. 4.3, 2H), 1.38 (d, J= 6.2, 6H). ;i3A7-Tetrahy^-o-10-(tnfluoromethvl)-8/f-ri.41oxazm (Compound 13.1 . Structure 9 of Scheme II. where R1. R3. R4. R5. R6. = H. R: = Compound 131 was prepared according to General Method 4 (EXAMPLE 1) from 314-dihydro-lS-isopropoxy-10-(trifluoromethyl)-2^r-[l,4]oxazino[2,3:/]quinoline (10 mg, 0.032 mmol) in 0.64 mL glacial acetic acid and 0.32 mL cone. HC1 heated at 70°C for 90 minutes to afford 5 mg of Compound 131 after flash chromatography (4:1 hexanes: EtO Ac). 1H NMR (400 MHz, acetone-d6) 5 10.85 (br s, 1H), 7.01 (d, J= 8.62, I h f ) , 6.91 (d, ,7- 8.64, 1H), 6.86 (s, 1H), 4.26 (m, 2H), 3.46 (m, 2H). EXAMPLE 32 2.3.4.7-Tetralrvdro-4-(2.2.2-trifluoroethyn-10-CtriiluoromethylVS//-[1.41oxazinor2.3- /lquinoh'n-S-one (Compound 132. Structure 11 of Scheme II, where R1. R3, R4. R5, Rb. = H. R' = trifluoromethyl. R13 = CH2CF3) Compound 132 was prepared according to General Method 3 (EXAMPLE 1) from 3.4-dihydro-S-isopropoxy-10-(trifluoromethyl)-2fl"-[l,4]oxazino[2,3-/lqumoline (20.0 mg, 0.064 mrnol > and sodium borohydride (excess of 20 mg) in 3 mL trifmoroacetic acid to afford 25 mg (ca. 100%) of 3,4-dihydro-8-isopropoxy-4-(2,2,2-trifluoroethyl)-10- (tniluoromeihyl)-2//-[L4]oxazmo[2,3-/jquinoline, a red oil. No further purification was performed and the material was directly transformed according to General Method 4 (EXAMPLE 1) from 3,4-dihydro-8-isopropoxy-4-(2,2,2-trifluoroethyl)-10- (tnfluoromethyl )-2f/-[l,4]oxazino[2,3-/]qumoline (25 mg) in 0.32 mL cone. HC1 and 0.64 mL glacial acetic acid heated at 7()°C for 90 minutes to afford 11 mg (49°'-) of Compound 132 after purification by flash chromatography (9:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). lli NMR (400 MHz, acetone-d6) ft 11.05 (br s, 1H). 7.3 1 (d, /= o.o, 1H), 7.04 (d, J= 8.8, 1H), 6.92 (s, 1H), 4.32 (t, J= 4.3, 2H), 4.14 (q,J = 9.5.2H). 3.0! (t. ,7=4.4, 2H). EXAMPLE 33 ( "AgJO.a^VL7_a,S,9,10,] Qa-Hexahydro-7-methyl-1 -(trifluoromethylV4/7- cvclopentaj5.t5i| 1.41oxazino|'2,3:/lqmnolin-3-one (Compound 133. Structure 11 of Scheme.11,..where R!. R4. R5. = H. R2 = tnfluoromethyl. R3. R6 = -CH2CHZCHZ-. R13 = CHJ L21/il-j>Bromo-5 -[ O'-f-butoxycarbonylamino V1 '-cvclopentoxv'l -2-isopropoxy-4- (trifluQjomethyriqumolme (Structure 7 of Scheme II, where R1. R4. R?. = H. R2 = IliflliQroill^.yLRiLR^j^HgCH^CHg^): The compound was prepared according to Cienerai Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4- (tTitluorometliyl)quinolme (0.50 g, 1.43 mmol). (i^,2^)-2-7V-t-butoxycarbonylamino-lcyclopentanol (460 mg, 2.28 mmol), tnphenylphosphine (600 mg, 2.2S mmol) and diisopropyl azodicarboxylate (0.45 ml, 2.28 mmol) in 0.6 mL Tv'-methylmorpholine in 14 mL dry THF to afford 190 mg (25%) of (2'J?)-6-bromo-5-[(2'-r-butoxycai-bonylamino)-l'- cyciopentoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline after flash chromatography (100% hexanes to 6:1 hexanes/EtOAc, gradient elution). !H NMR (500 MHz, CDC13) 5 7.78 (d;7 = 8.8, 1H), 7.49 (d,7 = 8.8, 1H), 7.24 (s, 1H), 5.52 (m, 1H), 5.28 (d, 7 = 9.3, 1H), 4.96 (m, 1H), 4.1 1 (m, 1H), 2.04 (m, 2H), 1.82 (m, 2H), 1.59 (m, 2H), 1.45 (s, 9H), 1.42(d,,/= 7.8, 3H), 1.41 (d,7=7.8,3H). ( 2' R ) -6-.Bromo-5-(2'-amino-r-cyclopentoxy)-2-isopropoxv-4- ( tnfluoromeihvl )quinoline : This compound was prepared according to General Method 2 (EXAMPLE 1 ) from (2'^)-6-bromo-5-[(2'-/-butoxycarbonylaniino)-l'-cyclopentoxy]-2- isopropoxy-4-(trifluoromethyl)quinoline (190 mg, 0.35 mmol) in 3 mL CBbCb and 3 mL TFA to afford 133 mg (86 %) of (2'/?)-6-bromo-5-(2'-amino-r-cyclopentoxy)-2- isopropoxy-4-(trifluoromethyl)quinoline. hexahydrocyclopenta[5,6iri,41pxazino[2,3-/1quinoline (Structure 8 of Scheme II. where R1. R4. R5. - H. R3 = tnfluoromethvl R:\ R6 = -CHhCHgCHg-j: This compound was prepared according to General Method 3 (EXAMPLE 1) from (27?)-6-bromo-5-(2'-arnino- 1 '-cyclopenti)xy')-2-isopropoxy-4-(trifluoromethyl)quinoline (133 mg, 0.37 mmol), (±)- 2.2'-bis(diphenylphosphino)-l,r-binaphthyl (7.6 mg, 4 mol%), Pd2(dba)? (5.6 mg, 2 rnol"o). sodium r-butoxide (41 mg, 1.19 mmol) to afford 73 mg (68%) of (7a#,10a6>- 7,7a.8,9. 1 0. J ()a-hexahydro-3-isopropoxy-l-(trifluoromethyl)- c vciopemai :.-,6j[ i .4]oxazino[2,3-/jquinoline after purification by flash chromatography ( 1 00% hexanes to 4:1 hexanes:EtOAc, gradient elution). 1R NMR (500 MHz, CDC13) 5 7.38 (d. 7- S.8. 1H), 7.18 (s, 1H), 7.04 (d,7= S.8, 1H),- 5.47 (m, 1H), 4.13 (m, 1H), 4.06 is, ! H)., 3.78 (m, 1H)/2.06 (m, 2H), 1.96 (m, 2H), 1.65 (m, 2H), 1.38 (d, 7= 5.9, 3H), 1.37 (d. .7=6.4, 3H") (:;a/^10a.SV7.7a.8.9J0.1Qa_-Hexahvdro-7-methYl-l-(tnfluoromethyl)-4^- cvcl_openta|.5.6ir.l.,41oxazinQ[23-/].quinolin-3-one (Conipound 133. Structure 11 of Scheme II, where R!. R4. R5., = H. R2 = tnfluoromethvl. R3, R6 = -CH2CH2CH2-. Ellii-CH;}: Compound 133 was prepared according to General Method 5 (EXAMPLE 2) from i.7aJOa5)-"",7a,S,9,10.10a-hexahydro-3-isopropoxy-l-(trifluoromethyl)- cyciopenta[5,6][L4]oxazino[2,3-/]quinoline (5 mg, 0.014 mmol), 37% aqueous tomialdehycie solution (0.01 mL, 0.14 mmol) and NaBH3CN (9 mg, 0.14 mmol) in 1 mL acetic acid to afford 5 mg of (7a#,10aS)-7.7a,8,9,10,10a-hexahydro-3-isopropoxy-7- methyl-] -(tnfluoromethyl)-cyclopenta[5,6][l,4]oxazino[2,3-/]quinoline. This material (5 mg, 0.01 mmol) earned on according to General Method 4'(EXAMPLE 1) by treatment with 4 mL o t ' l : 1 acetic acidrconcentrated HC1 (3 mM) heated at 90°C for 4 h to afford 3:9 mg (90%) oi"Compound 133, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). !H NMR (500 MHz, CDC13) 8 10.58 ibs. 111), 7. 1 0 ( s , 1H), 7.00 (d,. 7=8.8, 1H), 6.87 (d, J= 8.S, 1H), 4.15 (m, 1H), 3.53 (m, 1H), 2.9.S (s, 3H), 2.02 (m, 4H), 1.64 (m, 2H), 0.88 (t, J= 6.8, 3H). EXAMPLE 34 (7a^.l()a6')-^-Ethyl-7.7a.8,9JQjOa-hexahvdro-l-(trifluoTOmethvl)-4//- cvclopentaJ5,61| l341oxazino[2,3-/]qumolin-3-one (Compound 134, Structure 11 of Scheme II, where R1, R4. Rj.. = H, R2 = tnfluoromethvl. R3. R6 = -CHbCHgCH?-. R13 = CH3.CH2J Compound 134 was prepared according to General Method 5 (EXAMPLE 2) from (7 a, 1 Oai'V 7,7a,8,9,10,1 Oa-hexahydro-3-isopropoxy-1 -(trifluoromethyl)- cvclopenta 6.6 j[ 1,4]oxazino[2,3:/]quinoline (5 mg, 0.014 mmol) and NaBH4 pellets (->! 0 equiv) m > mL acetic acid to afford 5 mg of (7aJ?,10a1S')-7-ethyl-7,7a,8,9,10,10ahe. xaliydro-3-jsopropoxy-l-(trifluoromethyl)-cyclopenta[5.6][],4]oxazino[2,3-/]quinoline. This material (5 mg, O.Oi mmol) was earned on according to General Method 4 (EX.AJVtP.LE 1) by treatment with 4 mL of 1:1 acetic acid:conceatrated HC1 (3 mM) and heated at 90°C for 4 h to afford 4 mg (89%) of Compound 134, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). 1H NMR (500 MHz, CDC13) 5 11.01 (bs, 1H), 7.10 (s, 1H), 7.01 (d, J= 8.8, 1H), 6.90 (d, / = S.S, 1H). 4.00 (m, 1H), 3.59 (ddd, J= 10.0, 7.1, 3.4 1H), 3.44 (m, 2H), 2.03 (m, 4H), 1.61 (m. 2H), L20(t,y=7.1,3H). EXAMPLE 35 7.7a!8,9JOaOa-Hexahvdro-7-(2.2.2-trifluoroethvni-(trifIuoromethvn-4Arcyclopenta[ 5.?61[1.41oxazino[2.3-/1quinolin-3-one (Compound 135. Structure 11 of Scheme O. where R1, R4. R5. = H. R2 = trifluoromethvl. R3. R6 = -CH?CHzCHr. R13 = Comj>ound 135 was prepared according to General Method 6 (EXAMPLE 3) from (IsJLl Oai"V 7:7a,8,9, 1 0,1 Oa-hexahydro-3-isopropoxy-l -(trifluoromethyl)- cydopenta[5.6][l,4]oxazmo[2,3-/]quinoline (20 mg, 0.057 mmol) and NaBH4 pellets (excess) in 7 mL TFA to afford 20 mg of (7a/?,10a5)-7,7a,8,9,10,10a-hexaliydro-3- isopropoxy-]-(trifluoromethyl)-7-(2,2,2-trifluoroethyl)-cyclopenta[5,6][l,4]oxazino[2,3- /[qumoline. This material (20 mg, 0.046 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with 6 mL of 1:1 acetic acid: concentrated HC1 (0.01M) heated at 90°C for 4 h to afford 15 mg (83%) of Compound 135, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). 'll NMR (500 MHz, CDC13) 5 12.10 (bs, 1H), 7.15 (s, 1H)3 7.10 (d, J= 8.8, IH'K 7 . D I id. J - 8.8, 1'H), 4.14 (m , 1H), 3.94 (m, 2H), 3.72 (ddd, J= 10.5, 7.6, 3.4, 1H), 2. 1 8 (m, 2H'K 2.01 (m, 2H), 1 .68 (m. 2H). EXAMPLE 36 (:r)-(2'5',3l^.)-2.3.4.7.-Tetrahvdro-2.3-dimethvl-4-(2.2,2-tnfluoroethyl)-10- (trifluoromethyl)-Sff-ri.41oxazino[2.3-:/]quinolin-8-one (Compound 136, Structure 11 of Scheme II. whereR1. R4. R5. = H. R2 = trifluoromethvl R3. R6 = Me. R13 = CHZCK) (±)-(2'6'._3'Jl?,)-6-Bromp-5-r(3'-t-butoxvcarbonvlamino)-2'-butoxv1-2-isopropoxv-4- (tnfluQrometiivljqiiinoliiie, (Structure 7 of Scheme II, where R1. R4, R5. R7. R8 = H. R2 = d.'Rr.^^Me). The compound was prepared according to General Method 1 (EXAMPLE 1) from 6-brorno-5-hydroxy-2-isopropoxy-4-(tnfluoromethyl)quinoline (0.30 g, 0.8 nimol), (±)-(2^,3^J-3-7V-t-butoxycarbonyl-2-butanol (405 mg, 2.14 mmol), tnphenylphosphine (562 mg, 2.14 mmol) and diisopropyl azodicarboxylate (0.42 ml, 2. 14 mmol) in 0.24 mL ./V-methylmorpholme in 15 mL dry THF to afford 124 mg (28%) of (i)-(2'5.3y\),)-6-bromo-5-[(3'-/-butoxycarbonylamino)-2'-butoxy]-2-isopropoxy-4- (tnfiuoromerhyl)qumoline after flash chromatography (100% hexanes to 6:1 hexanes/EtOAc, gradient elution). !H NMR (500 MHz, CDC13) 5 7.75 (d, J= 8.8, IH), 7.49 (d, J= 8.8, IH), 7.25 (s, IH), 5.52 (m, IH), 4.93 (m, IH), 4.84 (m, IH), 3.97 (m, IH), 1.45 (s, 9H). 1.43 (d, J= 5.9, 3H), 1.40 (d, J= 6.4, 3H), 1.21 (d, J= 5.4, 3H), O.S7 (d, J = 6.4, 3H). (XH 2 '±>3'R, )-6-Bromo-5-(3'-amino-2'-butoxy)-2-isopropoxy-4- (tnfluoromethvl)quinoline. This compound was prepared according to General Method 2 (EXAMPLE 1) from (±)-(2'6',317?,)-6-bromo-5-[(3l-?-butoxycarbonylamino)-2l-butoxy]-2- isopropoxy-4-(trifluoromethyl)quinoline (124 mg, 0.24 mmol) in 4 mL CHjCk and 4 mL TFA to afford 82 mg (82%) of (±)-(2'5,3'^,)-6-bromo-5-(3'-amino-2'-butoxy)-2- isopropoxv-4-(t.rifluoromethyl)quinoline. (±)-(J^3/?)-3,4rX>ihydro-8-isopropoxv-23-dimethvl-10-(trifliioromethyl)-2/f- 11.4]oxazmo| 2.3-/1quinoline rStructure 8 of Scheme II, where R1, R4, R5. = H. R2 = tntlagromethyl, R3, R6 = Me): This compound was prepared according to General Method 3 (EXAMPI E 1) from (i)-(2'1Sr,3I^,)-6-bromo-5-(3'-amino-2'-butoxy)-2-isopropoxy-4- (tntluororneihyj)quinoline (82 mg, 0.19 mmol), (±)-2,2'-bis(diphenylphosphino)-l.rbmaphthyl (:•> mg, 4 mol%), Pd2(dba):, (3.5 mg, 2 mol%), sodium r-butoxide (26 mg, 0.27 mmol) 10 afford 31 mg (47%) of (±)- (21S',3^)-3,4-diliydro-8-isopropoxy-2,3- dimethyl-l ()-(tnfluorornethyl)-2//-[l,4]oxazino[2,3-_/]quinoline, after purification by flash chromatography (100% hexanes to 4:1 hexanes:EtOAc, gradient elution). 'H NMR (500 MHz, CDC1:.) o 7.35 (d, J= 8.S, IH), 7,18 (s, IH), 7.02 (d, J= 8.8, IH), 5.47 (m, IH), 4.36 (m, IH). 3.79 (bs, IH), 3.57 (m, IH), 1.38 (d, J= 6.3, 3H), 1.37 (d, .7= 6.3, 3H), 1.30 (d, J= 0.8. 3H), 1:19 (d, J= 6.3, 3H). (±V(,'1S1.37?)-3,4-Dihvdro-8-isopropoxv-2.3-dimethyl-4-(2.2.2-tnfluoroethvl)-10- (infliiQipmethylV2ff-[1.41oxazino[2,3-/1quinoline (Stmcture 10 of Scheme II. where R1. R4. RJ. = H, R.: ^ trifluoromethyl R3. R6 = Me. R13 = CHZCFO: This compound was prepared according to General Method 6 (EXAMPLE 3) from (±)-(2,S',3^)-3,4-dihydro-8- isopropoxy-2,3-dimethy]-10-(trifluoromethyl)-2H-[l,4]oxazino[2,3-/lquinoline (17 mg, 0.05 mmol) and NaBEL pellets (>10 equiv) in 4 mL tnfluoroacetic acid (0.01 M) to afford 12 nig (ca. 60%) of (r:)-(21S',3^)-3,4-dihydro-8-isopropoxy-2,3-dimethyl-10- (tniluoromethyi)-2/:/-[l,4]oxazrno[2,3-/]qurnoline. which was carried on without purification. (±)-('26'.3/g)-2,3,4.7-Tetrahvdio-2.3-dimethvl-4-(2.2.2-trifluoroethvl)-lQ- (1rifluQrometJiYl)-8ff-[l;4]Qxazinor2,3-/1quinolin-8'-one (Compound 136, Structure 11 of Scheme II._where R1. R4. R5. = H. R2 = trifluoromethyl, R3. R6 = Me, R13 = CH2CF3): Compound 136 was prepared by General Method 4 (EXAMPLE 1) from (±)- (2S3R)- 3 ,4-dih ydro-8-isopropoxy-2,3 -dimethyl- 1 0-(tnfluoromethyl)-2//- [1.4]oxazmo[2, vy]quinoline (12 mg, 0.03 mmol) in 4 mL of a 1 :1 acetic acid: concentrated HC1 (0.0 1 M) heated at 90°C for 4 h to afford 8 mg (75 %) of Compound 136, a yellow solid, after column chl'omatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). 'll NMR. (500 MHz, CDC13) 5 1 1.96 (bs, 1H), 7.14 (s, 1H), 7.08 (d, J= 9.3, 1H), 6.97 (d,../= 9.3. 1H), 4.20 (m, 1H), 3.77 (m, 2H), 3.34 (m, 1H), 1.41 (d,J= 6.3, 3H), 1.09 (d. ,7 = 6.8, 311). EXAMPLE 37 (6aff)-6jiJJJ.J-Telrahyfc^ (.jianolm-2:one ('Compound 137, .Structure 17 of Scheme III, where R1. R3, R4. R5. R7, Rl±ikE.lr:. trifluoromethvl. R6. R13 = -CH7CH7.CHZ-) ll'LkJJ .-lr-.iJjluorQ.-4rnitrophenyl)-2-pvrrolidinyl1-rnethanol (Stmcture 14 of Scheme III where R: . R4. R:\ R7. R" = H. R6. Rn = -CH2CH7CH7-): A suspension of 3,4- diiluoromtroiienzene (1.57 g, 9.8 mmol), (J?)-2-pyn-olidinemethanol (1.0 g, 9.S mmol) and K;.CC>3 ( 1 .36 g, l-',8 mmol) in 30 mL DMF was heated at 75°C for 20 h, whereupon the mixture was partitioned between water (100 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (1 00 mL) and the combined organic layers washed with brine, dried over Na2S04, filtered and concentrated. Flash chromatography (19:1 CH2Cl2:MeOH) afforded 2.27 g (96%) of (JR)-[l-(2-fluoro-4-nitrophenyl)-2-pyirolidinyl]- methanol, an orange solid. Rf 0.1 7 (7:3 hexanes: EtOAc); ]H NMR (400 MHz, CDC13) 5 7.94 ('dd. Hi. J --•- 9.1, 2.6), 7.S9 (dd, 1H, J= 14.4, 2.6), 6.68 (t, 1H, J= 9.0), 4.25-4.32 (m, 1H), 3.60-3.75 (m, 3H), 3.40-3.50 (m, 1H), 1.95-2.15 (m, 4H), 1.43 (t, IE,J= 5.8). r2 J -c\ \ 1 ,41benzoxazine (Structure 1 SofSche me, IIL where R3. R4. R.5. R7. R8 = H. R6. R13 = -CHSCHZCH:-): A suspension of (Ar)-i !-(2-lluoro-4-nitrophenyl)-2-p\Trohdinyl]-methanol (2.27 g, 9.4 mmol) andNaH (oO% mineral oil suspension, 0.737 g, 18.9 mmol) in 35 mL THF was heated at reflux for 1 h. The reaction was quenched with phosphate buffer and the aqueous layer was extracted with EtOAc. The solution was filtered through Celite and the organic layer was washed with brine, dried over MgS04, filtered and concentrated. Flash chromatography (3:2 EtOAc:hexanes) afforded 476 mg (22%) of (3a#)-2,3,3a,4-tetrahydro-7-nitro-l#- pyrrolo|"2.1-c][ 1. ,4]benzoxazine, an orange solid. Rf0.55 (3:2 hexanes:EtOAc); JH NMR (400 MHz, CDC13) 5 7.87 (dd, 1H, J = 9.2, 2.4)., 7.74 (d, 1H, J = 2.4), 6.44 (d, 1H, J = 8.8). 4.5ft (dd, 1 H../ = 10.3, 3.4), 3.65-3.72 (m, 1H), 3.60 (broad t, 1H, ,7 = S.6), 3.44 (t, IH,J = 10.0), 3.36 (td, 1H,J= 9.8,7.3), 2.15-2.25 (m, 2H), 2.05-2.15 (m, 1H), 1.45-1.55 (m, 1H). (3a/?)-'7--Ammo-2.3.3a.4-t.etrahvdro-lf/-pvrrolo|'2,l-c1[l,4]benzoxazine (Structure 16 of Scheme III, where R3. R4. R5, R7. Rs = H. R6, R13 = -CH^CHgCH?-): A suspension of (3a/ nimol) and 10% Pd-C (28 mg) in 15 mL EtOAc and 15 mL EtOH was stirred under a hydrogen atmosphere overnight. The mixture was filtered through Celite and concentrated to afford 0.39 g (98%) of (3a#)-7-ammo-2,3,3a,4-terrahydro-lF-pyrrolo[2Jd[ T.4]benzoxazme. Rf 0.55 (3:2 hexanes:EtOAc); 'H NMR (400 MHz, CDC13) 5 6.50 (d, I H , , / - = 8.31 6. .1 (d, 1H, .7=2.4), 6.29 (dd, 1H, J= 8.3, 2.4), 4.31 (dd, 1H, .7=8.3, 1.5), 3.37-3.50(0), 3H), 3.31 (broad s, 2H), 3.13 (broad q, 1H, J-8.3), 2.07-2.15 (m, 1H), 1.90-2.05 (m, 2H), 1.40-1.50 (m, 1H). (()a^.)-oa.7.8.!:>-Tetrahvdro-4-('triiluoromethvl)-l/f. 6#-pvrrolo|T.2':4.5in ,41- oxazino-[2,3-/lquinolin-2-one (Compound 137. Stmcture 17 of Scheme III, where R1. RJ, R'\ R5. R7. R8 -•- H, R2 = tnfluoromethvl, R6. R13 = -CH2CHZCHZ-): A solution of (3a^)- 7-amin(>2,3.3a,4-letrahydro-17i'-pyrrolo[2,l-c][l,4]benzoxazine (0.390 g, 2.05 mmol) and ethyl 4.4,4-trifluoroacetoacetate (0.378 g, 2.05 mmol) in 14 mL benzene was heated at reflux for 16 h. whereupon the solvent was removed in vacua. The resultant solid was treated with 7 rnL concentrated sulfuric acid and heated to 100°C for several hours. The solution was poured into ice and neutralized with 6NNaOH and extracted with EtOAc (3 x 40 ml.). The combined organic layers were washed with brine, dried over MgSO*}, filtered and concentrated. Flash chromatography (92:8 CH2Cl2:MeOH) afforded 120 mg of an impure yellow solid. Further purification was performed by reverse phase HPLC (ODS, 5 micron, 10 x 250 mm, 3 mL/min) to afford 5 mg (ca. 1%) of Compound 137. 1R NMR (500 MHz, acetone-dg) 5 10.8 (v. broad s, 1H), 7.07 (d,AB, 1H, J= 8.6), 7.04 (d, 80 AB, 1H,./ = S 6), 0.88 (s, 1H), 4.59 (dd, 1H, J = 10.0, 3.8), 3.38-3.45 (m, 2H), 3.34 (t, 1H, .- 10.0), 3.10-3.22 (m, 1H), 2.12-2.22 (m, 2H), 2.00-2.10 (m, 2H), 1.50-1.60 (m, 2H)! EXAMPLE 38 2,J,4,"-Teti^ihv(irQ-2.2,4-tnmethvl-10-(tnfluorornethvn-8-Hr-|'1.41oxazmQ[2.3-riquinolin-8- one (Compound 138. Structure 17 of Scheme III, where R1, R5, R6. R7, R8 = H. R2 = tnlluoromethyl, RJ RJ R13 = Me) To a solution of 7-amino-3,4-dihydro-2,2,4-trimethyl-2Jf/-l,4-benzoxazine (0.16 g, O.S3 rnniol) in 6 ml. toluene was added ethyl 4,4,4-trifluoroacetoacetate (0.18 mL, 1.25 minol), then the mixture was heated at reflux for 3 h. The solvent was removed under reduced pressure to an oil. This oil was dissolved in 4 mL cone. JLSCU and heated at reflux for 2 h and neutralized by pouring into cold NaOH solution. Flash chromatography afforded Coir! pound 138, a by-product of the reaction. 1H NMR (400 MHz, CDC13) 6 10.SI (hs. 1 H > , 7.12 (s, 1H), 7.06 (d, J= 7.5, 1H). 7.01 (d, .1=1.5, 1H), 3.02 (s, 2H), 2.98 (s, 3HI and ! io is, 6H). EXAMPLE 39 iMiiX d;h 1 oi\ .-3-ethyl-3.4-dihydi-o-4-(2.2.2-trifluoroethvl)-10-(trifliiQromethvlV2/f- U_;4joxazu)x>[2_.L3-/kminoline (Compound 139. Structure 19 of Scheme IV. where R1. RJ. S.LELiilE:. = H. R: = tnfluoromethvl R6 = Et, R!3 = CH2CFQ A solution of Compound 110 (EXAMPLE 10) (48 ing, 0.13 mrnol) in 1.3 mL phosphorus oxychlonde was heated at 80°C for 4 h. The mixture was poured into cold water (20 mL) and saturated NaHCC>3 (10 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with bnne (20 mL), dried over MgSCu, filtered and concentrated. Flash chrornatography (hexanes:EtOAc 4:1) afforded 28 mg (56%) of Compound 1 39, a yellow oil. 'H NMR (400 MHz, CDC13) 5 7.68 (d, J= 9.2. 1H), 7.67 (s, 1H), 7.42 (d, ,7- 9.2, 1H), 4.45 (d,J= 10.8, 1H), 4.00-4.15 (m, 1H), 3.99 (dd, J= 10.8, 2.2, iH). 3.7"-3.90 (m, 1H), 3.35-3.45 (m, 1H), 1.45-1.65 (m, 2H), 1.01 (t,/= 7.4, 3H). EXAMPLE 40 (3^)-3-Ethvl-3.4-dihvdro-8-methoxv-4-(2^2,2-trifluoroethvD-10-(tnfluoromethvl)-2Jy- LL4]oxa2mo[2.3-/1quinoline (Compound 140. Structure 20 of Scheme IV. where R1, RJ. R4. R5. R7. R8 --='H. R2 =: trifluoromethvL R6 = Et R13 = CHZCF3, R1S = OMe) A solution of Compound 139 (EXAMPLE 139) (10 mg, 0.025 mmol) and NaOMe (16 mg, 0.30 mmol) in 2 mL MeOH was heated at reflux for 18 h. The mixture was partitioned between saturated NH^Cl (10 mL) and EtOAc (20 mL). The organic layer was washed with brine (10 mL), dried over MgS04, filtered and concentrated. Flash chromatography (hexanes:EtOAc 4:1) afforded 6 mg (60%) of Compound 140, an offwhite solid, 'H NMR (400 MHz, CDC13) 5 7.49 (d, J= 9.1, 1H), 7.29 (d, J= 9.1, 1H), 7.26 (s, 1H), 4.49 (dd,7= 10.7, 1.5, 1H), 4.04 (s, 3H), 3.97 (dd, J= 10.7, 2.4, 1H), 3.85- 3.95 (m, 1H), 3.75-3.85 (m, 1H), 3.22-3.32 (m, 1H), 1.55-1.65 (m, 2H), 0.99 (t, 7=7.4, 3 Hi. EXAMPLE 41 (l)::3-Ethvi--2J;4J-tetrahydro-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8-//- [ [ .41oxa2ino|'2.3-/1qumoline_-S-orie (Compound 110. Structure 29 of Scheme V. where R1. R3. R4. R3, R; . R.s = H. R2 = trifluoromethvL Rb = Et. R13 = CH;CF.) |2A')-! r)-.2-(2-:Fluoro-4-nitrophenyl)arnino-l-butanol (Structure 21 of Scheme V. where R?. R4. R:\ R7. Rs = H, R6 = Et): A mixture of 118 g (0.74 mole) of 3,4- di fliioromtrobenzene and 85 g (0.95 mole) of 7 -(+)-2-amino-l-butanol was dissolved in 400 mL of absolute ethanol. To this solution was then added 62.2 g (0.74 mole) of sodium bicarbonate. The suspension was stirred and heated at reflux temperature for 12 h when TL.C indicated complete conversion of the 3,4-difluoronitrobenzene. After cooling to room temperature, the reaction mixture was filtered with the aid of additional ethanol and the ethanol was then evaporated. The crude product thus obtained was distilled under reduced pressure (110-112°C, 2 mm Hg) to afford (2fl)-(+)-2-(2-fhioro-4- nin-ophenyl);imino-l-butanol as a red solid. Yield, 162g (96%). [a] D=-f95.4 (CHC13, c 22.7'): 'H NMR (CDC13) 5 7.88 (1H, dd, J = 2.4, 8.9), 7.76 (1H dd J = 2.4, 11.7), 6.66 (1H. dd, J = 8.7), 4.88 (1H, m), 3.76 (1H dd, J = 4.2, 11.2), 3.68 (1H, dd J = 4.2, 11.2), 3.52 (1H. in). 2.63 (1H, bs), 1.70 (1H, m), 1.59 (1H, m), 0.97 (3H, t, J = 7.5). 13C NMR: ppm 150.1, 147.7. 142.8, 142.7, 136.1, 122.3, 110.9, 110.7, 109.5, 63.6, 55.8, 24.4, 10.4. ('2iS1,4/?)-(-)-3-(2-Fluoro-4-nitropheDvl)-4-ethvl-2-(trifluorometfavl)-l,3-oxazolidine (Structure 22 of Scheme V, where R3, R4, R5. R7, Rs = H. R6 = Et. RA = tnfluoromethyl) and (2/)-(T)-3-r2-Fltioro-4-nitrophenyl)-4-ethvl-2-(trifluoromethvl)-L3-oxazolidine (Structure 22 of Scheme V, where R3. R4. R5. R7. R8 = H. R6 = Et. RA = tnfluoromethvl): A 2-L three-necked RJB flask equipped with a Dean-Stark condenser was charged sequentially with 172 g (0.75 mole) of (2^?)-(+)-2-(2-fluoro-4-nitrophenyl)amino-lbutanol, '750 ml, of toluene, 543 g (3.77 mole) of trifluoroacetaldehyde ethyl hemiacetal and 34.4 g o i ' p ••toluenesulfonic acid. The reaction mixture was refluxed with azeotropic removal of water for 10-12 h. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with aqueous sodium bicarbonate, brine and dried over anhydrous MgSCU. After filtration, Ihe solvents were removed under reduced pressure to afford a mixture of the desired oxazoLidines (2S,4J?)-(-)-3-(2-fluoro-4-nitrophenyl)-4-ethyl-2-(trifluoromethyl)- 1.3-oxazolidmc (m'-isomer) and (27?,4J?)-(+)-3-(2-fluoro-4-nitrophenyl)-4-ethyl-2- (tniluonnneuiyl )-l ,3-oxazolidme (trans-isomer) as a low melting solid. The product was found to be j mixture of two diastereoisomers (cis/trans, 4:3). Total yield 230 g (100%). (2o,4ftH -1-..-(2-fluoro-4-nitrophenyT)-4-ethyl-2-(trifluoromethvl)-1,3-oxazolidine (cisisomen: 'H NMR (CDC13) 8 8.01 (1H, dd J = 2.5, 8.9), 7.95 (1H, dd .1 = 2.5, 13.1), 6.95 (1H. t. J -• 8.7), 5.82 (I.H. q, J - 4.6), 4.42 (1H, bt, J = 7.46), 4.27 (1H, m),. 4.08 (1H, d, J = 8.5'), 1.03 i 1 H, m), 1.49 (1H, m), 0.87 (3H, t, J = 7.4). 13C-NMR: ppm 153.2, 150.7, 140.9, 13o.S, 128.0. 125.1, 122.2, 121.2, 119.3, 118.5, 113.5, 113.2, 85.4, 71.4, 59.2, 26.1, 9.3. (~/ii:2-f2-Fluoro-4-mtro(2.2,2-tnfluoroethvnanilmo]-l-butanol (Structure 23 of Scheme V. where R3. R4. R5. R7, Rs = H, R6 = Et. R13 = CHZCF3): A 2-L three-necked RB flask equipped with an addition funnel and mechanical stirrer was charged sequentially with 230 g (0.75 mole) of the mixture of (-)-(2S,4R)- and (+)-(2^,4^)-3-(2-fluoro-4- introphen\T)-4-ethyl-2-(trifluorornethyl)-l53-oxazolidine, 1.0 Liter of dry chloroform and 290 g (2.5 mole) of triethylsilane. The solution stirred under an atmosphere of nitrogen and cooled to '78°C. 161 g (0.85 mole) of TiCLt was added in drops through the addition funnel. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for another 24 h. The reaction mixture was quenched with ice and then neutralized with aq. Na2CC>3. The organic layers were washed with water, brine and dried over MgSO4. After filtration, the solvents were evaporated under reduced pressure and the residue was punfied by silica gel column chromatography (ethyl acetate: hexanes 1: 9i to afford (2^?)-2-[2-fluoro-4-mtro(2,2,2-trifIuoroethyl)anilino]-l-butaiioI as a glassy solid, yield 190 g (82%). 'H NMR (500 MHz, CDC13) 5 7.98 (dd, J = 8.8, 2.4, IHl 7.94 (dd. J - 13.2, 2.9, 1H), 7.37 (dd, I = 8.8, 8.8, 1H), 4.12 (m, 1H), 3.87 (m, 1H), 3.77 (m, 1H), 3.70 (m, 1H), 3.57 (m, 1H)S 1.78 (dd, J = 6.8, 4.4, 1H), 1.58 (dq, J = 7.8, 2.9, 2H), 0.95 (I, J - 7.3, 1H). (4-)-(3^)-3-Ethvl-3.4-dihvdro-7-nitro-4-(2.2.2-trifluoroethvl)-2//-1.4-benzoxazme (Structure 24 of Scheme V. where R3. R4, R5. R7. R8 = H, R6 = Et. R13 = CHgCFQ: A solution of IsK) g (0.612 mole) of the crude (2£)-2-[2-fluoro-4-nitro(2,2,2- trifluoroethyl )anilino]-l-butanol in 1 Liter of dry THF was added dropwise to a stirred suspension of 36.77 g (0.919 mole, 1.5 eq) of sodium hydride in 1.5 L of dry THF under nitrogen atmosphere. After complete addition, the reaction mixture was refluxed for 3 h when TLC of the reaction mixture indicated complete conversion. After cooling to room temperature. 400 mL of methanol was added to destroy excess sodium hydride. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The organic portions were combined, washed with bnne and dried over MgSCAi. After filtration, the solvents were evaporated under reduced pressure. The crude product thus obtained was purified by silica gei column chromatography (ethyl acetate: hexanes 1:9) to obtain (+V(3/^)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2/f-1,4-benzoxazine as a yellow crystalline solid. Yield 71 g (40%). [a] D= + 56.6 (CHC13, c 7.8); JH NMR (CDC13) 6 7.SO (1H, dd, J = 2.56, 8.98), 7.71 (1H, d, J = 2.57), 6.72 (1H, d, J = 9.07), 4.34 (1H, dd, J = 1,44, 11.02), 4.12 (1H, m), 4.06 (1H, dd, J = 2.125 11.04), 3.79(1H, m), 3.37 (1 H. m), 1,68 (2H, m), 1.00 (3H, t, J = 7.54). 13C NMR: ppm 142.6, 139.1, 138.6, 126.1, 118.6. 112.6. 110.8, 64.9, 58.9, 50.6, 22.5 and 10.3. ('3^)-3-Ethvl-3,4-dihvdro-4-(2.2.2-trifluoroethvl)-7-(trimethvlacetarnido)-2/f-1.4- benzoxazine i Structure 26 of Scheme V. where R3. R4. R5. R7. R8 = H. R° = Et. R13 = CH?CFs._R° -" /-butyl'): A solution of 35 g (0.121 mole) 7-nitrobenzoxazine in 700 mL of ethyl acetate containing 3.5 g of 10% palladium on carbon was hydrogenated under ambient pressure. The reaction mixture was stirred for 12 h at room temperature. When TLC of the reaction mixture indicated complete conversion, 14.2 g (0.18 mol) of pyridine was added to the solution. After stirring for an hour, 17.4 g of tnmethylacetyl chloride was added dropwise to the reaction mixture and it was stirred for another 2 hours until TLC indicated the complete conversion. The reaction mixture was quenched with ice and the " organic layers were washed with sodium bicarbonate solution, 0.5 N HC1 and brine. The crude produc: thus obtained was subject to silica gel column chromatography (ethyl acetate: hexanes 1 :9) to afford the desired (3J?)-3-ethyl-3,4-dihydro-4-(2.2,2- tnfluoroethyi')-7-(tnmethylacetamido)-27/-l,4— benzoxazine as a white solid. Yield 35 g (84%). f a ] D= -24.0 (CHC13, c 1.5); 'H NMR (CDC13) 5 7.12 (1H, b), 7.04 (1H, d, J = 2.45), 6.97 (1H, dd, J =2.46, 6.2), 6.69 (1H, d, J = 8.66), 4.20 (1H, dd, J = 1.78, 10.77), 3.9t-> ( 1H, dd. J •= 2.22, 10.68), 3.81 (1H, m), 3.68 (1H, m), 3.14 (1H, m), 1.57(2H, m), 1.29 (6H. s), 0.^5(3H, U J = 7.48). 13C NMR: ppm 176.5, 144.3, 130.4, 129.7, 115.0, 1-14.3, 109.8. 65.0, 59.1, 53.8. 39.6, 27.9, 22.7,10.7. ( 3 )-j. - )- 3-Ethyl-3 ,4-di_hydro-8-(trifluQroacetyl)-4-(2,2r2-trifluoroethyl)-7- ('tnmetlivlacelamidgj-2/j-l,4-benzQxazme (Structure 27 of Scheme V. where RJ. R". R". R '. Rs - H, R6 -- Et, R13 = CHzCFi, Rb = /-butyl): A solution of 35 g (0.102 mol) of (37?)- 3 -erh y]-3 ,4-cl ih vdro-4-(2.2,2-trifluoroethyl)-7-(trimethylacetamido)-2//- 1 ,4-benzoxazine was disso ved in 800 ml. of dry ether under nitrogen atmosphere. The solution was then cooled to oO'T and 150 mL (1.7M in pentane, 0.255 mol) of 72-BuLi was added dropwise. [lie reacuon mixture was stirred at -30°C for one hour before it was allowed to warm to - 8°( '. The temperature of the reaction mixture was then maintained at -8°C to -5°C for 5 hours after which it was cooled down to -30°C. 57.9 g of ethyl tnfluoroacetate (0.408 mol) was then added to the reaction mixture and the solution was allowed to warm up to room temperature overnight. The reaction mixture was poured in to aqueous ammonium chloride and extracted with ether. The organic portions were combined, washed with brine, dried over MgSC>4 and evaporated under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography (ethyl acetate: hexanes 1 : 9) to provide 25 g (56%) of (3/?)-(-)-3-ethyl-3,4-dmydro-8-(trifluoroacetyl)-4-(2,2,2- tnfluoroethyi)-"7-(triinethylacetamido)-2//-l,4-benzoxazine. .4-dm l -benzoxazine (Structure 28 of Scheme V. where R3. R4. R:;: = CH?CF. Rb = r-butvl): A 1-L round bottom flask was charged with. 25 g (57 mmol) of (3/?)-(-)-3-ethyl-3,4-dihydro-8-(trifluoroacetyl)-4-(2,2,2- trifluoroethyl)-7-(trimethylacetamido)-2^-l,4-benzoxazine, 23.8 g (68.4 mmol) of (carbethoxymethylene)-triphenyl phosphorane and 500 niL of toluene. The solution was heated to reflux for 4-5 hours until TLC indicated that the starting material was gone. The toluene was evaporated and 500 mL of ether/hexane (1:1) was added to the crude product. The solution was then cooled down to -5°C for several hours and filtered. The filtrate was concentrated under reduced pressure and subject to silica gel column (ethyl acetate : hexane, 1 : 4 ) to afford 28.5 g (93%) (3J?)-S-[2-(l-carbethoxyprop-l-enyl)]-3-ethyl-3,4- dihydro-4-(2.2.2-trifluoroethyl)-7-(trimethylacetamido)-2H-l,4—benzoxazine as a brown oil. j u ir .24.4 (CHC13, c 20.1); JH NMR (CDC13) 5 8.83 (1H, b), 7.67 (1H, d, J = 01'i. 6.04 ( 1H, d, J - 8.99), 4.30 (1H, dd, J = 1.64, 10.80), 4.05 (1H, dd, J = 2.38, 10.82), 3.92 ( I L L m). 3,69 (Hi, m), 3.24 (1H. m), 1.59 (2H, m), 1.27 (6H, s), 0.96 (3H, t J = 7.38',, l:!C NMR: ppm 186.4, 177.4, 144.3, 129.9, 129.4, 129.3, 126.6, 123.8, 121.0, 120.3,, 119 -7, U7.4. 116.4, 114.6, 11.3.5, 111.7,65.6,58.6,52.7,39.9,27.7,22.8, 10.4. LMli i-Hthvl:;2_J,4;7-tetrahyd [L4jojvazijio 12.3--/]ciurnoiine-8-Qne (Compound 110, Structure 29 of Scheme V. where R1. R.L R'-. R: . K". R8 - H. R2 = trifluoromethvl. R6 = Et R13 = CHZCF2): 36 g (70.6 mmol) of (3A')-8-|2-('l-carbethoxyprop-l-enyl)]-3-ethyl-3,4-dihydro-4-(2,2,2-trifluoroethyl)-7- (TnniethvIacL-tam]do)-2f/-l,4-benzoxazme was dissolved in 761 mL of acetic acid and 5U ' ml.., of concentrated hydrochloric acid. The solution was heated to reflux for 12 hours until TLC indicated the complete conversion of the starting material. The reaction mixture was then allowed to cool to room temperature. The reaction was neutralized with cold aqueous NaOH solution to pH 6-7 and extracted with EtOAc. The combined organic solution was evaporated and purified by silica gel column. (Ethyl acetate: hexane 1:1) chromatographv and subsequent recrystallization from methanol to obtain 23 g of Compound 1 10 as a yellow solid. Yield: 86%. [a] D= -42.0 (EtOH, c 63.5); *H NMR tCDCl.-,) 3 12.9 (1H, b), 7.15 (1H, s), 7.13 (1H, d. J = 8.9), 7.05 (1H, d, J - 8.96), 4.37 (1H, d, J - 10.70), 3.97 (1H, dd, J = 2.04, 10.7), 3.84 (1H, m), 3.74 (1H, m), 3.23 (1H, m), 1.58 12H, m). 0.97 (3H, t, J = 7.52). 13C NMR: ppm 162.2, 139.5, 137.8, 133.9, 127.8, 125.:. 123."7, 121.9, 121.0. 1.09.7, 106.5,64.2,58.4, 55.1,22.9, 10.3. EXAMPLE 42 (±V2,3.4.7-Tetrahvdro-4-(2.2,2-tnfluoroethvlV3.10-bisrtTifluQromethvl)-8gf L4]p_xazino| 2,3:/lquinolin-8-one (Compound 141, Structure 29 of Scheme V, where R1, R , R'\ R:. R . ir = H, R-. R° = tnfluorom ethyl Ru = -CH;CF-Q 2-(2.2_.2-rri_nuojoethvl)ammo-S-m'tTOphenol (Structure 30 of Scheme VI. where KRllJI-JClisCFj); To a solution of 2-amino-5-nitrophenol (250 mg, 1.62 niniol) in 3 mL of tntluoro acetic acid stirred at 0°C, was added sodium borohydride (pellets, 375 mg, 9.91 mmol). The orange solution was allowed to slowly warm to rt and stirred for 12 h. The solution was diluted with 50 mL of water and cooled to 0°C. Solid potassium carbonate was then slowly added until the pH reached 7. The solution was extracted with ethyl acetate 12 x 1 00 mL) and the combined organic layers were washed with brine (25 mL), dried with anhydrous magnesium sulfate, filtered and concentrated to give an orange solid Flash chromatography (7:3 hexanes:EtOAc) afforded 0.32 g (S3%) of 2~(2,2,2- nifluoroethy])amino-5-nitrophenol, a yellow solid. JH NMR (400 MHz. acetone-d6) 9.4S (broad s, 1H). 7 79 (dd, 1H,.7 = 9.1, 2.4), 7.67 (d, 1H, J= 2.4), 6.96 (d, 1H, .7= S.S), 6.20 (broad s. !H). 4.26-4.18 (m, 211). (r.-)o.4-DihvdrQ-3-hydroxy-7-nilTo-4-(2.2.2-trifluproethyl)o-(triflupromethyl}-2//- i .4-beiizoxa7int: (Structure 24 of Scheme VL where R3, R4. R7. Rs = H. R5 = OH. R6 = tnfjuprornethy], R;;' — CH^CF^): To solution of 2-(trifluoroethyl)amino-5-nitrophenol (100 rag, 0.45 mrnol) and potassium carbonate (250 mg, 1.81 mmol) in 0.5 mL of dry dimethyformamide pre-heated to 65-75°C was added l-bromo-3,3,3-trifluoroacetone (0,28 mL, 2.70 inrnol) via a syringe purnp over 2 h. The crimson solution was then allowed to stir lor 2-3 hours at 65-75°C, then the solution was allowed to cool to room temperature, extracted with ethyl acetate (2 x 50 mL) and washed with brine (25 mL). The organic l.iyer was dried with anhydrous magnesium sulfate. filtered and concentrated under reduced pressure to give a brown oil. The crude oil was purified via flash chromatography (4:1 hexanes:EtOAc) to afford 97 mg (63%) of (±)-3,4-dthydro-3- hydroxy-7-mtro-4-(2.2.2-trifluoroethyl)-3-(triiluoromethyl)-2/f'-1.4-ben20xazine. JH NMR WOO MHz, CDC13) d 7.89 (dd, 1H5 J= 7.8,2.5), 7.80 (d, 1H, J = 2.5), 6.94 (d. 1H: J = :^.l). 4."1 ui. !H. J= 11.5). 4.51-4.63 (s, 1H), 4.08-4.12 (m, 1H), 4.00-4.06 (m, 2H). (-1-3.4- Dilivdro-7-nifro-4-(2.2,2-tnfluoroethyl)-3-(trifIuoromethvl)-2Ar-l .4- benzoxazme (Structure 24 of Scheme VI. where R3, R4. R'\ R7, R8 = H, R6 = sCFj}: To a solution of (±)-3,4-dihydro-3-hydroxy-7-uitro-4-" (2r2,2-trifluoroethyl)-3-(tTifJuoromethyl)-2H-l,.4-benzoxazine (0.10 g, 0.29 mmol) in 3 mL of trifluoroaeenc acid and then sodium cyanoborohydnde (3.0 g, 47.4 mmol) was slowly added via an solid addition funnel under nitrogen at 0°C over the course of 30 minutes the reaction was allowed to warm to rt and stirred for 12 hours. The reaction mixture was then diluted with water and cooled to 0°C. Solid potassium carbonate was then added slowly to p.H 7 The solution was extracted with ethyl acetate (2 x 100 mL) and the combined organic layers were washed with brine (50 mL), dried over magnesium sulfate, filtered and evaporated under reduced pressure to give an oil. The oil was purified via Hash chromatography (7:3 hexanes:EtOAc) to afford 51 mg (52%) of (±)-3,4-dihydro-7- nitro-4-(2,2.1!-tnfluoroethyl)-3-(trif]uoromethyl)-2//-L4-benzoxazine. JH NMR (400 MHz, CDC1-.) d 7.87 (dd, 1H, J= 9.1, 2.8), 7.81 (d, 1H, J= 2.5), 6.92 (d, 1H, J= 9.1), 4.7? (d. 111 ,/ =• 12.1), 4.48-4.39 (m, 1H), 4.13-4.06 (m, 2H), 3.99-3.88 (m, 1H). 'jEliT Amino-3,4-dihydrQ-4-(2,2.2-trifluoroethyl)-3-(trifluoromethyl)-27:Z-l,4- Ml»2x;iz IIICL i Structure 25 of Scheme V. where R3. R4. R5. R7. Rs = PL R6 = tJli]£^2mi^hvL.Rl'liLCH2CFj}: To a solution of (±)-3,4-dihydro-7-nitro-4-(2,2,2- n'iiiuoroethyi*-3-uritluoromethyl)-2//-1.4-beri2oxazine (100 mg, 0.30 mmol) in 1.5 mL erhyl acetate vvas added 10% Pd-C (42 mg). The reaction mixture was then purged with nitrogen and then purged with hydrogen. A hydrogen balloon was then inserted through a septum into trie reaction mixture and allowed to stir for 3 hours at room temperature. The solution was then filtered through a pad of celite and nnsed with ethyl acetate. The solvent was evaporated under reduced pressure to give a crude brown oil which was purified via flash drromatography (2:1 hexanes:EtOAc) to afford 85 mg (93%) (±)-7- amin.(}-3.4-dihydro-4-(2,2,2-tTifluoroethyl)-3-(trifluoromethyl)-2J:7-l,4-benzoxazine. ^i NMR (400 MHz, CDC13) 6.6S (d, 1H, ./= 8.4), 6.32-6.28 (m, 2H), 4.56 (dd, 1H, J= 12.0, 0.96), 4.16-4.00 (m, 2H). 3.84-3.69 (m, 2H), 3.60-3.32 (m, 2H). (±l-3,4Jj^ydro-4-(2,2._2-trifluoroet_hvl)-3-(trifluorornethyl)-7- (tnmethvlaceiamido)-2/7-1.4-benzoxazine (Structure 26 of Scheme V. where R\ R4. R3. R". Rlr- H. R: i = tiifltioromethvl R13 = CH2CF3. Rb = f-burvl): To a solution of (±)-7- anuno-3,4-dinyuro-4-(2,2.2-tnfluoroethyl)-3-(trifluoromethy})-2/7-l,4-benzoxazme (140 88 mg, 0.47 rnmol) in 5 mL EtOAc was added trimethylacetyl chloride (0.085 mL, 0.70 mmol) and anhydrous pyridine (0.056 mL, 0.70 mmol). The solution was allowed to stir at n for 12 h. The solution was then washed sequentially with saturated sodium bisulfate (2 \ } 0 mL), copper sulfate (10 mL) and bnne (10 mL). The organic phase was dried with anhydrous magnesium sulfate. filtered and the solvent was evaporated under reduced pressure to yudd an oil. The oil was purified via flash chromatography (7:3 hexanes:EtOAc) to afford 160 mg (89%) of (±)-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3- (tTilluoroinetliyl)-7-(tnmethylpropionamido)-2^-l,4-benzoxazine. ]H NMR (CDC13, 400 MHz) d 1 .25 is, 9H). 3.78 (sext, J = 8.0 Hz, 1H), 3.88 (m, 1H), 4.02 (m, 1H), 4.22 (sext. J - S.3 Hz, 1H), 4.59 (d, J - 11.6 Hz, 1H), 6.77 (d, J = 8.8 Hz, 1H), 7.05 (dd, J = 2.4 Hz, 8,8 Hz. 1 H). Til id, .) .-= 2.44 Hz, 1H), 7.15 (s, 1H). L-HJ: 3 , 4-TMiydrQrS-(trifluoroacetyl)-4-(2,2,2-lTifluQroethyl)-3-(trifluoromethyl')-7- (lDJBgth^la^iainidoV2-L4-benzoxazine (Structure 27 of Scheme V. where R3. R4. R3. RLi\;;j::±LJ L K° = tnfluoromethvl R13 = CH2CF^ Rb = r-butvl): To a solution of (±)-7- (2.2--diiaiethy.lpropionamido)-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)-2f/- L4~benzoxaz!ne (200 mg, 0.52 mmol) in 3 mL of dry diethyl ether at~30°C was added tbutvllitiuum « 1 ,7M; pentane. 0.80 mL, 1 .35 mmol) was added dropwise over of 30 mm and then stirr.rd at • • • ] 0°C. The deep yellow solution was allowed to stir at -10°C for 5-6 hours and then recooicd to -30°C and tnfluoroethyl acetate (0.1 S6 mL, 1 .56 mmol) was slowly added The reaction was allowed to gradually warm to room temperature over the course oi 12 nours. The reaction was quenched with saturated ammonium chloride (2 mL) and extracted with ethyl acetate (2 x 10 mL). The combined organic layers were washed with brine (p mL). dned over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to give a brown oil. The substrate was punfied via flash chromatography (-1- i hexanes.TitOAc) to afford 40 mg (15 %) of (=)-3,4-dihydro-8-(trifluoroacetyl)-4- (2,2.2-tnlluoroeihyl)-3-(trifliiorornethyr)-7-(trimethylacetarnido)-2F-l,4-benzoxazine. ]H NMR (400 MB/, CDC13) d 8.92 (s, 1H), 7.81 (d, 1H), 7.06 (d, 1H), 4.68 (d, 1H, J= 12). 4.224.3S (m. 1 H), 4.05-4.12 (m, IH), 3.93-4.20 (m, 1H), 3.78-3.91 (m. 1H), 1.28 (s, 9H). !iyiii?--itni^^ (Structure 28 of Scheme V. wilgre_BJJR:..R'iJRL BZ- RSJLH. R2. R6 = tnfluoromethvl R13 = CHoCF.. Rb = Nbutvl"): A solunon of (i )-3,4-diliydro-S-(trifluoroacetyl)-4-(2,2,2-tTifluoroethyl)-3-(trifluoromethyl)- 89 7-(trimethy!acetamido)-2ftr-lJ4-benzoxazine (40 mg, 0.08 mmol) and (carboxymethylene)triphenyl phosphorane (35 mg, 0.10 mmol) in 1 mL of dry toluene was heated at reilux for 5 h, whereupon the solvent was removed under reduced pressure to afford an oii. Flash chromatography (7:3 hexanes:EtOAc) afforded 18 mg (40%) of (±)-8- [2-(l-carbethoxyprop-l-enyl)]-3,4-dihydro-4-(2.2.2-trifluoroethyl)-3-(trijQuoromethyl)-7- (tnmethylacetamido)-2-L4-benzoxazine. JH NMR (400 MHz, CDC13) d 7.61 (d, 1H), 7.22 (s, 1 H). 6,92 (d, 1H), 6.30 (s, 1H), 4.62-4.71 (m, 1H), 4.25-4.34 (m, 1H), 4.05-4.10 (ni, 1HX 3.92-4.05 (m, 1H), 3.79-3.91 (m, 1H), 1.38 (t, 3H), 1.29 (s, 9H), 1.23 (q, 2H). (±)-2.3.4.7-Tetrahvdro-4-(2,2.2-tnfluoroethvn-3.10-bis(tnfluoromethvl)-S7Jr- 11.4|px_azin()f2,3-/lquiriQ_lin-8jione (Compound 141. Structure 29 of Scheme V. where R1. R\ R\ R\ R7. R8 - H. R2 = trifluoromethvl R6 = trifluoromethvl. R13 = -CHgCF^): A solution of (±)-8-[2-(l-carbethoxyprop-l-enyl)]-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3- (trifluoromethyl)-7-(trimethylacetamido)-2flr-l,4-benzoxazine (IS mg, 0.030 mmol) in 0.33 ml. of acetic acid and 0.20 mL of concentrated hydrochloric acid was heated at reflux for 12 h. Ethyl acetate (10 mL) was added and the solution was neutralized with 6 N sodium hydroxide until the pH reached n. The mixture was extracted with ethyl acetate (2 5 ml.) and the combined organic layers were dned with anhydrous magnesium sulfate, filtered arid evaporated under reduced pressure to give a greenish-brown oil. The crude pToauei was puniied via flash chromatography ( 1 :1 hexanes EtOAcj to afford 6 mg (42%) of Compound 141, a yellow solid, *H NMR (400 MHz, CDC13) 511.4 (broad s, 1H), 7.21 (JJ = °.2, 1H), 7.16(s. 1H). 7.00 (d, J = 9.2, 1H), 4.78 (d, AB, J = 9.0, 1H), 4.29-4.38 (m, 1H). 4.05-4.11 (m, IH), 3.90-4.05 (m. Iff). 3.83-3.93 (m, 1H). 90 EXAMPLE 43 (")-2.3.4.7-Tetrahvdro-4-(2.2.2-tnfluoroethyl)-3.10-bis(tnfluoromethvl)-8ff- Ll .41oxazino[2,3"/lquinolin-8-one (Compound 142. Structure (-)-29 of Scheme V, where R.LRJ.JJL4... R° R\ R8 !=_H, R2 = trifluoromethvl. R5 = trifluoromethvl. R13 = -CHoCFQ and (•M-2.3.4.:-'retrahvdro-4-(2.2.2-tnfluoroetbyl)-3.10-bis(tnfluoromethyl)-8^r- [j,4]ox_azmg| 2,3 -/lquinolin-8-one (Compound 143, Structure_(+)-29 of Scheme V. where R[=_R.:J Compound 141 (3 mg) was dissolved in hexanesnsopropanol was separated by chiral HP!.,C on a preparative Chiralpak AS column (20 x 250 mm) on a Beckman Gold HPLC with 14% ethanol:hexanes at a rate of 6.0 mL/min, to afford 1.2 mg each of Compound 142 and Compound 143. Data for Compound 142: HPLC (Chiralpak AS prep, 20 x 250 mm, 14% EtOH/hexanes, 6 mL/min) rR 22.5 min; [ct]D = -20 (c = 0.11, EtOH). Data for Compound 143: HPLC (Chiralpak AS prep, 20 x 250 mm, 14% EtOH/hexanes, 6 mL/min i /R 2,v,6 mm; [a]D = +15 (c = 0.12, EtOH). EXAMPLE 44 (i )-2,3,.4,7-Tetrahydro--3-(2,2,2_-:tnfluoro_ethyl)-1 Q-(tiifluoromethylV8/-/- [1.4.ox.;-izino[2,3-/1quinolin-S-one (Compound 144, Structure 9 of Scheme 11. where R1. JLViC. .±.11 JiI_:^.rnfluororrietbyL R' = 2,2,2-trifluoroethyl) 4!.4\4'-tnfluoro)-r-butoxy]-2~ kQpro^xvz^::llrj.fJuoromethyl)quinQline (Structure 7 of Scheme II. where R!. R3. R4. R;±JLJ1'-Z-tnli^iSSietfayL R" = 2.2.2-tnfluoroethvl'): This compound was prepared according to General Method 1 (EXAMPLE 1) from 6-bromo-5-hydroxy-2-isopropoxy-4- (tniTuoroniethyl)quinoline (0.086 g, 0.24 mmol), (±)-2-7vr-r-butoxycarbonylamino-4,4,4- trirluoro-1-butanol (0.12 g, 0.49 mmol), triphenylphosphine (0.13 g, 0.49 mmol), DIAD ( 0 . 1 ml. 0.49 mmol) and A'-methylmorpholine (0.09 mL) in THF (4 mL) to afford 0.061 g (43°o'i of f^-)-!i-bromo-5-[(2'-/-butoxycarbonylan:ino)-(4'.,4',4'-trifluoro)-r-butoxy]--2- isopropoxy-4-(tnfluoromethyl)qumoline as a tan solid. !H NMR (500 MHz, CDC13) 6 ".S 1 (d,.; - S.H, LH), 7.58 (d, J =• 9.3, 1H), 7.31 (s, 1H), 5.53 (m, 1H), 5.00 (bm, 1H), 4.41 (bm. Hi .. 4 . io (bra. 2H), 2.74 (bm, 2H), 1.46 (bs, 9H); 1.42 (s, 3H), 1.41 (s, 3H). 91 (±) o .4-Dihvdro-8-isoproDOXY-3-(2.2.2-trifluoroethvl)-10-(trifluoi-omethyD-2Jg- [1.4)oxazino|2.3-/1quinoline (Structure 8 of Scheme II. where R1. R3. R4. Rs. =H. R2 = trifluorom ethyl, Rb = 2,2.2-trifluoroetliyl'): This compound was prepared according to General Method 2 (EXAMPLE 1) from (±)-6-bromo-5-[(2'-;-butoxycarbonylamino)- (4\4\4"-trif]uoro)-r-butoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline (0.061 g, 0.11 mmol) in CH2C12 (2 mL) and TFA (2 mL) to afford 0.038 g (75%) of (±)-6-bromo-5-[(2'- amino-(4\4'.4'--trifluoro)-]'-butoxy]-2-isopropoxy-4-(trifluoromethyl)quinoline. H NMR (500 MHz, CDCb) 8 7.81 (d, J= 9.3, 1H), 7.58 (d, J= 8.8, 1H), 7.32 (s, 1H), 5.53 (m, 111), 3.91 (m, 2H), 3.85 (m, 1H), 2.57 (m, 1H), 2.24 (m, 1H), 1.65 (bs, 2H), 1.42 (d, J = 2.0, 3H), 1.41 (d,,/- 1.5, 3H). Tliis material (0.038g, 0.08 mmol) was earned on according to General Method 3 (EXAMPLE 1) by treatment with Pd2(dba)3 (1.5 ing), BIN A? (2 mg) and r-BuONa (11 mg, 0.12 mmol) in toluene (1 mL) heated at reflux to afford 0.025 g (79%) of (=)-3,4-dihydro-8-isopropoxy-3-(2?2,2-trifluoroethyl)-10- (tnfliioromeihyl )-2/7-[l,4]oxazmo[2,3-/]quinolme, a yellow solid. !H NMR (500 MHz, CDC13) n "A 1 ( d . . / = = 8.(:>, ] H), 7.20 (s, 1H), 7.04 (d, J= 8.9, 1H), 5.48 (m, 1H), 4.30 (dd, J- 10.". 3.i 1H). 4.11 (m, 2H); 3.95 (m. 1H), 2.41 (m, 2H). 1.39 (s, 3H), 1.38 (s,3H). i^ii2,3.4.7-Tetrahvdro-3-(2.2.2-tnnuoroethvlV10-(trifluoromethvlV8/f- U irLL^xa/iin^iJ.- .-\-/lg.uinoiin-8-one (Compound 144. Stmcture 9 of Scheme II, where R', !l.a_Bl-Ji^i± H; 'R~; = tnfliiorornethyl. R" = 2,2.2-trifluoroethvl): Compound 144 was prepared according to General Method 4 (EXAMPLE 1) from (i)-3-ethyl-3.4-dihydro-8- isopropoxy-?-(2.2.2-trifluoroethyl)-10-(trifluorornethyl)-2//-[L4]oxazino[2,3-/]quinoline (S mg, 0.02 mmol) in cone. HC1 (1 mL) in AcOH (1 mL) heated at 90°C to afford Compound 144, a. yellow solid. lll NMR (500MHz, CDC13) 511.91 (bs, 1H), 7.14 (s, 1 H). 6.94 (S, 211), 4.31 (dd. /= 10.7, 2.4, 1H), 4.08 (m, 1H), 4.05 (bs, 1H), 3.92 (m, 1H), 2.38 (m, 2H). 92 EXAMPLE 45 (±)-2.3.4J-Tetrahvdro-4-methvl-3-(2,2.2-tnfluoroethvlV10-(trifluoromethvl)-8JgrL41oxazmp[ 2;3-r1quinolip-8-one (Compound 145, Structure 11 of Scheme II, where R1. R ;. R4. R::. R :'. Rs =•-- H. R2 = trifluoromethvl. R6 = 2.2.2 -tnfluoroethvl. R13 = CH^ L±V3.i4_-[;)ibvdrQ-8-isopropoxv-4-methvl-3-(2,2,2-tiifluorQelhyl)-lQiliifluoi ornet !ivlV2tf:1[1.41oxazmo[23-/1quinolme (Stmcture 10 of Scheme II, where R!. R:. R\ R'. R ' . Rs = H, R2 = trifluoromethvl. R6 = 2.2.2-trifluoroethyl. R13 = CHV). This compound was prepared by General Method 5 (EXAMPLE 1) from (±)-3,4-dihydro-8- is (0.025 g, 0.06 rnmol), paraforaialdehyde (0.02 g, 0.6 mmol) and NaCNBH3 (0.04 g, 0.6 mmol) m 2 niL glacial acetic acid to afford 0.017 g (65%) of (±)-3-ethyl-3,4-dihydro-8- isopropoxy-4-methyl-3-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-2//'-[l,4]oxazino[2,3- /Iquinolme. of sufficient purity as to be used directly in the next reaction. \H NMR (500 MHz, CDCl : » "48 (d, J= S.S, 1H), 7.22 (d,J = 9.3, 1H), 7.21 (s, 1H), 5.49 (m, 1H), 4.37 (d,J - 10.7, 1H), 4.08 (d, J= 10.7. 1H), 3.68, (m, 1H), 3.05 (s. 3Hj, 2.40 (m, 2H), 1.39 (d, J - 6.3, m\ 1..38 (d,./=6.3, 3H). M...4Jpx;j/inoi.2.3-/:lquinQlin-8-one (Compound 145, Stmcture 1 1 of Scheme II. where R1. E'L.R.1. RL.K ; R!:^ H,..R- = influoromethyl. R° = 2,2.2-tnfluoroethvi. Ri: = CHa) : C'ompound 145 was prepared according to General Method 4 (EXAMPLE 1) from (±)- 3,4-dihydro-S-isopropoxy-4-methyl-3-(2;2.2-trifluoroethyl)-10-(trifluoromethyl)-2J!:/- [ 1 ,4]oxazmo|2,3--/jqmnolme (0.017 g, 0.04 inmol) in cone. HC1 (1.5 mL) in AcOH (1.5 mi,] heated at %°C to afford Compound 145, a yellow solid. 'H NMR (500 MHz.. CDC13) 12,52ibs. ; H > . 7.1 6 (sr 1H), 7.06 (d. /= 9.3, 1H), 7.04 (d, J= 9.3. 1H), 4.3S (dd, J = 1 1 23, 2.0. i ;i), 4.1 ] (d, J = 5.4, 1H), 3.67 (m, 1H), 3.00 (s, 3H), 2.38 (m, 2H). EXAMPLE 46 (±)-4-Ethvl-2.3,4J-tetrahvdro-3-('2.2,2-trifluoroethyl)-lQ-(trifluoromethvD-8grL4] oxazinor2.3-/1quinolin-8-one (Compound 146. Structure 11 of Scheme II, where R1. R-\ R4, R5. R7. Rs = H. R2 = trifluoromethvl. R6 = 2.2.2-trifluoroethvl, R13 = Et) (rh)-4-Ethyl-3,4-Dihydro-8-isopropoxy-3-(2,2.2-tri£luoroethvl)-10- (•.nfluoromethvlV2//-['1.4]oxazino|'2,3:/]quinoline (Structure 10 of Scheme II, where R1. Kll Jill'L R8 = H. R- = trifluoromethvl, R6 = 2.2.2-trifluoroethvl, R13 = Et): This compound was prepared by General Method 5 (EXAMPLE 1) from (i)-3,4-dihydro-Sisopropoxy-. 5-r2.2,2-trifluoroethyl)-10-(tnfluoromethyl)-2//-[l,4]oxazino[2,3-/lqumoline (0.01.9 g, 0.05 mmol) and NaBH4 (0.5 pellets, >0.5 mmol) in 2 mL glacial acetic acid to afford (n)-4-etliyl-3,4-dihydro-8-isopropoxy-3-(2.2,2-trifluoroethyl)-10-(trifluoromethyl)- 2H 1.4|oxa/,ino[2,3-;]quinoline. of sufficient purity as to be used directly in the next reaction. (---)-3-Ethvl-213,4,7-Tctralwdi-o-3-(2,2.2-trifluoroethvlVlQ-(trifluoromethylV8ffj 1,4]oxazino|'2.3-/]qumolin-8-one (Compound 146. Stiiicture 11 of Scheme II. where R1, BI•. KLR'\ F:'". RM = H. R; = trifluoromethvl R6 = 2.2.2-trifluoroethvl R13 = Et): (..'ornpound 146 was prepared according to General Method 4 (EXAMPLE 1) from (±)-4- ct.hy!-3,4-dihy(iro-S-i.sopropoxy-3-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-2//- 1,4]oxazino|2,3-/]quinoline m cone. HC1 (2.5 mL) in AcOH (2.5 mL) heated at 90°C to afford Compound 146, a yellow solid. :H NMR (500MHz, CDC13) 5 11.97 (bs, 1H): 7.15 (s. 1H). -.06(d, .7 = 9.3, 1H), 7.01 (d;./=8.8, 1H), 4.38 (dd,/= 1.0, 10.7, 1H), 3.88 (d, J = 1 1 2, IK), 3 . 7 1 (m. 1H). 3.47 (m, 1H). 3.25 (m, 1H), 2.41 (m, 1H), 2.2S (m, 1H), 1.22 (t, J= 7.3. 3H). 94 EXAMPLE 47 (±)-2.3,4,7-Tetrahydro-3,4-bis('2,2.2-tTifluoroethvl)-10-(trifluoroniethvD-8^'- ( L4|oxazinoj2.3~/lquinolin-8-Qne (Compound 147. Structure 11 of Scheme II. where R . R R4. R\ R '. Rs =.H. R2 = tnfluoromethyl. R6 = 2.2.2-tnfluoroethyL R13 = 2.2.2- tnfl U Lr:.bl: 4-pihYdro-8-isopropoxv-3.4-bis(2.2.2-trifluoroethvl)-lQ-(trifluoromethyl)- 2H-\ 1 ,4|oxazmo(2.3-/1gmnolme (Structure 10 of Scheme II. where R1. R3. R4. R5. = H. R2 = 2.2 2-tnfluproethvl R13 = 2.2.2-trifluoroethyl): This compound was prepared by General Method 5 (EXAMPLE 1) from (±)-3,4-dihydro-8-isopropoxy- 3.4-bis(2,2,2 tnfluoroethyl)-10-(tnfluoromethyl)-2H-[l,4]oxazmo[2,3-/]qumolrne(0.02 g, 0.05 mniol) iind NaBH4(0.5 pellets, >0.5 mmol) in 4 mL trifluoroacetic acid to afford 0.02 g (83% i 01 (±)-3,4-dihydro-8-isopropoxy-4-methyl-3,4-bis(2,2,2-trifluoroethyl)-10- (InfluoromeUiyi )-2//-[l,4]oxazino[2,3y]quinoline, of sufficient punty as to be used directly in th<..x next reaction> 1 '=_• 3,--kj:IetrahYdro-3,4-bis(2_r2:24rifliioroeUiyl)-lQ-(1rifluoromethyl)-8//- U ^ A1 R . Rl.R:l:::. H. R- = trifluoromethyl. Rb = 2.2.2-mfluoroethvl R13 = 2.2.2-trifluoroethyl): Compound 147 was prepared according to General Method 4 (EXAMPLE 1) from (±)- 3-4-dihydro-;s-isopropoxy-4-methyl-3-(2,2,2-tritluoroethyl)-10-(trifluoromethyi)-2j!;/- L4]oxi.t:inoi2,3'-/]qumolme (0.02 g, 0.04 mmol) in cone. HC1 (2 mL) in AcOH (2 mL) heated at 90CC to afford 12 mg (67%) of Compound 147, a yellow solid. 'H NMR (500 MHz. CDClo 1 2.57 (bs, IH), 7. IS (s, 1H), 7.17 (d, J= 8.8, 1H), 7.08 (d, ,/= 8.S, 1H), 4.44 (dd. ,/= 10.7. 1 .0, ]H), 4.06 (m, IH), 3.96 (m, IH), 3.79 (m, IH), 3.73 (m, IH), 2.38 (m, 2H). EXAMPLE 48 (-1-2.3 A7-Tetrahvdro-3 .4-bisf2.2.2-trifluoroethvI)-l 0-(trifluoromethvI)-S/i- [I14|oxazinoj213-/|quinoim-8-one (Compound 148. Structure 11 of Scheme II, where R1. R3. .R4. R.\ = H, R2 = trifluoromethvl R6 = 2.2,2-trifluoroethvl. R13 = 2.2.2-tnfluoroethyl). +V [1 ,4]oxazino! 2.3-/]quinolin-8-one (Compound 149, Structure 11 of Scheme II. where R'. R ;. R4. R:i. = H. R2 = tnfluoromethvl. R6 = 2,2.2-trifluoroethvl R13 = 2.2.2-tnfluoroethvl) Compound 147 (12 mg) was dissolved in hexanes:ethanol was separated by chiral H.PLC on a preparative Chirapak AS column (20 x 250 mm) on a Beckman Gold HPLC with 86% hexanes:ethanol at a rate of 7.0 mL/min, to afford 6 mg each of Compound 148 and Compound 149. Data for Compound 148: HPLC (Chirapak AS prep, 14% EtOH/hexanes, 7 mL/min) rR 25.6; 'cc]D =-35.9 (c = 0.30, EtOH). Data for Compound 149: HPLC (Chiraipak AS prep, 20 x 250 mm, 14% EtOH/hexanes, 6 mL/min) /R 64.1 mm; [a D = "34.6 (c = 0.31, EtOH). EXAMPLE 49 (Eihi Q^cio^ropvlmethvl-2,3.4,7-tetrahvdro-3-(2,2.,2-trifl'uoroethvl)-10- LVUtUtQIQIDJLtQyJl-S/jiLl-41oxazino[23"/]quinolin-8-one (Compound 150. Structure 11 of Scheme II, where R'. R:i. R\ R5. = H, R3 = tnfluoromethvl. R6 = 2.2.2-trifluoroethvl. R13 = cyclopropy 1m ethyl) Compound 150 was prepared by General Method 5 (EXAMPLE 1) Compound 144 (0.02 g, 0.06 rnrnol), cyclopropylmethylcarboxaldehyde (0.05 mL, 0.6 rnmol) and NaCNBH? (0 036 g, 0.6 mmol) m 1 mL glacial acetic acid and 3mL methanol to afford Compound 150. ;H NMR (500 MHz, CDC13) 12.55 (bs, 1H), 7.20 (s, 1H), 7.17 (d.. 7= S.n. 1H), 1.0- (d,. 7 = 9.2, 1H), 4.41 (dd,J=10.7, 1.2, 1H), 4.01 (d, 7=9.2, 1H), 3.89 (m, 1H), 3.35 (dd, J - 15.0, 6.1, 1.H), 3.04 (dd, 7= 14.7, 6.7, 1H), 2.34 (m, 2H), 1.04 (m, 1H), 0.61 (m.2H). 0.25 (m,2H). EXAMPLE 50 (3R )-4 -C vcloprop ylmethyl-3 -ethyl-2,3.4.7-tetrahydro-10-(trifluorornethyl)-8#- [L41oxazmo[2,3-f1quinolin-8-one (Compound 151. Structure 11 of Scheme II. where R1, R; . R4, R'\ = H, R2 = trifluoromethyl Rb = ethyl R13 = cyclopropylmethyl) Compound 151 was prepared by General Method 5 (EXAMPLE 1) Compound 107 (0.01 5 g, 0.05 mrnol), cyclopropylmethylcarboxaldehyde (0.05 mL, 0.5 rnniol) and NaCNBH-, (0.032 g, 0.5 mmol) in 1 mL glacial acetic acid and 3 mL methanol to afford Compound 151. JH NMR (500 MHz, CDC13) 5 12.23 (bs, IH), 7.15 (d, J= 8.9, IH), 7.13 (s, IH), 6.9S 3.37 (dd, J- 14.6, 5.8, IH), 3.34 (m, IH), 3.00 (dd, J= 15.0, 7.0, IH), 1.55 (m, 2H), 1.03 (m, IH), 0.97 a. y = 7.6, 3H), 0.57 (m, 2H), 0.23 (m, 2H). EXAMPLE 51 (37? )-4-( 2-Chloroethyl)-2,3 A7-tetrahvdro-3-isopropyl-l 0-ftrifluoromethyl)-S/jr- [1.4|oxazino| 2.3-/1quinolin-8-one (Compound 152. Structure 11 of Scheme II, where R1, R-\ R:'. R5, = 1:1. R2 = trifluoromethvl. R6 = isopropvl. R13 = 2-chloroethyl) (Compound 152 was prepared according to General Method 5 (EXAMPLE 2) from (3A>)-3.4-dihydr()-8-isopropoxy-3-isopropyl-10-(trifluoromethyr)-2//-[L4]oxazino[2,3- ] i n n o i i i i e ( l o rug, 0.05 mmol) and NaBH4 pellets (>10 equiv) in 0.5 g chloroacetic acid to afford 1 1 mg(5S%) of (3/?)-4-(2-cbJoroethyl)-3,4-dihydro-8-isopropoxy-3-isopropyl- 10-(trifluoromethyl)-2H-[l,4]oxazino[2,3-/|ciuinolme. This material (11 mg, 0.03 mmol) was earned on according to General Method 4 (EXAMPLE 1) by treatment with 4 mL of 1: i acetic acid concentrated HC1 (0.02M) heated at 90°C for 4 h to afford Compound 152. 'H NMR (500 MHz, CDC13) 12.06 (bs, IH), 7.13 (s, IH), 7.12 (d, J= 8.8, IH), 6.98 (d, J - 8.8, 11T). 4.53 (dd, J= 10.7, 1.5, IH), 3.88 (dd, J= 10.7, 2.4, IH). 3.82 (m, IH), 3.71 (m, IH'); 5.63 un. IH), 3.49 (m, IH), 2.93 (m, IH), 1-82 (m, IH), 0.99 (d, ,7= 10.3, 3H), 0.9cS (d, y= 10.3, 3H). EXAMPLE 52 (±)-23,4;7-Teti-ahvdro-2-methvl-4-(2:2.2-trifIuoroethvlVlO-(trifluoromethvlV8ff- [L4]oxazi;nQL2..^./1qumoliD-8-one (Compound 153. Structure 11 of Scheme II. where R1. E^JHRVl H. R2 = trifluoromethvl R: = Me, R13 = CtfrCFV) (:i )-6--Bromo-5-[( 1 '-f-butoxycarbonyjamino)-2'-propoxyl-2-isopropoxy-4- LkoJIuQTQnigtljY.Llg.uinoline (Structure 7 of Scheme II. where R!. R4. R'. R6. = H, R2 - trifliiorornethyj. RJ = Me): The compound was prepared according to General Method 1 (EXAMPLE I ) from 6-bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinoline (0.1 g, 0.3 mmol). (=)-1-A/'-t-butoxycarbonyl-2-propanol (80 mg, 0.5 mmol), triphenylphosphine (120 mg, 0.5 mmol) and diisopropyl azodicarboxylate (0.09 ml, ().:> mmol) in 0.12 mL ,'V-methylmorpholme in 3 mL dry THF to afford 145 mg (63%) of (:~)-t>-brorno-.5-| 1.1 '-/-butoxycarbonylammo)-2'-propoxy]-2-isopropoxy-4- (trirluoTOmethyl)qumoline alter flash cliromatography (4:1 hexanes/EtOAc). ]H NMR (500 MHz, n:)n:f) o 7.7f) (d,/=9.3, 1H), 7.51 (d, .7=8.8, 1H), 7.27 (s, 1H), 5.53 (m, 1 Hi. 5.12 (m. 2H). 3.57 (m, 1H), 3.28 (m, 1H), 1.46 (s, 9H), 1.43 (d,J= 8.3, 3H), 1.42 (d, ./ =!s.3. 3ti). ' ) . ( i 2 (d, J=6.3, 3H). 1:!;;.Hh Biomo--5-(r-amino-2'-propoxv)-2-isopropoxv-4-(trifluoromethyl)quinoline: This compound was prepared according to General Method 2 (EXAMPLE 1) from (i)-6- bromo-5-j(3'-.f-butoxycarbonylamino)-2'-butoxy]-2-isopropoxy-4- (trii]uoromeLhyl)quinoline (91 mg, 0.2 mmol) in 2 mL CH2C12 and 2 mL TFA to afford 86 mg (100%) o;'(:-.• )-6-bromo-5-(l '-amino-2'-propoxy)-2-isopropoxy-4- (triiliiororaechyDqumoline. 'H NMR (500 MHz, CDC13) 5 7.77 (d. J= 8.8, 1H), 7.53 (d, J = S.S, 1H), T27 (s, 1H), 5.52 (m, 1H), 5.21 (m, 1H), 3.20 (m, 2H), 1.42 (d, J= 10,3, 3H), 1.41 (d. 7 - 1 0,3. 3H), 0.93 (d, J= 6.3, 3H). (4.hl;4rJJihydro-S-isopropoxy-2-methyl-10-(trifluoromethyl)-2/:/'-[l,41oxa2ino[2.3- /lumsolmeiStnicture 8 of Scheme II. where R , R . R , R°. = H. R' = trifluoromethvl. R rMi'j: This compound was prepared according to General Method 3 (EXAMPLE 1) from (.i i-6-bromo-5-( 1 '-ammo-2l-propoxy)-2-isopropoxy-4-(trifluoromethyr)quinoline (S6 mg, 0.2 rnim.il), (- }-2.2'-bis(diphenylphosphino)-l,r-binaphthyl (5 mg), Pd2(dba)3 (4 mg), sodium z-butoxide (28 mg, 0.3 mmol) to afford 9 mg (14%) of (±)-3,4-dihydro-8- isopropoxy-2 - methyl-10-( tnfluoromethyl)-2H"-[ 1,4]oxazino[2,3-/] quinoline, after 98 purification by flash chromatography (4:1 hexanesrEtOAc). !H NMR (500 MHz, CDC13) 5 7.35 (d,,/ = 8.8, 1H), 7.18 (s, 1H), 7.04 (d, J= 8.8, 1H), 5.48 (m, 1H), 4.23 (in, 1H), 3.82 (m. HI), 3.47 1.39(d,./--=C>.3, 3K), 1.38 (d,y=6.3, 3H). c-i:)-3..4-Dihvdro-8-isopropoxv-2-methyl-4-(2,2,2-trifluoroethyl)-10- (i?iflupromethyri-2//-|'l,41oxazmor2,3-/1qumoline (Structure 10 of Scheme II. where R1, R'. R:\ R(\ --- li, R2 = trifluorornethvl R3 = Me, R13 = CHgCF-Q: This compound was prepared according to General Method 6 (EXAMPLE 3) from (±)-3,4-dihydro-Sisopropoxy- 2. methyl-10-(tniluoromethyl)-2/i-[1.4]oxazino[2,3-/]quinolme (9 mg, 0.03 mmol) and NaBli4 pellets (>10 equiv) in 1 mL trifluoroacetic acid to afford 8 mg (73%) of (±)-3.4-dihydro-8-isopropoxy-2-methyl-10-(trifluoromethyl)-2J?:/'-[l,4]oxazino[2,3- /Iqinnoline, which was carried on without purification. (_:= )-2.3 A 7-Teffahydrp-2-methyl-4-(2,212-trifluQroethyl)_-1 Q-(trifluoromethyl)-8//'- |'L4]oxazmo|2,3-/]c]:uinQlin-8-one (Compound 153. Structure 11 of Scheme II. where R!, R4. R.:. R6. = li. R1' := trifluoromethyl, R3 ••= Me. R13 = CHaCFQ: (."ompound 153 was prepared by General Method 4 (EXAMPLE 1) from (±)-3,4- dihyd]'o--isonropoxy-2-methyl-10-(trifluoromethyl)-27:/-[l,4]oxazmo[2,3-/]quinoline (8 mg. 0.02 minor) in 4 mL of a 1 • I acetic acidiconcentrated HC1 heated at 90°C for 4 h to afford Compound 153. !H NMR (500 MHz, CDC13) 11.68 (bs, IK), 7.14 (s, 1H), 7.08 (d, •-• S.ll 1.1-T). c.94 (d, ./= l-».3, 1H), 4.24 (m, 1H), 3.88 (m, 1H), 3.78 (m, 1H), 3.44 (dd, ./ = 11 ". .1.4, IFh. 3.29 (dd, J= 11.7, 8.8, 1H), 1.45 (d,/= 6.3, 3H). EX4JVIPLE 53 Ql'Qr.l -Ethyl-4-(2-hydroxy-2-methvlprQpyl)-2.3,4,7-tetrahvdro-10- jtnfiuon)methvl)-S//-j 1.41oxa2ino|2.3-/1quinolin-8-one (Compound 154. Stnicture 11 of Scheme II, where R1. R3. R4. R5, R7. R8 = H. R2 = tnfluoromethvl R6 = isopropvl. R13 = 2-hvdroxy-2-methylpropyl) (3_^i-3-Ethyl-4-_(2-rnethyl-2-propenyn-3.4-dilivdro-8-isoprgpoxy-10- (tnfluoroiuejhyr)--2ff-[1.4_]oxazino|2.3-f)qumoline: This compound was prepared by treatment of (3^?)-3-ethyl-3,4-dihydro-8-isopropoxy- 10-(trifluorometh.yl)-2/:f- [ 1.4joxazino[2,3-/]quinoline (20 mg, 0.059 mmol), 2-methallyl bromide (40 mg, 0.30 mmol i and K CD, (41 mg, 0.30 mmol) in 1 mL DMF heated at 50 °C for 16 h. The 99 reaction was treated with an additional 2-methallyl bromide (60 mg) and was heated overnight at 50 °C. The mixture was extracted with ethyl acetate (2 x 25 mL), and the combined organic layers were washed with water (25 mL), brine (25 mL), dried over MgSO4- filtered, and concentrated afford 20 mg (87 %) of (3^)-3-ethyl-4-(2-methyl-2- propenyl)-3.4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2J?:r-[l,4]oxazmo[2,3:/]quinoline after flash cJiromatography (9:1 hexanes:EtOAc). JH NMR (400 MHz, CDC13) 5 7.39 (d, ./-9.0. 1 H ) . 7 l S ( s , 1H), 7.12 (d, ,7=9.0, 1H), 5.47 (septet, J= 6.2, 1H),4.91 (broads, 2H), 4.33 ( d d , . / - 10.7, 2.1, 1H), 3.96 (dd, J= 10.7, 2.6, 1H), 3.85 (d,AB,J= 17.1, 1H), 3.80 (d, ,1/9,./ •-- 17.1, 1H), 3.20-3.26 (m, 1H), 1.79 (s, 3H), 1.58-1.6S (m, 2H), 1.38 (d, J = 6.2, 311), 1.31 id. J = 6.2. 3H), 0.96 (t. ./= 7.4, 3H). (3_}; 3_-ljtliyl-4-(2-hydroxv-2-methvlpropvl)-2.3,4,7-tetrahydrp-1Q- (irrfluoromeihvl)-8//-[1.41o.\:azino[2^.3:/]quinolin-8-one (Compound 154, Structure 11 of Scheme II. where R1. R3, R4, R5. = H. R2 = tnfluoromethvl R6 = isopropvl. R13 = 2- lLYJi™xJ^2^i lejhylDrpjrylj: This compound was prepared by General Method 4 (EXAMPLE 1 ) with some modifications. A. solution of (3^)-3-ethyl-4-(2-methyl-2- propenv] i-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2//'-[l.,4]oxazmo[2,3-/Jquinoline ( i 1 me, P.02S mrnol) was heated in 1 mL concentrated HC1 at 75 °C and afforded 3 mg :-(]C) of Compound 154 after sequential column chromatography (9:1 CH^CLiMeOH) and preparat;vr HPLC (CDS semi-prep column, 20 x 250 mm, 65% MeOH/water, 3 niL/rnin) 'll NMR (400 MHz, CDC13) 6 11.4 (broad s, 1H), 7.26 (d, J= 8.9. 1H), 7.10 (s, IH'i. 6. S o t d. ,7 = 8.9, 1H), 4.40 (d, J= 10.3, 1H), 4.06 (broad d, ./= 10.3, 1H), 3.29 (d, AB, J = 15.0. 1H), 3.20-3.30 (m, 1H), 3.10 (d, .45, J= 15.0, 1H), 1.99 (s, 1H), 1.33 (s. 3H), L30(s. 3H), O.')7(t,y=7.4, 3H). EXAMPLE 54 Q R}- 2J.lJ-Tetrahydro-3-isobutvl-4-(2.2,2-rTifluoroethvl)-10-(trifluoromethyl)- S/iLL4loxa:',inol2.3-/lquinolin-S-one (Compound 155. Structure 17 of Scheme III, where Rl.E."lEi,_R '- R7. R8 = H. R2 = trifluoromethvl. R6 = isobutvl. R13 = CH^CF^ L=R1:.2.-(2iFluqro-4-nitrophenvl)amino-4-methvl-l-pentanol (Structure 21 of Scheme V. where R\ Rj. R5:. R5. R7. R8 = H. R6 = isobutvl): This compound was prepared according to the procedure described in EXAMPLE 41 (Structure 21 of Scheme Y.i from .:..4-,liJluoronitrobenzene (8.73 g, 54.9 mmol), ^-2-amino-4-methyl-l-pentanol (5.00 g, 42.7 mmol) m EtOH heated at reflux for 16 h to afford 6.0 g (55%) of (2J?)-2-(2- fluoro-4-nitrophenyl)amino-4-methyl-l-pentanol, a yellow solid, after flash chromatographv (gradient elution, hexanes:EtOAc 9:1 to 1:1). Data for (2JR)-2-(2-fluoro- 4-nitrophenyl)amino-4-methyl-l-pentanol: Rf 0.3 (3:1 hexanes:EtOAc); 'H NMR (400 MHz, CDCKio 8.01-7.97 (ra, 1H), 7.90 (dd, 1H, J= 11.7, 2.7), 6.74 (dd, 1H, .7=8.6, 8.6), 4.62-4.57 (m, 1H), 3.82-3.74 (m, 1H), 3.75-3.62 (m, 2H), 1.77-1.65 (m, 1H), 1.61- 1.45 (m, 2H). 0.99 (d, 3HT J = 6.6), 0.93 (d, 3H, J= 6.6). (4..51:. H 2-Flnoro-4-mtrQphenvl)-4-isobutvl-2-(trifluoromethyI)-1,3-oxazolidine (Structure 22 of Scheme V, where R3. R4. R5. R7, R8 = H. R6 = isobutvl. RA = tnfluorOTneth_yl): This compound was prepared according to the procedure described in EXAMPLE 41 (Structure 22 of Scheme V) from (2^)-2-(2-fluoro-4-nitrophenyl)amino-4- merhvl-1-pentano] (6.0 g, 23 mmol) trifluoroacetaldehyde ethyl hemiacetal (30.4 g, 211 nurtol) and/' loluenesulfouic acid (0.020 g, 0.10 mmol) in 250 mL benzene to afford 5.15 g i o5%) of (4A')-3-(2-fluoro-4-nitrophenyl)-4-isobutyl-2-trifluoromethyloxazolidme. Data for (4/v)-3-(2 -fluoro-4-nitrophenyl)-4-isobutyl-2-trifluoromethyloxazolidine as a mixture oiMiastereoniers: Rf 0.8 (3:1 hexanes:EtOAc); JH NMR (400 MHz, CDC13) 5 8.03-7.94 (m. 21T). o.9 .-: 4.7^ 4.45-4.40 (m, 1H, minor diast). 4.36-4.28 (m, 1H, major diast.), 4.11-4.01 (m, 2H), I .32-1.74(m. 1H), 1.66-1.52 (.in, 2H), 1.02 (d, 3H, major diast.,/= 6.4), 0.99-0.95 (m, 3H). 0.9i (d, 5H, minor diast.. .7 =6.6). (2/Q-2-12-FluorQ-4-nitrg(2,2.2-tiifluoro_ethyl)anilmo]-4-rnethyl-l-pentanol (StructureJl of Scheme V. where R3. R4. R5, R7, R8 = H. R6 = isobutvl, R13 = CH2CFQ: To a solution of (47?)-3-(2-fluoro-4-nitrophenyl)-4-isobutyl-2-tiifluoromethyloxazolidine (4.8 g, 14.3 mmol) and Et3Sitl (21.6 g, 186 mmol) in 60 mL chloroform was added BFjOEt; {'14 2, 60 inmol. added in portions) The reaction was heated at reflux for 1 d After cooling, the reaction was poured in water (200 mL) and extracted with chloroform ('" x 150 ml, i. The organic layers were combined, washed sequentially with water (200 mL) and bnrie (200 mL). dried (MgSO4), filtered, and concentrated under reduced pressure to a brown oil. Flash chromatography (gradient elution, hexanes:ethyl acetate 95:5 to 3:1) afforded 2.1 g (44%) of (2J?)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]- 4-methyl-i-penianol, an orange oil. Data for (2J?)-2-[2-fluoro-4-mtro(2.2.2- tnfluoroethyi)amlino]-4-methyl-l-pentanol: RfO.S (3:1 hexanes:EtOAc); JH NMR (400 MHz, ( Cl-0 r> 7.98 (dd, 1H, J= 9.3, 2.4), 7.94 (dd, IH, J- 12.9, 2.5), 7.40 (dd, 1H, J= 8,7, 8.7), 4.21-4,10 (m, 1H), 3.89-3.78 (m, 1H), 3.79-3.65 (m, 3H), 1.96-1.89 (m, 1H), i .07-1.54 (iii. I HI ] .55-1.44 (m, 1H), 1.32-1.22 (m , 1H), 0.91 (d, 3H, /= 6.6), 0.77 (d, 3H J - 0.6). (J..7v_l: 3.4-D]hydro-3-isobutvl-7-mrro-4-(2,2.2-trifluoroethvl)-2Ar-1.4-benzoxazine (Structure 24 of Scheme V. where R3, R4. R.s. R7, Rs = H, R6 = isobutvl R13 = CHZCF3_): This compound was prepared according to the procedure described in EXAMPLE 41 (Structure 24 of Scheme V) from (27?)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)aaiilino]-4- methyl-1 -pentanol (1.95 g, 5.76 mmol) in 30 mL THF and NaH (1.4 g, 35 mraol) in 25 ml. THF heated at reflux for 1 hr to afford 0.87 g (50%) of (37?)-3,4-dihydro-3-isobutyl-7- nitrO"4-(2,2,2-tnfluojroethyl)-277-l ,4-benzoxazine, a yellow oil. Data for (3J?)-3,4- d i hydro - 3 - isi ibutyl- 7-nitro-4-(2,2,2-trifluoroethyl)-2Jf/'-1,4-benzoxazine: Rf 0.6 (3:1 hexanes:HtO A C K 'H NMR (400 .MHz, CDC13) 5 7.79 (dd, 1H: ./= 9.1. 2.7), 7.71 (d, Hi J = 2.5i, 6.72 ( d , iH, J-= 9.1), 4.30 (dd, 1H, ABx, /= 11.0, 1.5), 4.19-4.06 (m, 1H), 4.06- 4.01 un. Hi). 3.82-3.73 (m, LH), 3.53-3.47 (m, IH), 1.71-1.61 (m, 2H), 1.38-1.29 (m, IH), O.1)1,' id, 3H. . --- 0.5). 0.96 (d, 3H. J:= 6.5). (2 ALL "^ ^.niino-3.4-jihvdro-3-isobutv]-4-(2.2.2-tnfluoroethy])-2//-1.4--benzoxazme (Slmicture_l6 oJ Scheme III, where R:'. R4. R5. R7. R8 = H. R° = isobutvl. R13 = CHZCF3): Tins compound was prepared by treatment of (3^?)-3,4-dihydro-3-isobutyl-7-nitro-4- (2,2,2-triflui)roeihyl)-lff-l,4-benzoxazine (0.22 g, 0.69 mmol) and 10% Pd/C (0.075 g) in 5 mL ethyl acetate under an Fi2 atmosphere for 16 h. The mixture was filtered througli Ci-'lite and concentrated to an oil. Flash chromatography (3:1 hexanes:ethyl acetate) afforded u. 13 g (65%) of (37?)-7-amino-3,4-dihydro-3-isobutyl-4-trifluoroethyl-2/f-l,4- benzoxazine. Data for (3J?)-7-amino-3,4-dihydro-3-isobutyl-4-trifluoroethyl-2//-l,4— berizoxazine: Rf 0.3 (3:1 hexanes:EtOAc); ^H NMR (400 MHz, CDC13) 6 6.63 (d, IH, / 3.5\6.r!oid. 1H,7=8.5, 2.6), 6.23 (d, IH, J= 2.5), 4.10 (dd, IH, ABx, J= 10.6, l.S), 3.'J" (del, IH, ABx, .7= 10.6, 2.3). 3.70-3.51 (m. 2H), 3.38 (broad s, 2H), 3.19-3.13 (m, IH). 1.75-1.63 irn. IH), 1.47-1.25 (m, 2H), 0.93 (d, 3H, J= 6.6), 0.89 (d, 3H, J= 6.6). -LiE): ^.3-4."-Tetrahvdro-3-isobutvl-4-(2.2.2-trifluoroethvl)-10-(tnfluoromethvlV S/-/-! l,41pxazino'2.3:,/1quinolin-8-one (Compound 155. Structure 17 of Scheme III, where R1. R3. R4. R5. R7. Rs = H. R2 = tnfluoromethvl R6 = isobutyl. R13 = CHgCFg), and 1.2.3,6-tetrahvdro-2-isobutvl-l-(2.2.2-tnfluoroethvl)-9-(trifluorbmethvl)-7gn. 41gxazmo[3.2-elqmnolm-7-one (Structure 18 of Scheme III, where R1. R3, R4. R5. R7 = H. R'_- tnfluoromethvl. R° - isobutyl. Rl j = CHgCFQ: This compound was prepared by treatment of (37?)-7-amino-3,4-dihydro-3-isobutyl-4-trifluoroethyl-277-l,4—benzoxazine (0.13 g, 0.45 mmol) and ethyl-4,4,4-trifluoroacetoacetate (0.25 g, 1.4 mmol) in 6 rriL toluene heated at reflux for 3h, followed by removal of solvent and treatment with 3 mL concentrated H2SO4 heated to 95 °C for 1 h. The mixture was poured into water (100 mL), neutralized with 6N NaOH, and extracted with chloroform (3 x 50 mL). The combined organic layers were washed with brine, dried over MgSCU, filtered, and concentrated. The baseline impurities and were removed and partial purification achieved by flash chromatography (95:5 CH2Cl2:MeOH). Further purification by HPLC (Kromasil, 0.5" semi-prep column, 70% MeOH/water at 3 mL/min) afforded 5.0 mg (3%) of Compound 1.55. and recrystalhzation of the other impure fractions (ethyl acetate:hexanes) afforded 17 rng (9%) of (2/0-1,2,3,6-tetrahydro-2-isobutyl-1 -(2,2?2-trifluoroethyl)-9-(trifluoromethyl)- 7/-/-•[ 1.4]oxazino| 3.2-o-]qumolm-7-one, the regioisomer of Compound 155. Data for Compound 155: 'H NMR (500 MHz, CDC13) 5 12.0-12.4 (v broad s, IH), 7.15 (s, 1H), 7 . 1 3 (d,./ - 9.0. IH), 7.01 (d. J= 9.0, 1H), 4.34 (d. J= 11, 1H), 3.99 (broad d, J = 10, 1H), 3.75-3.S3 ira. IH), 3.65-3.75 (in, IH), 3.35-3.40 (m, IH), 1.70-1.SO (m. IH), 1.40-1.50 (m, IH), 1.30-1.40 (m, IH), 0.95 (d, J- 6.5, 3H), 0.93 (d,/= 7.0, 3H). BIOLOGICAL EXAMPLES A. Steroid Receptor Activity Utilizing the "cis-trans" or "co-transfection" assay described by Evans et al., ^Science, .240:889-95 (May 13, 1988), the disclosure of which is incorporated by reference herein, the compounds of the present invention were tested and found to have strong, specific activity as agonists, partial agonists and antagonists of AR. This assay is described in further detail in U.S. Patent Nos. 4,981,784 and 5,071,773, the disclosures of which are incorporated herein by reference. The co-transfection assay provides a method for identifying functional agonists and partial agonists that mimic, or antagonists that inhibit, the effect of native hormones and quantifying their activity for responsive IR proteins. In this regard, the co-transfection assay mimics an in vivo system in-the laboratory. Importantly, activity in the cotransfection assay correlates very well with known in vivo activity, such that the cotransfection assay functions as a qualitative and quantitative predictor of a tested compounds :n \-ivo phamiacology. See, e.g., 1. Bergeret al. 41 J. SteroidBiochem. Molec. Biol, 7";3 (1992), the disclosure of which is herein incorporated by reference. In the co-transfection assay, a cloned cDNA for an IR (e.g., human PR, AR or GR) under the control of a constitutive promoter (e.g., the SV 40 promoter) is introduced by transfection (a procedure to induce cells to take up foreign genes) into a background cell substantially devoid of endogenous IRs. This introduced gene directs the recipient cells to make the IR protein of interest. A second gene is also introduced (co-transfected) into the same cells in conjunction with the ER. gene. This second gene, comprising the cDNA for a reporter protein, such as firefly luciferase (LUC), controlled by an appropriate hormone responsive promoter containing a hormone response element (HRE). This reporter plasnud functions as a reporter for the transcription-modulating activity of the target IR. Thus, the reporter acts as a surrogate for the products (mRNA then protein) normally expressed by a gene under control of the target receptor and its native hormone. flic eo-iransfection assay can detect small molecule agonists or antagonists of target IR;;. txposing the transfected cells to an agonist ligand compound increases reporter acin iry in the transfected cells. This activity can be conveniently measured, e.g., bv increasing luciferase production, which reflects compound-dependent, IR-mediated increases in reporter transcription. A partial agonist's activity can be detected in a manner similar to that of the full agonist, except that the maximum measured activity, e.g., luciferase production, is less than that of an agonist standard. For example, for AR, a partial agonist can be detected by measuring increased luciferase production, but the maximum effect at high concentration is Jess than the maximum effect for dihydrotestosterone. To detect antagonists, the co-transfection assay is carried out in the presence of a constant concentration of an agonist to the target IR (e.g., progesterone for PR) known u antagonist wfll decrease the reporter signal (e.g., luciferase production). The cotransfection assay is therefore useful to detect both agonists and antagonists of specific IRs. Furthermore, it determines not only whether a compound interacts with a particular Ill, but whether this interaction mimics (agonizes) or blocks (antagonizes) the effects of the native regulatory molecules on target gene expression, as well as the specificity and strength of this interaction. The activity of selected steroid receptor modulator compounds of the present invention weie evaluated utilizing the co-transfection assay and in standard IR binding assays, according to the following illustrative Examples. B. Co-transfection assav CV'-l cells (African green monkey kidney fibroblasts) were cultured in the presence of Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% charcoal resin-stripped fetal bovine serum (CH-FBS) then transferred to 96-well microtiter pjates one dav prior to transfection. To determine AR agonist and antagonist activity of the compounds of the present invention, tht C V-1 cells were transiently transfected by calcium phosphate coprecipuation according to the procedure of Berger et al., 41 J. Steroid Biochem. Mol. Bio!., 73? ( 1 °2 i with the following plasmids: pRShAR (5 ng/well), MTV-LUC reporter (1 00 ng'well}. pRS-B--Gal (50 ng/well) and filler DNA (pGEM; 45 ng/well). The receptor plusmid, pRShA.R, contains the human AR under constitutive control- of the SV-40 promoter, as more fully described in J.A. Simental et al., "Transciiptional activation and nuclear targeting signals of the human androgen receptor", 266 J. Biol. Cheni., 510 (1991). The reporter plasmid, MTV-LUC, contains the cDNA for firefly luciferase (LUC) under control of the mouse mammary tumor virus (MTV) long terminal repeat, a conditional promoter containing an androgen response element. See e.g., Berger et al. supra. In addition, pRS-B-Gal, coding for constitutive expression of E. coli Bgalactosidase (B-Gal), was included as an internal control for evaluation of transfection efficiency and compound toxicity. Six hours after transfection, media was removed and the cells were washed with phosphate-buffered saline (PBS). Media containing reference compounds (i.e. progesterone as a PR agonist, mifepristone ((llp,17(3)-ll-[4-(dimethylamino)phenyl]-17- hydjrox\-l~-(! -nropynyl)estra-4.9-dien-3-one: RU486; Roussel Uclaf) as a PR antagonist; diliydrotestosterone (DHT; Sigma Chemical) as an AR agonist and 2-OH-flutamide (the active metabolite of 2-methyl-7V-[4-nitro-3-(trifluoromethyl)phenyl]-pronanamide; Schering-Plough) as an AR antagonist; estradiol (Sigma) as an ER agonist and ICI 164,384 (>f-butyl-3,17-dihydroxy-7Vr-methyl-(7-cc,17-p)-estra-l,3,5(10)-triene-7- undecanamide; ICI Americas) as an ER antagonist; dexamethasone (Sigma) as a GR agonist and RU486 as a GR antagonist; and aldosterone (Sigma) as a MR agonist and spironolactone ((7-a-[acetylthio]-17-a-hydroxy-3-oxopregn-4-ene-21-carboxylic acid ylactone (Sigma) as an MR antagonist; and/or the modulator compounds of the present invention in concentrations ranging from 10~^ to 10"^ M were added to the cells. Three to four replicates were used for each sample. Transfections and subsequent procedures were performed on a Biomek 1000 automated laboratory work station. After 40 hours, the cells were washed with PBS, lysed with a Triton X-100-based buffer and assayed for LUC and fi-Gal activities using a luminometer or spectrophotorneter, respectively. For each replicate, the normalized response (MR) was calculated as: LUC response/B-Gal rate where B-Gal rate = B-Gal/6-Gal incubation time. The mean and standard error of the mean (SEM) of the NR were calculated. Data were plotted as the response of the compound compared to the reference compounds over the range of the close-response curve. For agonist experiments, the effective concentration that produced 50% of the maximum response (ECso) was quantified. Agonist efficacy was a function (%) of LUC expression relative to the maximum LUC production by the reference agonist for PR, AR., ER, GR or MR. Antagonist activity was determined by testing the amount of LUC expression in the presence of a fixed amount of DHT as an AR agonist and progesterone as a PR agonist at the EC5Q concentration. The concentration of a test compound that inhibited 50% of LLJC expression induced by the reference agonist was quantified (ICfO). in addition, the efficacy of antagonists was determined as a function (%) of maximal inhibition. Table 1: Agonist, partial agonist, antagonist and binding activity of androgen receptor modulator compounds of present invention, and the reference agonist, compound, dihydrotestosterone (DHT), a known synthetic androgen, fluoxymesterone (Fluox) and reference antagonist compounds, 2- hydroxyflutaniide (Flut) and Casodex (Cas), on hAR in CV-1 cells. Efficacy (%) for AR agonist is detennmed by comparing activity (e.g., luciferase production) of putative agonist to that of dihydrotestosterone (DHT). Efficacy (°>) for AR antagonist is determined by the percentage amount by which the luciferase production is reduced (maximum concentration of antagonist) from the luciferase production of the standard (DHT). (Table Removed) Table 2: Overall agonist and antagonist potency of selected androgen receptor modulator compounds of present, invention and the reference agonist and antagonist compounds shown in Table 1 on PR, AR, ER, GR and MR. (Table Removed) The oresent invention includes any combination of the various species and subgeneric groupings falling within the generic disclosure. This invention therefore includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. While in accordance with the patent statutes, description of the various embodiments and processing conditions have been provided, the scope of the invention is not to be limited thereto or thereby. Modifications and alterations of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims, rather than by the specific examples which have been presented by way of example. We claim: 1. A tricyclic quinolinone or quinoline-2(1H)-thione of formula I: (Formula Removed) wherein: R1 is selected from the group of hydrogen, F, Cl, Br, I, NO2, OR9, NR10Rn, S(O)„R9, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, C3 -C8 cycloalkyl, aryl, arylalkyl, heteroaryl, C2-C8 alkynyl and C1-C8 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; R2 is selected from the group of hydrogen, F, CI, Br, I, CF3, CF2CI, CF2H, CFH2, CF2OR9, CH2OR9, OR9, S(O)nR9, NR10Rn, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, C3 - C8 cycloalkyl, aryl, arylalkyl, heteroaryl, C2-C8 alkynyl and C2-C8 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; R3 and R4 each independently is selected from the group of hydrogen, OR9, S(O)nR9, NR10Rn, C(Y)ORn, C(Y)NR10Rn, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, C3-C8 cycloalkyl, aryl, arylalkyl, heteroaryl, C2-C8 alkynyl and C2-C8 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; or R3 and R4 taken together form a three to eight membered saturated or unsaturated carbocyclic or heterocyclic ring; or R and R taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R and R taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R and R taken together form a three to eight membered saturated or unsaturated heterocyclic ring; R5 and R6 each independently is selected from the group of hydrogen, CF3, CF2CI, CF2H, CFH2, C1-C8 alkyl, C1- C8 haloalkyl, C1-C8 heteroalkyl, C3 -C8 cycloalkyl, aryl, arylalkyl, heteroaryl, C2-C8 alkynyl and C2-C8 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; or R5 and R6 taken together form a three to eight membered saturated or unsaturated carbocyclic ring; or R5 and R13 taken together form a three to eight membered saturated or unsaturated heterocyclic ring; or R and R taken together form a three to eight membered saturated or unsaturated heterocyclic ring; R7 is selected from the group of hydrogen, F, CI, Br, I, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, aryl, heteroaryl, OR9, S(O)„R9, NR10Ru, C(Y)ORn and C(Y)NR10Rn, wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optionally substituted; R8 is selected from the group of hydrogen, F, CI, Br, I, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, aryl, heteroaryl, OR9, S(O)nR9, NR10Ru, C(Y)ORn and C(Y)NR10Ru, wherein the alkyl, haloalkyl, heteroalkyl, aryl and heteroaryl groups may be optionally substituted; R9 is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, aryl, heteroaryl and arylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R10 is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, aryl, heteroaryl, arylalkyl, CO2R12, C(O)R12, SO2R12 and,S(O)R12, wherein the alkyl, haloalkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R11 and R12 each independently is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, aryl, heteroaryl and arylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, aryl, heteroaryl and arylalkyl groups may be optionally substituted; R13 is selected from the group of C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3 -C8 cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl groups may be optionally substituted; R16 is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, COR17, CO2R17 and CONR12R17, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R17 is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl and C1-C8 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R18 is selected from the group of hydrogen, F, Br, Cl, I, CN, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, OR16, NR16R17, SR16, CH2R16, COR17, CO2R17, CONR16R17, SOR and SO2R , wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R19 is selected from the group of hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 heteroalkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3 -C8 cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl groups may be optionally substituted; m is selected from the group of 0, 1 and 2; n is selected from the group of 0, 1 and 2; V is selected from the group of O and S; W is selected from the group of NH, N{R13}, N{C(Y)Rn} and N{SO2Rn}; X is O or S; Y is O or S; and Z is selected from the group of NH, N{RU}, N{C(Y)Rn}, N{SO2R12} and N{S(O)R12}; and pharmaceutically acceptable salts thereof; wherein, when a group is optionally substituted, the group is substituted with one or more substituents independently selected from among C1-C12 alkyl, C2-C18 alkenyl, C2-C12 alkynyl, C1-C12 heteroalkyl, C1-C12 haloalkyl, C2-C18 haloalkenyl, C2-C12 haloalkynyl, C3-C8 cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkoxy, aryloxy, haloalkoxy, amino, alkylamino, dialkylamino, alkylthio, arylthio, heteroarylthio, oxo, carboxyester, carboxamido, acyloxy, hydrogen, F, CI, Br, I, CN, NO2, NH2, N3, NHCH3, N(CH3)2, SH, SCH3, OH, OCH3, OCF3, CH3, CF3, C(O)CH3, CO2CH3, CO2H, C(O)NH2, OR9, SR9 and NR10Rn. 2. A tricyclic quinolinone or quinoline-2(l.ff)-thione as claimed in claim 1, wherein R1 is selected from the group of hydrogen, F, Cl, OR9, NR10R11, S(O)nR9, C1- C4 alkyl, C1- C4 haloalkyl and C1-C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 3. A tricyclic quinolinone or quinoline-2(1H)-thione as claimed in claim 2, wherein R1 is selected from the group of hydrogen, F, Cl, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 4. A tricyclic quinolinone or quinoline-2(1H)-thione as claimed in claim 3, wherein R1 is selected from the group of hydrogen, F and optionally substituted C1- C4 alkyl. 5. A tricyclic quinolinone or quinoline-2(1H)-thione as claimed in claim 1, wherein R2 is selected from the group of hydrogen, F, Cl, Br, I, CF3, CF2C1, CF2H, CFH2, CF2OR9, CH2OR9, OR9, S(O)nR9, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, C2- C6 alkynyl and C2- C6 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, alkynyl and alkenyl groups may be optionally substituted. 6. A tricyclic quinolinone or quinoline-2(li/)-thione as claimed in claim 5, wherein R2 is selected from the group of hydrogen, F, CI, CF3, CF2C1, CF2H, CFH2, C1- C4 alkyl, C1-C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 7. A compound as claimed in claim 6, wherein R2 is selected from the group of hydrogen, C1- C2 alkyl, C1- C2 haloalkyl and C1- C2 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 8. A compound as claimed in 7, wherein R is CF3. 9. A compound as claimed in claim 1, wherein: R3 is selected from the group of hydrogen, C1- C6 alkyl, C1- C6 haloalkyl,, C1-C6 heteroalkyl, C(Y)ORn and C(Y)NR10R11, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; or R3and R6 taken together form a three to eight membered saturated or unsaturated carbocyclic ring. 10. A compound as claimed in 9, wherein R and R taken together form a four to six membered saturated or unsaturated carbocyclic ring. 11. A compound as claimed in claim 9, wherein R3 is selected from the group of hydrogen, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 12. A compound as claimed in claim 1, wherein R6 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, aryl, arylalkyl, heteroaryl, C2- C6 alkynyl and C2- C6 alkenyl, wherein the alkyl, heteroalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted. 13. A compound as claimed in claim 12, wherein R6 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, d - C4 alkyl, C1- C4 haloalkyl, C1- C4 heteroalkyl, C2-C4 alkynyl and C2- C4 alkenyl, wherein the alkyl, heteroalkyl, haloalkyl, alkynyl and alkenyl groups may be optionally substituted. 14. A compound as claimed in claim 13, wherein R6 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 15. A compound as claimed in claim 12, wherein R6 is selected from the group of aryl, arylalkyl and heteroaryl, wherein the aryl, arylalkyl and heteroaryl groups may be optionally substituted. 16. A compound as claimed in claim 1, wherein R5 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, C2-C6 alkynyl, C2- C6 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, alkynyl and alkenyl groups may be optionally substituted. 17. A compound as claimed in claim 16, wherein R5 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C6 alkyl, C1- C6 haloalkyl and C1- C6 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 18. A compound as claimed in claim 17, wherein R5 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 19. A compound as claimed in claim 18, wherein R5 is hydrogen or CF3. 20. A compound as claimed in claim 1, wherein R is selected from the group of hydrogen, F, Cl, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl, groups may be optionally substituted. 21. A compound as claimed in claim 1, wherein R8 is selected from the group of hydrogen, F, Cl, C1- C4 alkyl, C1- C4 haloalkyl and C1-C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl, groups may be optionally substituted. 22. A compound as claimed in claim 21, wherein R7 and R8 are each hydrogen or optionally substituted C1- C2 alkyl. 23. A compound as claimed in claim 1, wherein R9 is selected from the group of hydrogen, C1- C6 alkyl, C1- C6 haloalkyl and d - C6 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 24. A compound as claimed in claim 23, wherein R9 is selected from the group of hydrogen and optionally substituted C1- C4 alkyl. 25. A compound as claimed in claim 1, wherein R10 is selected from the group of hydrogen, S(O)R12, SO2R12, C(O)R12, CO2R12, C1- C6 alkyl, C1- C6 haloalkyl and C1- C6 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 26. A compound as claimed in claim 25, wherein R10 is selected from the group of hydrogen, S(O)R12, SO2R12, C(O)R12 and CO2R12. 27. A compound as claimed in claim 1, wherein R4 is selected from the group of hydrogen, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 28. A compound as claimed in claim 27, wherein R4 is selected from the group of hydrogen and optionally substituted C1- C2 alkyl. 29. A compound as claimed in claim 1, wherein R is selected from the group of CF3, CF2C1, CF2H, CFH2, CH2CF3, CH2CF2C1, CH2CC12F, C1- C6 alkyl, C3 - C6 cycloalkyl, C1- C6 haloalkyl, C1-C6 heteroalkyl, C2- Ce alkenyl, C2- Ce alkynyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein the alkyl, cycloalkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl groups may be optionally substituted; or R6 and R13 taken together form a five to seven membered saturated or unsaturated heterocyclic ring. 30. A compound as claimed in claim 29, wherein R is selected from the group of CF3, CF2C1, CF2H, CFH2, CH2CF3, CH2CF2CI, CH2CCI2F, C1- C4 alkyl, C1- C4 haloalkyl, C1- C4 heteroalkyi, C2- C4 alkenyl and aryl, wherein the alkyl, haloalkyl, heteroalkyi, alkenyl and aryl groups may be optionally substituted; or R and R taken together form a five to six membered saturated or unsaturated heterocyclic ring. 31. A compound as claimed in claim 30, wherein R13 is selected from the group of CF3, CF2C1, CF2H, CFH2, CH2CF3, CH2CF2Cl, CH2CCl2F, methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropylmethyl, allyl; or R6 and R13 taken together form a five membered saturated or unsaturated heterocyclic ring. 32. A compound as claimed in claim 1, wherein R18 is selected from the group of hydrogen, F, Cl, OR16, SR16, NR16R17, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyi, wherein the alkyl, haloalkyl and heteroalkyi groups may be optionally substituted. 33. A compound as claimed in claim 32, wherein R18 is selected from the group of hydrogen, F, Cl, OR16, SR16 andNR16R17. 34. A compound as claimed in claim 33, wherein R18 is selected from the group of hydrogen, F, Cl and OR16. 35. A compound as claimed in claim 1, wherein R19 is selected from the group of hydrogen, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyi, wherein the alkyl, haloalkyl and heteroalkyi groups may be optionally substituted. 36. A compound as claimed in claim 35, wherein R19 is selected from the group of hydrogen and optionally substituted C1-C4 alkyl. 37. A compound as claimed in claim 1, wherein m is 0 or 1. 38. A compound as claimed in claim 37, wherein m is 1. 39. A compound as claimed in claim 1, wherein W is N{C(Y)R11} or N{SO2R11}. 40. A compound as claimed in claim 1, wherein W is NH or N{R13}. 41. A compound as claimed in claim 1, wherein X is O. 42. A compound as claimed in claim 1, wherein X is S. 43. A compound as claimed in claim 1, wherein Y is S. 44. A compound as claimed in claim 1, wherein Y is O. 45. A compound as claimed in claim 1, wherein Z is NH or N{R11}. 46. A compound as claimed in claim 1, wherein V is S. 47. A compound as claimed in claim 1, wherein V is O. 48. A compound as claimed in claim 1, wherein: R1 is selected from the group of hydrogen, F, Cl, OR9, S(O)„R9, NR10R11, C1- C4 alkyl, C1- C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R2 is selected from the group of hydrogen, F, Cl, Br, I, CF3, CF2C1, CF2H, CFH2, CF2OR9, CH2OR9, OR9, S(O)„R9, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, C2- C6 alkynyl and C2- C6 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, alkynyl and alkenyl groups may be optionally substituted; R is selected from the group of hydrogen, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, C(Y)OR11 and C(Y)NR10R11, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; or R3 and R6 taken together form a three to eight membered saturated or unsaturated carbocyclic ring; R5 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C6 alkyl, C1 - C6 haloalkyl, C1- C6 heteroalkyl, C2- C6 alkynyl and C2- C6 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, alkynyl and alkenyl groups may be optionally substituted; R6 is selected from the group of hydrogen, CF3, CF2C1, CF2H, CFH2, C1- C6 alkyl, C1-C6 haloalkyl, C1- C6 heteroalkyl, aryl, arylalkyl, heteroaryl, C2- C6 alkynyl and C2- C6 alkenyl, wherein the alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, heteroaryl, alkynyl and alkenyl groups may be optionally substituted; or R and R taken together form a five to seven membered saturated or unsaturated heterocyclic ring. 49. A compound as claimed in claim 48, wherein: R7 is selected from the group of hydrogen, F, Cl, C1- C4 alkyl, C1- C4 haloalkyl and C1 - C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R is selected from the group of hydrogen, F, CI, C1- C4 alkyl, C1- C4 haloalkyl and Ci - C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted; R13 is selected from the group of CF3, CF2C1, CF2H, CFH2, CH2CF3, CH2CF2C1, CH2CCl2F, C1- C6 alkyl, C1- C6 haloalkyl, C1- C6 heteroalkyl, C3 - C6 cycloalkyl, C2- C6 alkenyl, C2- C6 alkynyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl groups may be optionally substituted; or R6 and R13 taken together form a five to seven membered saturated or unsaturated heterocyclic ring; and R18 is selected from the group of hydrogen, F, CI, OR16, SR16, NR16R17, C1- C4 alkyl, Q - C4 haloalkyl and C1- C4 heteroalkyl, wherein the alkyl, haloalkyl and heteroalkyl groups may be optionally substituted. 50. A compound as claimed in claim 49, wherein: m is 0 or 1; W is selected from the group of NH, N{R13}, N{C(Y)R11} and N{SO2R11}; X is selected from the group of O, S, NH and N{R11}; Y is O or S; and Z is NH or N{R11}. 51. A compound as claimed in claim 1, wherein the compound is selected from among: (3R)-2,3,4,7-Tetrahydro-3-methyl-10-(trifluoromemyl)-8H-[l,4]oxazmo[2,3-f]-quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3,4-dimethyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-4-Ethyl-2,3,4,7-tetrahydro-3-memyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-2, 3,4,7-Tetrahydro-3-methyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3-methyl-4-propyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-4-Allyl-2,3,4,7-tetrahydro-3-methyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-3-Ethyll-2,3,4,7-etrahydro-10-(trifluoromethyl)-8H-[1,4]-oxazino-[2,3-f]quinolin-8-one; (3R)-3-Ethyl-2,3,4,7-tetrahydro-4-methyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-3, 4-Diethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]- quinolin-8-one; (3R)-3-Ethyl-2,3,4,7-tetrahydro-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (3R)-4-(2-Chloro-2,2-difluoroethyl)-3-ethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-F]quinolin-8-one; (3R)-4-(2,2-Difluoroethyl)-3-ethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f)quinolin-8-one; (3R)-3-Ethyl-2,3,4,7-tetrahydro-4-propyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-4-Allyl-3-ethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-3-Ethyl-2,3,4,7-tetrahydro-4-isobutyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R/S)-2,3,4J-Tetrahydro-3-propyl-10-(trifluoromethyl)-8H-1,4]oxazino[2,3-f]quinolin-8-one; (3R/S)-2,3,4,7-Tetrahydro-4-methyl-3-propyl-10-(trifluoromethyl)-8H-[l,4]oxazino-[2,3-f]quinolin-8-one; (3R/S)-4-Ethyl-2,3,4,7-tetrahydro-3-propyl-4-(2,2,2-trifluoroethyl)-l(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; (3R/S)-2,3,4,7-Tetrahydro-3-propyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3-isopropyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3-isopropyl-4-methyl-10-(trifluoromethyl)-8H-[l,4]oxazino-[2,3-f]quinolin-8-one; (3R)-4-Ethyl-2,3,4,7-tetrahydro-3-isopropyl-10-(trifluoromethyl)-8H-[l,4]oxazino-[2,3-f]quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3-isopropyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-(2-Chloro-2,2-difluoroethyl)-2,3,4,7-tetrahydro-3 -isopropyl-10-(trifluoro-methyl)-8H-[l,4]oxazino[2,3-f|quinolin-8-one; (3R)-4-(2,2-Difluoroethyl)-2,3,4,7-tetrahydro-3-isopropyl-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f|quinolin-8-one; (3R)-4-Allyl-2,3,4,7-tetrahydro-3-isopropyl-10-(trifluoromethyl)-8H-[l,4]oxazino-[2,3-f]quinolin-8-one; (3R)-23,4,7-Tetrahydro-3-phenyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3 -phenyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-Cyclopropylmethyl-2,3,4,7-tetrahydro-3-phenyl-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (3R)-3-Benzyl-2, 3,4,7-tetrahydro-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H- [1,4]oxazino[2,3-f|quinolin-8-one; 2,3,4,7-Tetrahydro-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; 2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (7aR, 10aS)-7,7a,8,9,10,10a-Hexahydro-1 -(trifluoromethyl)-7-(2,2,2trifluoroethyl)-4H-cyclopenta[5,6][l,4]oxazino[2,3-f]quinolin-3-one; (7aR, 10aS)-7-Ethyl-7,7a,8,9,10,10a-hexahydro-1 -(trifluoromethyl)-4H-cyclopenta-[5,6][l,4]oxazino[2,3-f]quinolin-8-one; (7aR, 10aS)-7,7a,8,9,10,10a-Hexahydro-3-isopropoxy-1 -(trifluoromethyl)-7-(2,2,2-trifluoroethyl)-4H-cyclopenta[5,6][l,4]oxazino[2,3-f]quinolin-8-one; (±)-(2S,3R)-2,3,4,7-Tetrahydro-2,3-dimethyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; (6aR)-6a,7,8,9-Tetrahydro-4-(trifluoromethyl)-lH,6H-pyrrolo[1', 2':4,5][l,4]oxazino-[2,3-f]quinolin-8-one; 2,3,4,7-Tetrahydro-2,2,4-trimethyl-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]-quinolin-8-one; (±)-2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10-bis(trifluoromethyl)-8H-[l ,4]-oxazino[2,3-f]quinolin-8-one; (-)-2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)10-bis(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (+)-2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10-bis(trifluoromethyl)-8H-[l ,4]-oxazino-[2,3-f]quinolin-8-one; (±)-2, 3,4,7-Tetrahydro-3-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]- oxazino[2,3-f]quinolin-8-one; (±)-2,3,4,7-Tetrahydro-4-methyl-3 -(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one; (±)-4-Ethyl-2,3,4,7-tetrahydro-3-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]-oxazino[2,3-f]quinolin-8-one; (±)-2,3,4,7-Tetrahydro-3,4-bis(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (-)-2,3,4,7-Tetrahydro-3,4-bis(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (+)-2,3,4,7-Tetrahydro-3,4-bis(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H- [1,4]-oxazino[2,3-f|quinolin-8-one; (±)-4-Cyclopropylmethyl-2,3,4,7-tetrahydro-3-(2,2,2-trifluoroethyl)-10-(trifluoro-methyl)-8H-[l,4]oxazino[2,3-f|quinolin-8-one; (3R)-4-Cyclopropylmethyl-3 -ethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H- [1,4]- oxazino[2,3-f]quinolin-8-one; (3R)-4-(2-Chloroethyl)-2,3,4,7-tetrahydro-3 -isopropyl-10-(trifluoromethyl)-8H-[ 1,4] -oxazino[2,3-f]quinolin-8-one; (±)-2,3,4,7-Tetrahydro-2-methyl-4-(2,2,2-trifluoroethyl)-10-(trifluoroethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (3R)-3 -Ethyl-4-(2-hydroxy-2-methylpropyl)-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H-[1,4]-oxazino-[2,3-f]quinolin-8-one; and (3R)-2,3,4,7-Tetrahydro-3-isobutyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one. 52. A compound as claimed in claim 1, wherein said compound is selected from among: (3R)-2,3,4,7-Tetrahydro-3-methyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[1,4]oxazino[2,3-f)quinolin-8-one; (3R)-3-Ethyl-2,3,4,7-tetrahydro-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[ 1,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-(2-Chloro-2,2-difluoroethyl)-3-ethyl-253,4,7-tetrahydro-10-trifluoromethyl)-8H-[1,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-(2,2-Difluoroethyl)-3 -ethyl-2,3,4,7-tetrahydro-10-(trifluoromethyl)-8H- [1,4] -oxazino[2,3-f]quinolin-8-one; (3R)-2,3,4,7-Tetrahydro-3-isopropyl-4-(2,2,2-trifluoroethyl)-10-(trifluoromethyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-(2-Chloro-2,2-difluoroethyl)-2,3,4,7-tetrahydro-3 -isopropyl-10-(trifluoro-methyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; (3R)-4-(2,2-Difluoroethyl)-2,3,4,7-tetrahydro-3 -isopropyl-10-(trifluoromethyl)-8H-[ 1,4]oxazino [2,3-f]quinolin-8-one; (7aR,10aS)-7-Ethyl-7,7a,8,9,10,10a-hexahydro-1-(trifluoromethyl)-4H-cyclopenta-[5,6] [1,4]oxazino[2,3-f] quinolin-8-one; (7aR, 10aS)-7,7a,8,9,10,10a-Hexahydro-1 -(trifluoromethyl)-7-(2,2,2-trifluoroethyl)-4H-cyclopenta[5,6][l,4]oxazmo[2,3-f]quinolin-3-one; (±)-(25,3R)-2,3,4,7-Tetrahydro-2,3-dimethyl-4-(2,2,2-trifluoroethyl)-10-(trifluoro-methyl)-8H-[l,4]oxazino[2,3-f]quinolin-8-one; ,(±)2,3,4,7-Tetrahydro-4-(2,2,2-Mfluoroethyl)-3,10-bis(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one; (-)-2,3, 4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10-bis(trifluoromethyl)-8H-[l,4]- oxazino[2,3-f]quinolin-8-one; and (+)-2,3,4,7-Tetrahydro-4-(2,2,2-trifluoroethyl)-3,10-bis(trifluoromethyl)-8H-[l,4]-oxazino[2,3-f]quinolin-8-one. 53. A compound as claimed in claim 1 as and when used as a pharmaceutical composition along with a pharmaceutically acceptable carrier of the kind such as described herein.

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01286-delnp-2003-abstract.pdf

01286-delnp-2003-claims.pdf

01286-delnp-2003-correspondence-others.pdf

01286-delnp-2003-description (complete)-21-07-2008.pdf

01286-delnp-2003-description (complete).pdf

01286-delnp-2003-form-1.pdf

01286-delnp-2003-form-18.pdf

01286-delnp-2003-form-2.pdf

01286-delnp-2003-form-3.pdf

01286-delnp-2003-form-5.pdf

01286-delnp-2003-gpa.pdf

01286-delnp-2003-pct-101.pdf

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01286-delnp-2003-pct-220.pdf

01286-delnp-2003-pct-304.pdf

01286-delnp-2003-pct-401.pdf

01286-delnp-2003-pct-409.pdf

01286-delnp-2003-pct-416.pdf

1286-DELNP-2003-Abstract-(17-09-2008).pdf

1286-DELNP-2003-Claims-(17-09-2008).pdf

1286-DELNP-2003-Claims-(21-07-2008).pdf

1286-delnp-2003-complete specification (granted).pdf

1286-delnp-2003-correspondence-others-(17-09-2008).pdf

1286-DELNP-2003-Correspondence-Others-(21-07-2008).pdf

1286-delnp-2003-description (complete)-21-07-2008.pdf

1286-delnp-2003-form-1-(17-09-2008).pdf

1286-delnp-2003-form-2-(17-09-2008).pdf

1286-DELNP-2003-Form-2-(21-07-2008).pdf

1286-delnp-2003-form-3-(17-09-2008).pdf

1286-DELNP-2003-Form-3-(21-07-2008).pdf

1286-DELNP-2003-Form-5-(21-07-2008).pdf

1286-DELNP-2003-GPA-(21-07-2008).pdf