Title of Invention

"REVERSE TURN- MIMETIC COMPOUND OF FORMULA I AND COMPOSITION COMPRISING THE SAME"

Abstract

A reverse turn mimetic having the following general formula: wherein R1, R2, R3, R4, R5, R6, and R7, are the same or different and independently selected from C1-12 alkyl, C6-12 aryl and C7-12 arylalkyl, either substituted or unsubstituted with one or more of the following chemical moieties: -OH, -OR, -COOH, -COOR, -CONH2, -NH2, -NHR, -NRR, -SH, -SR, -SO2R, -SO2H, -SOR and halogen (including F, CI, Br and I), wherein each occurrence of R is independently selected from straight chain or branched, cyclic or noncyclic, substituted or unsubstituted, saturated or unsaturated C1-12 alkyl, C6-12 aryl and C7-12 arylalkyl moieties; naphthalene, heterocyclic compounds such as thiophene, pyrrole, furan, imidazole, oxazole, thiazole, pyrazole, 3-pyrroline, pyrrolidine, pyridine, pyrimidine, purine, quinoline, isoquinoline and carbazole, heteroalkyl derivatives of the alkyl portion of the lower chain alkyl and aralkyl moieties, including (but not limited to) alkyl and aralkyl phosphonates and silanes.

Full Text

The present invention relates to reverse turn-mimetic compound of formula I and composition comprising the same. TECHNICAL FIELD The present invention relates generally to reverse-turn mimetic structures and to a chemical library relating thereto. The invention also relates to applications in the treatment of cancer diseases and pharmaceutical compositions comprising them BACKGROUND ART Random screening of molecules for possible activity as therapeutic agents has occurred for many years and resulted in a number of important drug discoveries. While advances in molecular biology and computational chemistry have led to increased interest in what has been termed "rational drug design", such techniques have not proven as fast or reliable as initially predicted. Thus, in recent years there has been a renewed interest and return to random drug screening. To this end, particular strides having been made in new technologies based on the development of combinatorial chemistry libraries, and the screening of such libraries in search for biologically active members. In general, combinatorial chemistry libraries are simply a collection of molecules. Such libraries vary by the chemical species within the library, as well as the methods employed to both generate the library members and identify which members interact with biological targets of interest. While this field is still young, methods for generating and screening libraries have already become quite diverse and sophisticated. For example, a recent review of various combinatorial chemical libraries has identified a number of such techniques (Dolle, J. Com. Chem., 2(3): 383-433, 2000), including the use of both tagged and untagged library members (Janda, Proc. Natl. Acad. Sci. USA 91:10779-10785, 1994). Initially, combinatorial chemistry libraries were generally limited to members of peptide or nucleotide origin. To this end, the techniques of Houghten et al. illustrate an example of what is termed a "dual-defined iterative" method to assemble soluble combinatorial peptide libraries via split synthesis techniques (Nature (London) 354:84-86, 1991; Biotechnigues 13:412-421, 1992; Bioorg. Med. Chem. Lett. 3:405-412, 1993). By this technique, soluble peptide libraries containing tens of millions of members have been obtained. Such libraries have been shown to be effective in the identification of opioid peptides, such as methionine- and leucine-enkephalin (Dooley and Houghten, Life Sci. 52, 1509-1517, 1993), and a N-acylated peptide library has been used to identify acetalins, which are potent opioid antagonists (Dooley et al., Proc. Natl. Acad. Sci. USA 90:10811- 10815, 1993. More recently, an all D-amino acid opioid peptide library has been constructed and screened for analgesic activity against the mu ("u ") opioid receptor (Dooley et al, Science 266:2019-2022, 1994). While combinatorial libraries containing members of peptide and nucleotide origin are of significant value, there is still a need in the art for libraries containing members of different origin. For example, traditional peptide libraries to a large extent merely vary the arnrno acid sequence to generate library members. While it is well recognized that the secondary structures of peptides are important to biological activity, such peptide libraries do not impart a constrained secondary structure to its library members. To this end, some researchers have cyclized peptides with disulfide bridges in an attempt to provide a more constrained secondary structure (Tumelty et al., J. Ghent. Soc. 1067-68, 1994; Eichler et al., Peptide Res. 7:300-306, 1994). However, such cyclized peptides are generally still quite flexible and are poorly bioavailable, and thus have met with only limited success. More recently, non-peptide compounds have been developed which more closely mimic the secondary structure of reverse-turns found in biologically active proteins or peptides. For example, U.S. Pat. No, 5,440,013 to Kahn and published PCT W094/03494, PCT W001/00210A1, and PCT WO01/16135A2 to Kahn these disclose conformationally constrained, non-peptidic compounds, which mimic the three-dimensional structure of reverse-turns. While significant advances have been made in the synthesis and identification of conformationally constrained, reverse-turn mimetics, there remains a need .hi the art for small molecules, which mimic the secondary structure of peptides. There has been also a need in the art for libraries containing such members, as well as techniques for synthesizing and screening the library members against targets of interest, particularly biological targets, to identify bioactive library members. For example U.S. Pat. No. 5,929,237 and its continuation-in-part U.S. Pat. No. 6,013,458 to Kahn also discloses conformationally constrained compounds which mimic the secondary structure of reverse-rum regions of biologically active peptides and proteins. The synthesis and identification of conformationally constrained, reverse-turn mimetics and their application to diseases were well reviewed by Obrecht (Advances in Med. Chem., 4, 1-68, 1999). The present invention also fulfills these needs, and provides further related advantages by providing confomationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins. Wnt signaling pathway regulates a variety of processes including cell growth, ontogenesis, and development (Moon et al., 1997, Trends Genet. 13, 157-162 : Miller et al., 1999, Oncogene 18, 7860-7872 : Nusse and Varmus, 1992, Cell 69, 1073-1087 : Cadigan and Nusse, 1997, Genes Dev. 11, 3286-3305 : Peifer and Polakis, 2000 Science 287, 1606-1609 : Polakis 2000, Genes Dev. 14, 1837-1851). Wnt signaling pathway has been intensely studied in a variety of organisms. The activation of TCF4/p-catenin mediated transcription by Wnt signal transduction has been found to play a key role in its biological functions (Molenaar et al., 1996, Cell 86, 391-399 : Gat et al., 1998 Cell 95, 605-614 : Orford et al., 1999 J. Cell. Biol. 146, 855-868). In the absence of Wnt signals, tumor suppressor gene adenomatous polyposis coli (APC) simultaneously interacts with the serine kinase glycogen synthase kinase (GSK)-3p and p-catenin (Su et al, 1993, Science 262, 1734-1737: Yost et al., 1996 Genes Dev. 10, 1443-1454: Hayashi et al., 1997, Proc. Natl. Acad. Sci. USA, 94, 242-247: Sakanaka et al., 1998, Proc. Natl. Acad. Sci, USA, 95, 3020-3023: Sakanaka and William, 1999, J. Biol. Chem 274, 14090-14093). Phosphorylation of APC by GSK-3P regulates the interaction of APC with p-catenin, which in turn may regulate the signaling function of P-catenin (B. Rubinfeld et al., Science 272, 1023, 1996). Wnt signaling stabilizes P-catenin allowing its translocation to the nucleus where it interacts with members of the lymphoid enhancer factor (LEFl)/T-cell factor (TCF4) family of transcription factors (Behrens et al., 1996 Nature 382, 638-642 : Hsu et al., 1998, Mol. Cell. Biol. 18, 4807-4818 : Roose et all., 1999 Science 285,1923-1926). Recently c-myc, a known oncogene, -was shown to be a target gene for p-catenin/TCF4-mediated transcription (He et al., 1998 Science 281 1509-1512: Kolligs et al., 1999 Mol. Cell. Biol. 19, 5696-5706). Many other important genes, including cyclin Dl, and metalloproteinase, which are also involved in oncogenesis, have been identified to be regulated by TCF4/bata-catenin transcriptional pathway (Crawford et al., 1999, Oncogene 18, 2883-2891: Shtutman et al., 1999, Proc. Natl. Acad. Sci. USA., 11, 5522-5527 : Tetsu and McCormick, 1999 Nature, 398, 422-426). Moreover, overexpression of several downstream mediators of Wnt signaling has been found to regulate apoptosis (Moris et al., 1996, Proc. Natl. Acad. Sci. USA, 93, 7950-7954 : He et al., 1999, Cell 99, 335-345 : Orford et al, 1999 J. Cell. Biol., 146, 855-868: Strovel and Sussman, 1999, Exp. Cell. Res., 253, 637-648). Overexpression of APC in human colorectal cancer cells induced apoptosis (Moris et al., 1996, Proc. Natl. Acad. Sci. USA.,93, 7950-7954), ectopic expression of P-catenin inhibited apoptosis associated with loss of attachment to extracellular matrix (Orford et al, 1999, J. Cell Biol. 146, 855-868). Inhibition of TCF4/p-catenin transcription by expression of dominant-negative mutant of TCF4 blocked Wnt-1-mediated cell survival and rendered cells sensitive to apoptotic stimuli such as anti-cancer agent (Shaoqiong Chen et al., 2001, J. Cell. Biol., 152, 1, 87-96) and APC mutation inhibits apoptosis by allowing constitutive survivin expression, a well-known anti-apoptotic protein (Tao Zhang et al., 2001, Cancer Research, 62, 8664-8667). Although mutations in the Wnt gene have not been found in human cancer, a mutation in APC or (i-catenin, as is the case in the majority of colorectal tumors, results in inappropriate activation of TCF4, overexpression of c-myc and production of neoplastic growth (Bubinfeld et al, 1997, Science, 275, 1790-1792 : Morin et al, 1997, Science, 275, 1787-1790 : Casa et al, 1999, Cell. Growth. Differ. 10, 369-376). The tumor suppressor gene (APC) is lost or inactivated in 85% of colorectal cancers and in a variety of other cancers as well (Kinder and Vogelstein, 1996, Cell 87, 159-170). APC's principal role is that of a negative regulator of the Wnt signal transduction cascade. A center feature of this pathway involves the modulation of the stability and localization of a cytosolic pool of P-catenin by interaction with a large Axin-based complex that includes APC. This interaction results in phosphorylation of p-catenin thereby targeting it for degradation. CREB binding proteins (CBP)/p300 were identified initially in protein interaction assays, first through its association with the transcription factor CREB (Chrivia et al, 1993, Nature, 365, 855-859) and later through its interaction with the adenoviral-transforming protein E1A (Stein et al., 1990, J. Viol., 64, 4421-4427 : Eckner et al., 1994, Genes. Dev., 8, 869-884). CBP had a potential to participate in variety of cellular functions including transcriptional coactivator function (Shikama et al., 1997, Trends. Cell. Biol, 7, 230-236 : Janknecht and Hunter, 1996, Nature, 383, 22-23). CBP/p300 potentiates p-catenin-mediated activation of the siamois promoter, a known Wnt target (Hecht et al, 2000, EMBO L 19, 8, 1839-1850). p-catenin interacts directly with the CREB-binding domain of CBP and P-catenin synergizes with CBP to stimulate the transcriptional activation of TCF4/p-catenin (Ken-Ichi Takemaru and Randall T. Moon, 2000 J. Cell. Biol., 149, 2, 249-254). From this background, TCF4/p-catenin and CBP complex of Wnt pathway can be taken as target molecules for the regulation of cell growth, oncogenesis and apoptosis of cells, etc. That is, there is a need for compounds that block TCF4/p-catenin transcriptional pathway by inhibiting CBP, and therefore can be used for treatment of cancer, especially colorectal cancer. BRIFF DESCRIPTION OF THE DRAWING Fig 1. Shows a graph for the measurement of IC50 of a compound of the present invention for SW480 cells, wherein Cell growth inhibition on SW480 cells is measured at various concentrations of the compound prepared in Example 4 in order to obtain the IC50 value. Specifically, the degree of inhibition in firefly and renilla luciferase activities by said test compound was determined. As a result, IC50 of said test compound against SW480 cell growth was found as disclosed in Table 4. Detailed procedures are the same as disclosed in Example 6. DISCLOSURE OF THE INVENTION The present invention is directed to conformationally constrained compounds which mimic the secondary structure of reverse-turn regions of biological peptide and proteins (also referred to herein as "reverse-turn mimetics" and chemical libraries relating thereto. This invention also discloses libraries containing such compounds, as well as the synthesis and screening thereof. The reverse-turn mimetic structures of the present invention are useful as bioactive agents, including (but not limited to) use as. diagnostic, prophylactic and/or therapeutic agents. The reverse-turn mimetic structure libraries of this invention are useful in the identification of such bioactive agents. In the practice of the present invention, the libraries may contain from tens to hundreds to thousands (or greater) of individual reverse-turn structures (also referred to herein as "members"). The compounds of the present invention have the following general formula (I): (Figure Remove) wherein A is -(CHR3)- or -(C=0)-, B is -(CHR^- or -(C=0)-, D is -(CHR,)- or -(CO)-, E is -(ZR«)- or -(00)-, G is -(XR,).-, -(CHR7)-(NR8)-J -(OO)-(Xig-, or -(OO)-, W is -Y(C=O)-, -(C=O)NH-, -(SO2)- or nothing, Y is oxygen or sulfur, X and Z is independently nitrogen or CH, n=0 or 1; and R,, R2, R3, R4, Rj, R6, R7, R8 and R, are the same or different and independently selected from an amino acid side chain moiety or derivative thereof, the remainder of the molecule, a linker and a solid support, and stereoisomers thereof. In the embodiment wherein A is -(CHR3)-, B is -(C=O)-, D is -(CHR5)-, E is -(C=O)-, and G is -(XR7X-, the compounds of this invention have the following formula (II): (Figure Remove) Wherein W, Y and n are as defined above, and R,, R2, R3, R5 and R7 are as defined in the following detailed description. In the embodiment wherein A is -(CO)-, B is -(CHRJ -, D is -(C=0)-, E is -(ZRJ-, and G is -(C=0)-(XR9)-t the compounds of this invention have the following fonnula (III): (Figure Remove) wherein W, Y and n are as defined above, Z is nitrogen or CH (when Z is CH, then X is nitrogen), and R,, R2, R4, Rj and R, are as defined in the following detailed description. In the embodiment wherein A is -(C=O)-, B is -(CHR,)-, D is -(C=O)-, E is -(ZRj)-, and G is (XR7)n-, the compounds of this invention have the following general formula (IV): (Figure Remove) wherein W, Y and n are as defined above, Z is nitrogen or CH (when Z is nitrogen, then n is zero, and when Z is CH, then X is nitrogen and n is not zero), and R,5 Rj, R4, R6 and R7, are as defined in the following detailed description. The present invention is also directed to libraries containing compounds of formula (I) above, as well as methods for synthesizing such libraries and methods for screening the same to identify biologically active compounds. Compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier or diluent are also disclosed. Especially, the present invention relates pharmaceutical compositions containing thereof for treating disorders including cancers which are associated with Wnt signaling pathway. It further relates to methods for treating disorders including cancer which are associated with Wnt signaling pathway. These and other aspects of this invention will be apparent upon reference to the attached figures and following detailed description. To this end, various references are set forth herein, which describe in more detail certain procedures, compounds and/or compositions, and are incorporated by reference in their entirety. In below, the present invention is illustrated in detail. In one aspect of the present invention, a reverse-rum mimetic structure is disclosed having the following formula (I): wherein A is -(CHR3)- or -(CO)-, B is -(CHRJ- or -(C=O)-, D is -(CHR5)- or -(C=O)-, E is -(ZRs)- or -(00)-, G is - More specifically, R,, R2, R3, R,, Rj, R^, R7, Rg and R*, are independently selected from the group consisting of arninoC2.5alkyl, guanidineC2.5alkyl, CMalkylguanidinoC2. 5alkyl, diCMalkylguanidino-C2.Jalkyl, amidinoC2.5alkyl,CMalkylamidinoC2.5alkyl, diC,_ 4alkylamidinoC2.5alkyl, C,.3alkoxy, Phenyl, substituted phenyl (where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, C1.4dialkylamino, halogen, perfluoro CMalkyl, C,.4alkyl, C,. 3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), benzyl, substituted benzyl (where the substituents on the benzyl are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, CMdialkylarnino, halogen, perfluoro C14alkyl, C,.3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), naphthyl, substituted naphthyl (where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, C,.4alkylamino, C,.4diaUcylamino, halogen, perfluoro CMalkyl, CMalkyl, C,.3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), bis-phenyl methyl, substituted bis-phenyl methyl (where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, C,. 4alkylamino, CMdialkylamino, halogen, perfluoro CMalkyl, C,.4alkyl, C,.3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), pyridyl, substituted pyridyl, (where the substituents are independently selected from one or more of amino amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, CMdialkylamino, halogen, perfluoro CMalkyl, CMalkyl, C,. 3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl ), pyridylC^alkyl, substituted pyridylCMalkyl (where the pyridine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, C,. 4dialkylamino, halogen, perfluoro CMalkyl, CMalkyl, C,.3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), pyrimidylCMalkyl, substituted pyrimidylCMalkyl (where the pyrimidine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, CMdialkylamino, halogen, perfluoro CMalkyl, CMalkyl3 C^alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), triazin-2-yl-C,. 4alkyl, substituted rriazm-2-yl-CMalkyl (where the triazine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, Q. 4alkylamino, CMdialkylamino, halogen, perfluoro CMalkyl, CMalkyl, C^alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), imidazoC^alkyl, substituted imidazol CMalkl (where the imidazole sustituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, amidrazonyl, CMalkylamino, CMdialkylamino, halogen, perfluoro CMalkyl, CMalkyl, C,.3alkoxy, nitro, carboxy, cyano, sulfuryl of hydroxyl), imidazolinylCMalkyl, N-amidinopiperazinyl-N-CMalkyl, hydroxyC2.5alkyl, C,. salkylaminoCj^alkyl, hydroxyCj.jalkyl, CLjalkylaminoCa.jalkyl, C,.5dialkylaminoCj.jalkyl, N-amidinopiperidinylCMalkyl and 4-aminocyclohexylC0_2alkyl. In one embodiment, R,, R^ Rg of E, and R7, Rg and R,, of G are the same or different and represent the remainder of the compound, and R3 of A, R^ of B or Rj of D is selected from an amino acid side chain moiety or derivative thereof. As used herein, the term "remainder of the compound" means any moiety, agent, compound, support, molecule, linker, amino acid, peptide or protein covalently attached to the reverse-turn mimetic structure at R,, R^, Rj, Rj, R7, R, and/or R, positions. This term also includes amino acid side chain moieties and derivatives thereof. As used herein, the term "amino acid side chain moiety" represents any amino acid side chain moiety present in naturally occurring proteins including (but not limited to) the naturally occurring amino acid side chain moieties identified in Table 1. Other naturally occurring amino acid side chain moieties of this invention include (but are not limited to) the side chain moieties of 3,5-dibromotyrosine, 3,5-diiodotyrosine, hydroxylysine, y-carboxyglutamate, phosphotyrosine and phosphoserine. In addition, glycosylated amino acid side chains may also be used in the practice of this invention, including (but not limited to) glycosylated threonine, serine and asparagine. (Table Remove) TABLE 1 Amino Acid Side Chain Moieties Amino Acid Side Chain Moiety Amino Acid -H Glycine -CHj Alanine -CH(CH3)2 Valine -CH2 CH(CH3)2 -CH(CH3)CH2 CH3 -(CH2)3NHC(NH2)NH2+ CH, Leucine Isoleucine Lysine Arginine -CHjCOCT -CH2CH2COQ--CH2CONH2 -CH2CH2CONH2 Histidine Aspartic acid Glutamic acid Asparagine Glutamine Phenylalanine lyrosine -CH2SH -CHjCHjSCH-, -CH2OH -CH(OH)CH3 Tryptophan Cysteine Methionine Serine Threonine Proline OH Hydroxyproline In addition to naturally occurring amino acid side chain moieties, the amino acid side chain moieties of the present invention also include various derivatives thereof. As used herein, a "derivative" of an amino acid side chain moiety includes modifications and/or variations to naturally occurring amino acid side chain moieties. For example, the amino acid side chain moieties of alanine, valine, leucine, isoleucine and phenylalanine may generally be classified as lower chain alkyl, aryl, or arylalkyl moieties. Derivatives of amino acid side chain moieties include other straight chain or branched, cyclic or noncyclic, substituted or unsubstituted, saturated or unsaturated lower chain alkyl, aryl or arylalkyl moieties. As used herein, "lower chain alkyl moieties" contain from 1-12 carbon atoms, "lower chain aryl moieties" contain from 6-12 carbon atoms and "lower chain aralkyl moieties" contain from 7-12 carbon atoms. Thus, in one embodiment, the ammo acid side chain derivative is selected from a C,_12 alkyl, a C6.12 aryl and a C7.12 arylalkyl, and in a more preferred embodiment, from a C,,7 alkyl, a CMO aryl and a C7.n arylalkyl. Amino side chain derivatives of this invention further include substituted derivatives of lower chain alkyl, aryl, and arylalkyl moieties, wherein the substituent is selected from (but are not limited to) one or more of the following chemical moieties: -OH, -OR, -COOH, -COOR, -CONH2> -NH,, -NHR, -NRR, -SH, -SR, -SO2R, -SO2H, -SOR and halogen (including F, Cl, Br and I), wherein each occurrence of R is independently selected from straight chain or branched, cyclic or noncyclic, substituted or unsubstituted, saturated or unsaturated lower chain alkyl, aryl and aralkyl moieties. Moreover, cyclic lower chain alkyl, aryl and arylalkyl moieties of this invention include naphthalene, as well as heterocyclic compounds such as thiophene, pyrrole, furan, imidazole, oxazole, thiazole, pyrazole, 3-pyrroline, pyrrolidine, pyridine, pyrimidine, purine, quinoline, isoquinoline and carbazole. Amino acid side chain derivatives further include heteroalkyl derivatives of the alkyl portion of the lower chain alkyl and aralkyl moieties, including (but not limited to) alkyl and aralkyl phosphonates and silanes. Representative R,, R^, Rj, RS, R7, Rg and R, moieties specifically include (but are not limited to) -OH, -OR, -COR, -COOR, -CONHj, -CONR, -CONRR, -NH2, -NHR, -NRR, -S02R and -COSR, wherein each occurrence of R is as defined above. In a further embodiment, and in addition to being an amino acid side chain moiety or derivative thereof (or the remainder of the compound in the case of R,, Rj, R5, R6, R7, R8 and Rj), R,, R2, R5, R6, R7, R8 or Rsinay be a linker facilitating the linkage of the compound to another moiety or compound. For example, the compounds of this invention may be linked to one or more known compounds, such as biotin, for use in diagnostic or screening assay. Furthermore, R,, R2, R5, R In the embodiment wherein A is -(CHR3)-, B is -(C=O)-, D is -(CHRs)-, E is - (C=O)-, G is -pCR7)n-, the reverse turn mimetic compound of this invention have the following formula (II): (Figure Remove) wherein R,, Rj, R3) Rj, R7, W, X and n are as defined above. In a preferred embodiment, R,, R2 and R7 represent the remainder of the compound, and R3 or Rj is selected from an amino acid side chain moiety. In the embodiment wherein A is -(C=O)-, B is -(CHR,) -, D is -(C=O)-, E is -(ZRg)-, G'is -(C=0)-(XR5i)-, the reverse turn mimetic compound of this invention have the following general formula (HI): (Figure Remove) wherein R,, Rj, R4, R^ R,, W and X are as defined above, Z is nitrogen or CH (when Z is CH, then X is nitrogen). In a preferred embodiment, R,, R^ , R^ and R,, represent the remainder of the compound, and R4 is selected from an amino acid side chain moiety. In a more specific embodiment wherein A is -(C=O)-, B is -(CHR,)-, D is -(C=O)-, E is -(ZRg)-, G is (XR,),,-., the reverse turn mimetic compound of this invention have the following formula (TV): (Figure Remove) wherein R,, R2) R4, Rg, R7, W, X and n are as defined above, and Z is nitrogen or CH (when Z is nitrogen, then n is zero, and when Z is CH, then X is nitrogen and n is not zero). In a preferred embodiment, Ru R^, R6 and R7 represent the remainder of the compound, and R The reverse-turn mimetic structures of the present invention may be prepared by utilizing appropriate starting component molecules (hereinafter referred to as "component pieces"). Briefly, in the synthesis of reverse-rum mimetic structures having formula (II), first and second component pieces are coupled to form a combined first-second intermediate, if necessary, third and/or fourth component pieces are coupled to form a combined third-fourth intermediate (or, if commercially available, a single third intermediate may be used), the combined first-second intermediate and third-fourth intermediate (or third intermediate) are then coupled to provide a first-second-third-fourth intermediate (or first-second-third intermediate) which is cyclized to yield the reverse-turn mimetic structures of this invention. Alternatively, the reverse-turn mimetic structures of formula (II) may be prepared by sequential coupling of the individual component pieces either step wise in solution or by solid phase synthesis as commonly practiced in solid phase peptide synthesis. Within the context of the present invention, a "first component piece" has the following formula SI: (Figure Remove) wherein R, as defined above, and R is a protective group suitable for use in peptide synthesis. Suitable R groups include alkyl groups and, in a preferred embodiment, R is a methyl group. Such first component pieces may be readily synthesized by reductive amination or substitution reaction by displacement of HjN-Rj from CH(OR)2-CHO or CH(OR)2-CH2-Hal (wherein Hal means a halogen atom). A "second component piece" of this invention has the following formula S2: H I' ,*L As P y^o (S2) R where L, is carboxyl-activation group such as halogen atom, R4 is as defined above, and P is an amino protective group suitable for use in peptide synthesis. Preferred protective groups include t-butyl dimethylsilyl (TBDMS), t-Butyloxycarbonyl (BOC), Methyloxycarbonyl (MOC), 9H-Fluorenylmethyloxycarbonyl (FMOC), and allyloxycarbonyl (Alloc). When L is -C(0)NHR, -NHR may be an carboxyl protective group. N-Protected amino acids are commercially available. For example, FMOC amino acids are available from a variety of sources. The conversion of these compounds to the second component pieces of this invention may be readily achieved by activation of the carboxylic acid group of the N-protected amino acid. Suitable activated carboxylic acid groups include acid halides where X is a halide such as chloride or bromide, acid anhydrides where X is an acyl group such as acetyl, reactive esters such as an N-hydroxysuccinimide esters and pentafluorophenyl esters, and other activated intermediates such as the active intermediate formed in a coupling reaction using a carbodiimide such as dicyclohexylcarbodiimide (DCC). In the case of the azido derivative of an amino acid serving as the second component piece, such compounds may be prepared from the corresponding amino acid by the reaction disclosed by Zaloom et al. (J. Org. Chem. 46:5173-76, 1981). Alternatively, the first piece of the invention may have the following formula SI1: (SI') RO wherein R is as defined above and L2 is a leaving group such as halogen atom or tosyl group, and the second piece of the invention may have the following formula S2': -R: HN JL J=s- Y y^ ^0 (S21) R4 wherein Rj,, R3 and P are as defined above, A "third component piece" of this invention has the following formula S3a or S3b: or (S3«) (S3b) where G, E, Lj and L2 are as defined above. Suitable third component pieces are commercially available from a variety of sources or can be prepared by any known method in organic chemistry. More specifically, the reverse-turn mimetic structures of this invention of formula (II) are synthesized by reacting a first component piece with a second component piece to yield a combined first-second intermediate, followed by either reacting the combined first-second intermediate with third component pieces sequentially to provide a combined first-second-third-fourth intermediate, and then cyclizing this intermediate to yield the reverse-turn mimetic structure. The general synthesis of a reverse-turn having structure I' may be synthesized by the following technique. A first component piece 1 is coupled with a second component piece 2 by using coupling reagent such as phosgene to yield, after N-deprotection, a combined first-second intermediate 1-2 as illustrated below: (Formula Remove) wherein, R, Rj, R4, R7, Fmoc, Moc and X are as defined above, and Pol represents a polymeric support. The syntheses of representative component pieces of this invention are described in Preparation Examples and working Examples. The reverse-turn mimetic structures of formula (HI) and (TV) may be made by techniques analogous to the modular component synthesis disclosed above, but with appropriate modifications to the component pieces. As mentioned above, the reverse-turn mimetics of USP 6,013,458 to Kahn, et al. are useful as bioactive agents, such as diagnostic, prophylactic, and therapeutic agents. The opiate receptor binding activity of representative reverse-turn mimetics is presented in Example 9 of said USP 6,013,458, wherein the reverse-turn mimetics of this invention were found to effectively inhibit the binding of a radiolabeled enkephalin derivative to the 5 and u opiate receptors, of which data demonstrates the utility of these reverse-turn mimetics as receptor agonists and as potential analgesic agents. The reverse-turn mimetic structures of the present invention will be useful as bioactive agents, such as diagnostic, prophylactic, and therapeutic agents. Therefore, since the compounds according to the present invention are of reverse-turn mimetic structures, it may be useful for modulating a cell signaling transcription factor related peptides in a warm-blooded animal, comprising administering to the animal an effective amount of the compound of formula (I). Further, the reverse-turn mimetic structures of the present invention may also be effective for inhibiting peptide binding to PTB domains in a warm-blooded animal; for modulating G protein coupled receptor (GPCR) and ion channel in a warm-blooded animal; for modulating cytokines in a warm-blooded animal. Meanwhile, it has been found that the compounds of the formula (I), especially compounds of formula (VI) are effective for inhibiting or treating disorders modulated by Wnt-signaling pathway, such as cancer, especially colorectal cancer. (Figure Remove) (VI) wherein, R, is a bicyclic aryl group having 8 to 11 ring members, which may have 1 to 3 heteroatoms selected from nitrogen, oxygen or sulfur, and Rb is a monocyclic aryl group having 5 to 7 ring members, which may have 1 to 2 heteroatoms selected from nitrogen, oxygen or sulfur, and aryl ring in the compound may have one or more substituents selected from a group consisting of halide,.hydroxy, cyano, lower alkyl, and lower alkoxy group. Therefore, it is an object of the present invention to provide a pharmaceutical composition comprising a safe and effective amount of the compound having general formula (VI) and pharmaceutically acceptable carrier, which can be used for treatment of disorders modulated by Wnt signaling pathway, especially by TCF4- p-catenin- CBP complex. Further, the present invention is to provide a method for inhibiting the growth of tumor cells by using the above-described composition of the present invention; a method for inducing apoptosis of tumor cells by using the above-described composition of the present invention; a method for treating a disorder modulated by TCF4-J3 catenin-CBP complex by using the above-described composition of the present invention; and a method of treating cancer such as colorectal cancer by administering the composition of the present invention together with other anti-cancer agent such as 5-fluorouracil (5-FU), taxol, cisplatin, mitomycin C, tegafur, raltitrexed, capecitabine, and irinotecan, etc. In a preferred embodiment of the present invention, the compound of the present invention has a (6S,10R)-configuration as follows: (Figure Remove) wherein R., and Rb have the same meanings as defined above. In another aspect of this invention, libraries containing reverse-turn mimetic structures of the present invention are disclosed. Once assembled, the libraries of the present invention may be screened to identify individual members having bioactivity. Such screening of the libraries for bioactive members may involve; for example, evaluating the binding activity of the members of the library or evaluating the effect the library members have on a functional assay. Screening is normally accomplished by contacting the library members (or a subset of library members) with a target of interest, such as, for example, an antibody, enzyme, receptor or cell line. Library members, which are capable of interacting with the target of interest, are referred to herein as "bioactive library members" or "bioactive mimetics". For example, a bioactive mimetic may be a library member which is capable of binding to an antibody or receptor, which is capable of inhibiting an enzyme, or which is capable of eliciting or antagonizing a functional response associated, for example, with a cell line. In other words, the screening of the libraries of the present invention determines which library members are capable of interacting with one or more biological targets of interest. Furthermore, when interaction does occur, the bioactive mimetic (or mimetics) may then be identified from the library members. The identification of a single (or limited number) of bioactive mimetic(s) from the library yields reverse-turn mimetic structures which are themselves biologically active, and thus useful as diagnostic, prophylactic or therapeutic agents, and may further be used to significantly advance identification of lead compounds in these fields. Synthesis of the peptide mimetics of the library of the present invention may be accomplished using known peptide synthesis techniques, in combination with the first, second and third component pieces of this invention. More specifically, any amino acid sequence may be added to the N-terminal and/or C-terminal of the conformationally constrained reverse-turn mimetic. To this end, the mimetics may be synthesized on a solid support (such as PAM resin) by known techniques (see, e.g., John M. Stewart and Jam's D. Young, Solid Phase Peptide Synthesis, 1984, Pierce Chemical Comp., Rockford, fll.) or on a silyl-linked resin by alcohol attachment (see Randolph et al., J, Am Chem. Soc. 117:5712-14,1995). In addition, a combination of both solution and solid phase synthesis techniques may be utilized to synthesize the peptide mimetics of this invention. For example, a solid support may be utilized to synthesize the linear peptide sequence up to the point that the conformationally constrained reverse-turn is added to the sequence. A suitable conformationally constrained reverse-turn mimetic structures which has been previously synthesized by solution synthesis techniques may then be added as the next "amino acid" to the solid phase synthesis (i.e., the conformationally constrained reverse-turn mimetic, which has both an N-terminus and a C-terminus, may be utilized as the next amino acid to be added to the linear peptide). Upon incorporation of the conformationally constrained reverse-turn mimetic structures into the sequence, additional amino acids may then be added to complete the peptide bound to the solid support. Alternatively, the linear N-terminus and C-terminus protected peptide sequences may be synthesized on a solid support, removed from the support, and then coupled to the conformationally constrained reverse-turn mimetic structures in solution using known solution coupling techniques. In another aspect of this invention, methods for constructing the libraries are disclosed. Traditional combinatorial chemistry techniques (see, e.g., Gallop et al., J. Med. Chem. 37:1233-1251, 1994) permit a vast number of compounds to be rapidly prepared by the sequential combination of reagents to a basic molecular scaffold. Combinatorial techniques have been used to construct peptide libraries derived from the naturally occurring amino acids. For example, by taking 20 mixtures of 20 suitably protected and different amino acids and coupling each with one of the 20 amino acids, a library of 400 (i.e., 202) dipeptides is created. Repeating the procedure seven -times results in the preparation of a peptide library comprised of about 26 billion (i.e., 208) octapeptides. Specifically, synthesis of the peptide mimetics of the library of the present invention may be accomplished using known peptide synthesis techniques, for example, the General Scheme of [4,4,0] Reverse-Turn Mimetic Library as follows: (Formula Remove) Synthesis of the peptide mimetics of the libraries of the present invention was accomplished using a FlexChem Reactor Block which has 96 well plates by known techniques. hi the above scheme 'Pol' represents a bromoacetal resin (Advanced ChemTech) and detailed procedure is illustrated below. Step 1 A bromoacetal resin (37mg, 0.98 mmol/g) and a solution of R2-amine in DMSO (1.4mL) were placed in a Robbins block (FlexChem) having 96 well plates. The reaction mixture was shaken at 60 °C using a rotating oven [Robbins Scientific] for 12 hours. The resin was washed with DMF, MeOH, and then DCM Step 2 A solution of commercial available FmocAmino Acids (4 equiv.), PyBob (4 equiv.), HOAt (4 equiv.), and DffiA (12 equiv.) in DMF was added to the resin. After the reaction mixture was shaken for 12 hours at room temperature, the resin was washed with DMF, MeOH, and then DCM. Step 3 To the resin swollen by DMF before reaction was added 25% piperidine in DMF and the reaction mixture was shaken for 30 min at room temperature. This deprotection step was repeated again and the resin was washed with DMF, Methanol, and then DCM. A solution of hydrazine acid (4 equiv.), HOBt (4 equiv.), and DIG (4 equiv.) in DMF was added to the resin and the reaction mixture was shaken for 12 hours at room temperature. The resin was washed with DMF, MeOH, and then DCM. Step 4a (Where hydrazine acid is MOC carbamate) The resin obtained in Step 3 was treated with formic acid (1.2 mL each well) for 18 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under a reduced pressure using SpeedVac [SAVANT] to give the product as oil. The product was diluted with 50% water/acetonitrile and then lyophilized after freezing. Step 4b (Where Fmoc hydrazine acid is used to make Urea through isocynate) To the resin swollen by DMF before reaction was added 25% piperidine in DMF and the reaction mixture was shaken for 30 min at room temperature. This deprotection step was repeated again and the resin was washed with DMF, Methanol, then DCM. To the resin swollen by DCM before reaction was added isocynate (5 equiv.) in DCM. After the reaction mixture was shaken for 12 hours at room temperature the resin was washed with DMF, MeOH, then DCM. The resin was treated with formic acid (1.2 mL each well) for 18 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under a reduced pressure using SpeedVac [SAVANT] to give the product as oil. The product was diluted with 50% water/acetonitrile and then lyophilized after freezing. Step 4c (Where Fmoc-hydrazine acid is used to make Urea through active carbamate) To the resin swollen by DMF before reaction was added 25% piperidine in DMF and the' reaction mixture was shaken for 30 min at room temperature. This deprotection step was repeated again and the resin was washed with DMF, MeOH, and then DCM. To the resin swollen by DCM before reaction was added p-nitrophenyl chloroformate (5 equiv.) and diisopropyl ethylamine (5 equiv.) in DCM. After the reaction mixture was shaken for 12 hours at room temperature, the resin was washed with DMF, MeOH, and then DCM. To the resin was added primary amines in DCM for 12 hours at room temperature and the resin was washed with DMF, MeOH, and then DCM. After reaction the resin was treated with formic acid (1.2 mL each well) for 18 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under a reduced pressure using SpeedVac [SAVANT] to give the product as oil. The product was diluted with 50% water/acetonitrile and then lyophilized after freezing. To generate these block libraries the key intermediate hydrazine acids were synthesized according to the procedure illustrated in Preparation Examples. Table 2 shows a [4,4,0] Reverse turn mimetics library which can be prepared according to the present invention, of which representative preparation is given in Example 4 [Table 2] The [4,4,0]Reverse turn mimetics library (Table Remove) In addition, synthesis of the peptide mimetics of the library of the present invention may be accomplished using the General Scheme of [4,3,0] Reverse-Turn Mimetic Library as follows: (Figure Remove) Synthesis of the peptide mimetics of the bicyclic template libraries of the present invention was accomplished using FlexChem Reactor Block which has 96 well plate by known techniques. In the above scheme 'Pol' represents Bromoacetal resin (Advanced ChemTech) and detailed procedure is illustrated bellow. Stepl The bromoacetal' resin (1.6mrnol/g) and a solution of Rl amine in DMSO (2M solution) were placed in 96 well Robbing block (FlexChem). The reaction mixture was shaken at 60 °C using rotating oven [Robbins Scientific] for 12 hours. The resin was washed with DMF, MeOH, and then DCM Step 2 A solution of commercial available Fmoc-Amino Acids (4 equiv.), PyBob (4 equiv.), HOAt (4 equiv.), and DIEA (12 equiv.) in DMF was added to the resin. After the reaction mixture was shaken for 12 hours at room temperature, the resin was washed with DMF, MeOH, and then DCM. Step 3 To the resin swollen by DMF before reaction was added 25% piperidine in DMF. After the reaction mixture was shaken for 30 min at room temperature. This deprotection step was repeated again and then washed with DMF, Methanol, then DCM. A solution of hydrazine carbamoyl chloride (4 equiv.), HOBt (4 equiv.), and DIG (4 equiv.) in DMF was added to the resin. After the reaction mixture was shaken for 12 hours at room temperature, the resin was washed with DMF, MeOH, and then DCM. Step 4 To the resin swollen by DMF before reaction was added 25% piperidine in DMF. After the reaction mixture was shaken for 30 min at room temperature. This deprotection step was repeated again and then washed with DMF, Methanol, then DCM. To the resin swollen by DCM before reaction was added R,-isocynate (5 equiv.) in DCM. After the reaction mixture was shaken for 12 hours at room temperature the resin was washed with DMF, MeOH, then DCM. StepS The resin was treated with formic acid (1.2 mL each well) for 18 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed .under reduced pressure using SpeedVac [SAVANT] to give the product as oil. These products were diluted with 50% water/acetonitrile and then lyophilized after freezing. Table 3 shows a [4,3,0] Reverse turn mimetics library which can be prepared according to the present invention, of which representative preparation is given in Example 5. [Table 3] The [4,3,0] Reverse turn mimetics library (Table Remove) In a further aspect of this invention, methods for screening the libraries for bioactivity and isolating bioactive library members are disclosed. The libraries of the present invention were screened for bioactiviry by various techniques and methods. In general, the screening assay may be performed by (1) contacting the mimetics of a library with a biological target of interest, such as a receptor, to allow binding between the mimetics of the library and the target to occur, and (2) detecting the binding event by an appropriate assay, such as the calorimetric assay disclosed by Lam et al. (Nature 354:82-84, 1991) or Griminski et al. (Biotechnology 12:1008-1011, 1994) (both of which are incorporated herein by reference). In a preferred embodiment, the library members are in solution and the target is immobilized on a solid phase. Alternatively, the library may be immobilized on a solid phase and may be probed by contacting it with the target in solution. Table 4 below shows compounds for bioactivity test selected from the library of the present invention and ICJO values thereof, which are measured by the Reporter gene assay as described in Example 6. [Table 4] ICso(jiM) of Selected Library Compounds (Table Remove) It is found in the present invention that the compound of general formula (I), especially the compound of general formula (VI) can inhibit GBP-mediated transcriptional activation in cancer cells due to its specific binding to CBP, and it is supported by immunoprecipitation of CBP of SW480 cells with the compound of the present invention. The compound of the present invention can also inhibit the survivin expression in SW480 cells, and therefore, inhibit the oncogenic activity in cancer cells. The compound of the present invention can be used for inhibiting cancer cells, and thus, would be useful for the regulation of cell growth. Supporting such results, the compound of the present invention further shows that it can induce the caspase-3 activation in SW480 cells, and therefore, induce the apoptotic activity in cells. The compound of the present invention can be also advantageously used for inducing apoptosis in cells. To confirm the oncogenic activity in cancer cell in invitro MTS cytotoxicity assay was tested by following method. Cytotoxicity test SW480 or HCT116 cells were placed into 96 well microplate (104cells/well) and incubated for 24 hours at 37 °C. The cells were treated with TCF4 compound at various concentrations for 24 hours. 20 ul of MTS solution (Promega) was added into each well and incubated for 2 hours at 37 °C. Cell viability was measured by reading the absorbance at 490nm using microplate reader (Molecular Device) and cytotoxicity of a compound at each concentration was calculated. Growth Inhibition assay SW480 or HCT116 cells were placed into 96 well microplate (104cells/well) and incubated for 24 hours at 37 °C. 20 ul of [3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt](MTS) solution (Promega) was added into each well and the absorbance after 2 hour incubation at 37 °C (negative control) was read. And then, the cells were treated with TCF4 compound at various concentrations for 48 hours. 20 u,l of MTS solution (Promega) was added into each well and incubated for 2 hour at 37 °C. Cell viability was measured by reading the absorbance at 490nm using a microplate reader (Molecular device) and cytotoxicity of a compound at each concentration was calculated. The results of oncogenic activity for selected library compounds were shown in the Table 5. (Table Remove) In another aspect of the present invention, a pharmaceutical composition containing the compound having the general formula (I), especially the compound of general formula (VI) is disclosed. For the preparation of the pharmaceutical composition containing the present compounds, a skilled person in the art can use publicly known knowledge and techniques which are known in the pertinent art. Generally known varieties of carriers and other additives are used for the preparation of the composition of the present invention. The pharmaceutical compositions of this invention may be administered in standard manner for the disease condition that is desired to be treated, for example by oral, rectal or parenteral administration. For these purposes, the compounds of the present invention may be formulated by means known in the art into a form of, for example, tablets, capsules, aqueous or oily solutions or suspension, (lipid) emulsions, dispersible powders, suppositories, ointments, creams, drops and sterile injectable aqueous or oily solutions or suspensions. A suitable pharmaceutical composition of the present invention is one suitable for oral administration in unit dosage form such as, for example a tablet or capsule which contains from about Img to about Ig of the compound of this invention. In another aspect, a pharmaceutical composition of the present invention is one suitable for intravenous, subcutaneous or intramuscular injection. A patient may receive, for example, an intravenous, subcutaneous or intramuscular dose of aboxit 1 ug/kg to about Ig/kg of the compound of the present invention. The intravenous, subcutaneous and intramuscular dose may be given by means of a bolus injection. Alternatively the intravenous dose may be given by continuous infusion over a period of time. Alternatively a patient will receive a daily oral dose which is approximately equivalent to the daily parenteral dose, the composition being administered 1 to 4 times per day. The following table illustrates representative pharmaceutical dosage forms containing the compound or pharmaceutically-acceptable salt thereof for therapeutics or prophylactic use in humans : (Table Remove) The pharmaceutical composition containing the compound of general formula (I), especially the compound of general formula (VI) can be used for treatment of disorders modulated by Wnt signaling pathway, especially cancer, more especially colorectal cancer. In another aspect of the present invention, a method for inhibiting the growth of tumor cell in a subject in which the method comprises administering to a tumor cell a safe and effective amount of the compounds of the present invention is disclosed. The composition containing such compounds also can be used for the inhibition of tumor cells. Thus, this method can be useful to treat cancer in a mammalian subject. It can be advantageously used for treating colorectal cancer. In another aspect of the present invention, a method for treating a disorder modulated by Wnt signaling pathway in which the method comprises administering to a patient a safe and effective amount of the compounds having general formula (I), especially the compound of general formula (VI) is disclosed. Pharmaceutical composition containing the compound of the present invention can be also used for this purpose. In this connection, it is found in the present invention that the compounds having general formula (I), especially the compound of general formula (VI) or the pharmaceutical composition containing thereof can be useful for the treatment of disorder modulated by TCF4 - p catenin - CBP complex, which is believed to be responsible for initiating the overexpression of cancer cells related to Wnt signaling pathway. Thus, it is another aspect of the present invention to provide a method for the treatment of disorder modulated by TCF4 - p catenin - CBP complex, using the compounds having the general formula (I), especially the compound of general formula (VI). Further, because the treatment of cancer is also closely related to inducing apoptosis in cancer cells in a subject, the present invention is also directed to a method of inducing apoptosis in cancer cells using the compounds of general formula (I), especially the compound of general formula (VI). It has been known from previous art that 5-FU [Fluorouracil; 5-fluoro-2,4(lH, 3H)-pyrimidinedione] can induce apoptosis in cultured oral cancer cells (D. Tong et al., Oral Oncology 36, 2000 236-241). Further, it is also known that colon cancer has a sensitivity to 5-FU (D. Arango et al., Cancer Research 61, 2001 4910-4915). In the present invention, therefore, the combination of 5-FU having established anti-cancer activity and the compounds of formula (I), especially the compound of general formula (VI) of the present invention is prepared and tested against SW480 cell lines. As a result, it is found that the combination of 5-FU with the compounds of the present invention, especially TCF4 compound, has a remarkable effect for inhibiting cancer cell growth such as SW480 cells. Therefore, it is yet another aspect of the present invention to provide a method of treating cancer, which comprises administering to a subject a safe and effective amounts of the compound having formula (I) of Claim 1, especially the compound of general formula (VI), together with other anti-cancer agent such as 5-Fu. Compounds of the present invention have been shown to inhibit the expression of survivin. Blanc-Brude et al, Nat. Medicine 8:987 (2002), have shown that survivin is a critical regulator of smooth muscle cell apoptosis which is important in pathological vessel-wall remodeling. Accordingly, another aspect of the present invention provides a method of treating or preventing restenosis associated with angioplasty comprising administering to a subject in need thereof a safe and effective amount of a reverse-turn mimetic of the present invention. In one embodiment the invention treats the restenosis, i.e., administration of a reverse-turn mimetic of the present invention to a subject having restenosis achieves a reduction in the severity, extent, or degree, etc. of the restenosis. In another embodiment the invention prevents the restenosis, i.e., administration of a reverse-turn mimetic of the present invention to a subject that is anticipated to develop new or additional restenosis achieves a reduction in the anticipated severity, extent, or degree, etc. of the restenosis. Optionally, the subject is a mammalian subject. Compounds of the present invention have been shown to inhibit TCF/B-catenin transcription. Rodova et al, J. Biol. Chem. 277:29577 (2002), have shown that PKD-1 promoter is a target of the B-catenin/TCF pathway. Accordingly, another aspect of the present invention provides a method of treating or preventing polycystic kidney disease comprising administering to a subject in need thereof a safe and effective amount of a reverse-turn mimetic of the present invention. In one embodiment the invention treats the polycystic kidney disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject having polycystic kidney disease achieves a reduction in the severity, extent, or degree, etc. of the polycystic kidney disease. In another embodiment the invention prevents polycystic kidney disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject that is anticipated to develop new or additional polycystic kidney disease achieves a reduction in the anticipated severity, extent, or degree, etc. of the polycystic kidney disease. Optionally, the subject is a mammalian subject. Compounds of the present invention have been shown to inhibit the expression of Wnt signaling. Hanai et al, J. Cell Bio. 158:529 (2002), have shown that endostatin, a known anti-angiogenic factor, inhibits Wnt signaling. Accordingly, another aspect of the present invention provides a method of treating or preventing aberrant angiogenesis disease comprising administering to a subject in need thereof a safe and effective amount of a reverse-turn mimetic of the present invention. In one embodiment the invention treats the aberrant angiogenesis disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject having aberrant angiogenesis disease achieves a reduction in the severity, extent, or degree, etc. of the aberrant angiogenesis disease. In another embodiment the invention prevents aberrant angiogenesis disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject that is anticipated to develop new or additional aberrant angiogenesis disease achieves a reduction in the anticipated severity, extent, or degree, etc. of the aberrant angiogenesis disease. Optionally, the subject is a mammalian subject. Compounds of the present invention have been shown to inhibit the expression of Wnt signalling. Sen et al, P.N.A.S. (USA) 97:2791 (2000), have shown that mammals with rheumatoid arthritis demonstrate increased expression of Wnt and Fz in RA synovia! tissue. Accordingly, another aspect of the present invention provides a method of treating or preventing rheumatoid arthritis disease comprising administering to a subject in need thereof a safe and effective amount of a reverse-turn mimetic of the present invention. In one embodiment the invention treats the rheumatoid arthritis disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject having rheumatoid arthritis disease achieves a reduction in the severity, extent, or degree, etc. of the rheumatoid arthritis disease. In another embodiment the invention prevents rheumatoid arthritis disease, i.e., administration of a reverse-turn mimetic of the present invention to a subject that is anticipated to develop new or additional rheumatoid arthritis disease achieves a reduction in the anticipated severity, extent, or degree, etc. of the rheumatoid arthritis disease. Optionally, the subject is a mammalian subject. Compounds of the present invention have been shown to inhibit the expression of Wnt signalling. Uthoff et al, Int. J. Oncol. 19:803 (2001), have shown that differential upregulation of disheveled and fz (Wnt pathway molecules) occurs in ulcerative colitis (compared to Chron's disease patients). Accordingly, another aspect of the present invention provides a method of treating or preventing ulcerative colitis comprising administering to a subject in need thereof a safe and effective amount of a reverse-rum mimetic the present invention. In one embodiment the invention treats the ulcerative colitis, i.e., administration of a reverse-turn mimetic of the present invention to a subject having ulcerative colitis achieves a reduction in the severity, extent, or degree, etc. of the ulcerative colitis. In another embodiment the invention prevents ulcerative colitis, i.e., administration of a reverse-turn mimetic of the present invention to a subject that is anticipated to develop new or additional ulcerative colitis achieves a reduction in the anticipated severity, extent, or degree, etc. of the ulcerative colitis. Optionally, the subject is a mammalian subject. BEST MODE CARRYING OUT THE INVENTION The following non-limiting examples illustrate the compound, composition, and methods of use of this invention. EXAMPLES Preparation Example 1 : Preparation of (Ar-Fmoc-//'-R3-hydrazino)-acetic acid (1) Preparation of JV-Fmoc-7V-Methyl Hydrazine H H 2 L, two-neck, round-bottomed-flask was fitted with a glass stopper and a calcium tube. A solution of methylhydrazine sulfate (20 g, 139 mmol) in THF (300 mL) was added and a solution of DiBoc (33 g, 153 mmol) in THF was added. Saturated sodium bicarbonate aqueous solution (500mL) was added dropwise via addition funnel over 2 hours with vigorous stirring. After 6 hours, A solution of Fmoc-Cl (39 g, 153 mmol) in THF was added slowly. Resulting suspension was stirred for 6 hours at 0 °C. The mixture was extracted with EA (500 mL) and the organic layer was retained. The solution was dried with sodium sulfate and evaporated in vacua. The next step was proceeded without purification. 1 L, two-necked, round-bottom-flask was fitted with a glass stopper and a calcium tube. A solution of reaction mixture in MeOH (SOOmL) was added and a cone. HC1 (30 mL, 12 N) was added slowly via addition funnel with magnetic stirring in ice water bath and stirred overnight. The mixture was extracted with EA (1000 mL) and the organic layer was retained. The solution was dried with sodium sulfate and evaporated in vacuo. The residue was purified crystallization with n-hexane and EA to give product (32.2 g, 83 %). 'HNMR (DMSO-D6) 6 7.90-7.88 (d, J=6 Hz, 2H,), 8 7.73-7.70 (d, J=9 Hz, 2H,), 7.44-7.31 (m, 4H), 4.52-4.50 (d, 7=6 Hz, 2H), 4.31-4.26 (t, J=6 Hz, 1H), 2.69 (s, 1H) (2) Preparation of (N-fmoc-N -methyl-hydrazino)-acetic acid t-butyl ester Q Fnioc^ XNV H 1 L, two-necked, round-bottom-flask was fitted with a glass stopper and reflux condenser connected to a calcium tube. A solution of W-Fmoc-N'-Methyl-Hydrazine (20 g, 75 mmol) in toluene (300 mL) was added, A solution of t-butylbromo acetate (22 g, 111 mrnol) in toluene (50mL) was added slowly. Cs2C03 (49 g, 149 mmol) was added slowly. Nal (11 g, 74 mmol) was added slowly with vigorous stirring. The reaction mixture was stirred at reflux temperature over 1 day. A mixture was filtered and extracted the organic layer with ethyl acetate[EA] (500 mL). The solution was dried with sodium sulfate and evaporated in vacua. The product was purified by chromatography with haxane : EA = 2 :1 solution to give product (19.8 g, 70 %). 'H-NMR (CDCl3-d) 8 7.78-7.75 (d, J=9 Hz, 2H,), 8 7.61-7.59 (d, J=6 Hz, 2H,), 7.43-7.26 (m, 4H), 4.42-4.40 (d, J=6 Hz, 2H), 4.23 (b, IH), 3.57 (s, 2H), 2.78 (s, 3H), 1.50(s,9H) (3) Preparation of (Ar-Fmoc-^V'-methyl-hydrazino)-acetic acid o OH H 1 L, two-neck, round-bottomed-flask was fitted with a glass stopper and reflux condenser connected to a calcium tube. (Ar-Fmoc-Ar'-methyl-hydrazino)-acetic acid t-butyl ester (20 g, 52 mmol) was added. A solution of HC1 (150 mL, 4 M solution in dioxane) was added slowly with vigorous stirring in an ice water bath. The reaction mixture was stirred at RT over 1 day. The solution was concentrated completely under reduced pressure at 40 °C. The saturated aq. NaHCO3 solution (100 mL) was added and the aqueous layer was washed with diethyl ether (100 mL). The cone. HC1 was drdpwised slowly at 0 °C (pH 2-3). The mixture was extracted and the organic layer was retained (500 mL, MC). The solution was dried with sodium sulfate and evaporated in vacua. The residue was purified by recrystallization with n-hexane and ethyl acetate to give product (12 g, 72 %). 'H-NMR (DMSO-d6) 6 12.38 (s, IH), 8.56 (b, IH), 7.89-7.86 (d, J=9 Hz, 2H,), 5 7.70-7.67 (d, J=9 Hz, 2H,), 7.43-7.29 (m, 4H), 4.29-4.27 (d, .7=6 Hz, 2H), 4.25-4.20 (t, .7=6 Hz, IH), 3.47 (s, 2H), 2.56 (s, 3H) Preparation Example 2 : Preparation of (7V-Moc-Ar'-R7-hydrazino)-acetic acid (1) Preparation of (A^-Methoxycarbonyl-hydrazino)-acetic acid ethyl ester H The methyl carbazate (50g, 0.55mol) was dissolved in DMF (300ml), and then ethyl bromoacetate (68ml, 0.555mol), potassium carbonate (77g, 0.555mol) were added to the reaction vessel. The mixture was warmed to 50°C for Shours. After the reaction was completed, the mixture was filtered, and diluted with EtOAc, and washed with brine (3 times). The crude product was purified by column (eluent : Hex/EtOAc = 4/1). Pdt : 72g (colorless oil) (2) [N-R^-A^-methoxycarbonyl-hydrazinoJ-acetic acid ethyl ester 0 R7 0 The ethyl ester (lOg, 0.05 mol) , potassium carbonate (6.9g, O.OSmol), and R3-bromide (14.1g, 0.06mol) were dissolved in DMF (200ml), and The mixture was warmed to 50°C for 5hours. After the reaction was completed, the mixture was filtered, and diluted with EA, and washed with brine (3 times). The crude product was purified by Chromatography (eluent : Hex/EtOAc = 4/1). (3) [A^R^AP-methoxycarbonyl-hydrazmol-acetic acid R7 H The alkylated ethyl ester (9.5g, 0.03mol) was dissolved in THF/water (1/1, ml), and added 2N NaOH (28.3ml) solution at 0 °C. The mixture was stirred at RT for 2 hours. After the starting ester was not detected on UV, the solution was diluted with EA, then separated. The aqueous layer was acidified to pH 3~4 by IN HC1, and the compound was extracted by DCM (3 times). The combined organic layer was dried over MgSO4, and evaporated to give a yellow solid. EXAMPLE 1 (1) Preparation of A^-Moc-AT-benzyl-hydrazinoglycrne 0 Bn (Figure Remove) Her This compound was prepared according to literature procedure. (Cheguillaume et.sL,$ynfett2000,3,331) (2) Preparation of l-Methoxycarbonyl-2,8-dibenzyl-6-methyl-4,7-dioxo-hexahydro-pyrazino[2,l-c][l,2,4]triazine (Figure Remove) The bromoacetal resin (60 mg, 0.98 iranol/g) and a solution of benzyl amine in DMSO (2.5 ml, 2 M) were placed in vial with screw cap. The reaction mixture was shaken at 60 °C using rotating oven [Robbins Scientific] for 12 hours. The resin was collected by filtration, and washed with DMF, then DCM. A solution of Fmoc-alanine (4 equiv.), HATU [PerSeptive Biosystems] (4 equiv.), and DIEA (4 equiv.) in NMP (Advanced ChemTech) was added to the resin. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. To the resin was added 20% piperidine in DMF. After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. A solution of A^-Moc-A^-benzyl-hydrazinoglycine (4 equiv.), HOBT [Advanced ChemTech] (4 equiv/), and DIG (4 equiv.) in DMF was added to the resin prepared above. After the reaction mixture was shaken for 3 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then MeOH. The resin was dried in vacuo at room temperature The resin was treated with formic acid (2.5 ml) for 18 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under reduced pressure to give the product as an oil. 'H-NMR (400 MHz, CDC13) 5 ppm; 1.51 (d, 3H), 2.99 (m, 1H), 3.39 (d, 1H), 3.69 (m, 1H), 3.75 (m, 1H), 3.82 (s, 3H), 4.02 (d, 1H), 4.24 (d, 1H), 4.39 (d, 1H), 4.75 (d, 1H), 5.14 (q, 1H), 5.58 (dd, 1H), 7.10-7.38 (m, 10H). EXAMPLE 2 (1) Preparation of//-Fmoc-//-methyl-hydrazinocarbonyl chloride (Figure Remove) An ice-cooled biphasic mixture of N-Methyl hydrazine carboxylic acid 9H-Fluoren-9-ylmethyl ester (107 mg, 0.4 mmol) in 15 ml of CH2C12 and 15 ml of saturated aq. NaHC03 was rapidly stirred while a 1.93 M phosgene in toluene (1.03 ml, 2 mmol) was added as a single portion. The reaction mixture was stirred for 30 min, the organic phase was collected, and the aqueous phase was extracted with CH2C12. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford 128 mg (97 %) of carbamoyl chloride as a foamy solid. [Caution: Phosgene vapor is highly toxic. Use it in a hood] This product was used for the following solid'phase synthesis without further purification. (2) Preparation of 2,5-Dunethyl-7-ben2yl-3,6-dioxo-hexahydro-[l,2,4]triazolo[4,5-a]pyrazine-l-carboxylic acid benzylamide (Figure Remove) The bromoacetal resin (30 mg, 0.98 mmol/g) and a solution of benzyl amine in DMSO (1.5 ml, 2 M) were placed in vial with screw cap. The reaction mixture was shaken at 60 °C using rotating oven [Robbins Scientific] for 12 hours. The resin was collected by filtration, and washed with DMF, then DCM. A solution of Fmoc-alanine (3 equiv.), HATU [PerSeptive Biosystems] (3 equiv.), and DIEA (3 equiv.) in NMP (Advanced ChemTech) was added to the resin. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. To the resin was added 20% piperidine in DMF. After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. A solution of 7^-Fmoc-JV-methyl-hydrazinocarbonyl chloride (5 equiv.) obtained in the above step (1), DIEA (5 equiv.) in DCM was added to the resin prepared above. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and DMF. To the resin was added 20% piperidine in DMF (10 ml for 1 g of the resin). After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. The resin was treated with a mixture of benzyl isocyanate (4 equiv.) and DEEA (4 equiv.) in DCM for 4 hours at room temperature. Then, the resin was collected by filteration and washed with DMF, DCM, and then MeOH. The resin was dried in vacua at room temperature. The resin was treated with formic acid for 14 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under reduced pressure to give the product as an oil. 'H-NMR (400 MHz, CDC13) 8 ppm; 1.48 (d, 3H), 2.98 (s, 3H), 3,18 (m, 1H), 3.46 (m, 1H), 4.37-4.74 (m, 5H), 5.66 (dd, 1H), 6.18 (m, 1H), 7.10-7.40 (m, 10H). EXAMPLES Preparation of 2>5,7-Trimethyl-3,6-dioxo-hexahydro-[l,2,4]triazolo[4,5-a]pyrazine-l-carboxylic acid benzylamide The title compound is prepared according to the same procedure with Example 2. 'H-NMR (400 MHz, CDC13) 8 ppm; 1.48 (d, 3H), 2.99 (s, 3H), 3.03 (s, 3H), 3.38 (m, 1H), 3.53 (dd, 1H), 4.36 (dd, 1H), 4.52 (q, 1H), 4.59 (dd, 1H), 5.72 (dd, 1H), 6.19 (br.t, 1H), 7.10-7.38 (m,5H). EXAMPLE 4 Preparation of 2-Methyl-5-(p-hydroxyphenymiethyl)-7-naphthyhnethyl-3,6-dioxo-hexahydrQ-[l,2,4]triazolo[4,5-a]pyra2ine-l-carboxylic acid benzylamide The bromoacetal resin (30 mg, 0.98 mmol/g) and a solution of naphthylmethyl amine in DMSO (1.5 ml, 2 M) were placed in vial with screw cap. The reaction mixture was shaken at 60 °C using rotating oven [Robbins Scientific] for 12 hours. The resin was collected by filtration, and washed with DMF, then DCM. A solution of Fmoc-Tyr(OBut)-OH (3 equiv.), HATU [PerSeptive Biosystems] (3 equiv.), and DIEA (3 equiv.) in NMP (Advanced ChemTech) was added to the resin. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. To the resin was added 20% piperidine in DMF. After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by nitration and washed with DMF, DCM, and then DMF. A solution of AP-Fmoc-N-methyl-hydrazinocarbonyl chloride (5 equiv.), DIEA (5 equiv.) in DCM was added to the resin prepared above. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and DMF. To the resin was added. 20% piperidine in DMF (10 ml for 1 g of the resin). After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. The resb was treated with a mixture of benzyl isocyanate (4 equiv.) and DIEA (4 equiv.) hi DCM for 4 hours at room temperature. Then, the resin was collected by alteration and washed with DMF, DCM, and then MeOH. The resin was dried in vacuo at room temperature. The resin was treated with formic acid for 14 hours at room temperature. After the resin was removed by filtration, the filtrate was condensed under reduced pressure to give the product as an oil. 'H-NMR (400 MHz, CDC13) 8 ppm; 2.80-2.98 (m, 5H), 3.21-3.37 (m, 2H), 4.22-4.52 (m, 2H), 4.59 (t, 1H), 4.71 (d, 1H), 5.02 (dd, 1H), 5.35 (d, 1H), 5.51 (d, 1H), 6.66 (t, 2H), 6.94 (dd, 2H), 7.21-8.21 (m, 12H). EXAMPLE 5 Preparation of 2-Methyl-6-(g-hydroxyphenyhnethyl)-8-naphthyl-4,7-dioxo-hexahydro-pyra2ino[2>l-c][l,2>43triazine-l-carboxylic acid benzylamide The bromoacetal resin (60 mg, 0.98 mmol/g) and a solution of naphthyl amine in DMSO (2.5 ml, 2 M) were placed in vial with screw cap. The reaction mixture was shaken at 60 °C using rotating oven [Robbins Scientific] for 12 hours. The resin was collected by filtration, and washed with DMF, then DCM. A solution of Fmoc- Tyr(OBut)-OH (4 equiv.), HATU [PerSeptive Biosystems] (4 equiv.), and DIEA (4 equiv.) in NMP (Advanced ChemTech) was added to the resin. After the reaction mixture was shaken for 4 hours at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. To the resin was added 20% piperidine in DMF. After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. A solution of //-Fmoc-A^-benzyl-hyrazinoglycine (4 equiv.), HOBT [Advanced ChemTeeh] (4 equiv.), and DIG (4 equiv.) in DMF was added to the resin prepared above. After the reaction mixture was shaken for 3 hours at room temperature, the resin was collected by filtration and washed with DMF, and then DCM. To the resin was added 20% piperidine in DMF (10 ml for 1 g of the resin). After the reaction mixture was shaken for 8 min at room temperature, the resin was collected by filtration and washed with DMF, DCM, and then DMF. The resin was treated with a mixture of benzyl isocyanate (4 equiv.) and DIEA (4 equiv.) in DCM for 4 hours at room temperature. Then, the resin was collected by filteration and washed with DMF, DCM, and then MeOH. After the resin was dried in vacuo at room temperatur, the resin was treated with formic acid (2.5 ml) for 18 hours at room temperature. The resin was removed by filtration, and the filtrate was condensed under reduced pressure to give the product as an oil. 'H-NMR (400 MHz, CDC13) 5 ppm; 2.73 (s, 3H), 3.13 (d, 1H), 3.21-3.38 (m, 3H), 3.55 (d, 1H), 3.75 (t, 1H), 4.22 (dd, 1H), 4.36 (dd, 1H), 4.79 (d, 1H), 5.22 (t, 1H), 5.47 (m, 2H), 6.68 (d, 2H), 6.99 (d, 2H), 7.21-8.21 (m, 12H); MS (m/z, ESI) 564.1 (MET) 586.3 EXAMPLE 6 Bioassay for the measurement of ICJD against SW480 cells and Cytotoxicity test on the cell lines were proceeded by following methods: Test compound has been prepared in the Example 4 (Figure Remove) Reporter Gene Assay SW480 cells were transfected with the usage of Superfect™ transfect reagent (Qiagen, 301307). Cells were trypsinized briefly 1 day before transfection and plated on 6 well plate (5 x 105 cells/well) so that they were 50-80% confluent on the day of transfection. Four micrograra (TOPFlash) and one microgram (pRL-nuH) of DNAs were diluted in 150 |.il of serum-free medium, and 30 ul of Superfect™ transfect reagent was added. The DNA-Superfect mixture was incubated at room temperature for 15 min, and then, 1 ml of 10 % FBS DMEM was added to this complex for an additional 3 hours of incubation. While complexes were forming, cells were washed with PBS twice without antibiotics. The DNA-Superfect™ transfect reagent complexes were applied to the cells before incubating at 37 °C at 5 % CO2 for 3 hours. After incubation, recovery medium with 10 % FBS was added to bring the final volume to 1.18 ml. After 3 hours incubation, the cells were harvested and reseeded to 96 well plate (3 x 104 cells/well). After overnight incubation at 37 °C at 5 % CO2) the cells were treated with the test compound for 24 hours. Finally, the activity was checked by means of luciferase assay (Promega,E1960). Fig. 1 illustrates the results of the measurement of IC50 of the above compound for SW480 cells. Sulforhodamine B (SRB) assay Growth inhibitory effect of the above compound on the cells listed below was measured by the sulforhodamine B assay. SW480 cells in 100 ul media were plated in each well of 96-well plate and allowed to attach for 24 hours. Compound was added to the wells to produce the desired final concentrations, and the plates were incubated at 37 °C for 48 hours. The cells were then fixed by gentle addition of 100 ul of cold (4 °C) 10% trichloroacetic acid to each well, followed by incubation at 4 °C for 1 hour. Plates were washed with deionized water five times and allowed to air dry. The cells were then stained by addition of 100 ul SRB solution (0.4% SRB(w/v) in 1% acetic acid (v/v)) to wells for 15 min. After staining, the plates were quickly washed five times with 1% acetic acid to remove any unbound dye, and allowed to air dry. Bound dye was solubilized with 10 mmol/L Tris base (pH 10.5) prior to reading the plates. The optical density (OD) was read on a plate reader at a wavelength of 515nm with Molecular Device. Inhibition of growth was expressed as relative viability (% of control) and GI50 was calculated from concentration-response curves after log/probit transformation. [Table 6] In vitro cyctotoxicity (SRB) assay of the compound obtained in Example 4 (Table Remove) It will be appreciated that, although specific embodiments of the invention have been described hereb for the purposes of illustration, various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the invention is not limited except by the appended claims. INDUSTRIAL APPLICABILITY The compounds of the invention which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins, can inhibit the expression of survivin, TCF/B-catenin transcription, and the expression of Wnt signaling. Therefore, the present invention can provide a pharmaceutical composition and/or a method for inhibiting the growth of tumor cell in a mammalian subject, for treating cancer in combination with other anti-neoplastic agents, for treating or preventing diseases such as restenosis associated with angioplasty, polycystic kidney disease, aberrant angiogenesis disease, rheumatoid arthritis disease and ulcerative colitis, as well as a method of identifying a biologically active compound, and a library of compounds. WE CLAIM: 1.A reverse turn mimetic having the following general formula: (Formula Removed) wherein R1, R2, R3, R4, R5, R6, and R7, are the same or different and independently selected from C1-12 alkyl, C6-12 aryl and C7-12 arylalkyl, either substituted or unsubstituted with one or more of the following chemical moieties: -OH, -OR, -COOH, -COOR, -CONH2, -NH2, -NHR, -NRR, -SH, -SR, -SO2R, -SO2H, -SOR and halogen (including F, CI, Br and I), wherein each occurrence of R is independently selected from straight chain or branched, cyclic or noncyclic, substituted or unsubstituted, saturated or unsaturated C1-12 alkyl, C6-12 aryl and C7-12 arylalkyl moieties; naphthalene, heterocyclic compounds such as thiophene, pyrrole, furan, imidazole, oxazole, thiazole, pyrazole, 3-pyrroline, pyrrolidine, pyridine, pyrimidine, purine, quinoline, isoquinoline and carbazole, heteroalkyl derivatives of the alkyl portion of the lower chain alkyl and aralkyl moieties, including (but not limited to) alkyl and aralkyl phosphonates and silanes. The compound as claimed in claim 1, wherein R1, R2, R3, R4, R5 and R6 are independently selected from the group consisting of aminoC2-5alkyl, C1-3alkoxy, phenyl, substituted phenyl(where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), benzyl, substituted benzyl (where the substituents on the benzyl are independently selected from one or more of amino, amidino, guanidino, hydrazino, Valkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), naphthyl, substituted naphthyl(where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), bis-phenyl methyl, substituted bis-phenyl methyl (where the substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, Ci-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1- 3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), pyridyl, substituted pyridyl (where the substituents are independently selected from one or more of amino amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl ), pyridylCi-4alkyl, substituted pyridylC1-4alkyl (where the pyridine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), pyrimidylC1-4alkyl, substituted pyrimidylC1-4alkyl (where the pyrimidine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy or nitro, carboxy, cyano, sulfuryl or hydroxyl), triazin-2-yl-C1-4alkyl, substituted triazin-2-yl-C1-4alkyl (where the triazine substituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), imidazolylC1-4alkyl, substituted imidazolylC1-4alkyl (where the imidazole sustituents are independently selected from one or more of amino, amidino, guanidino, hydrazino, C1-4alkylamino, C1-4dialkylamino, halogen, perfluoro C1-4alkyl, C1-4alkyl, C1-3alkoxy, nitro, carboxy, cyano, sulfuryl or hydroxyl), imidazolinylC1-4alkyl, N-amidinopiperazinyl-N-Co-4alkyl, hydroxyC2-5alkyl, C1-5alkylaminoC2-salkyl, C1-5dialkylaminoC2-5alkyl, N-amidinopiperidinylC1-4alkyl and 4-aminocyclohexylCo-2alkyl. 3. The compound as claimed in claim 1, wherein the compound has the following general formula (VI): (Formula Removed) wherein, Ra is a bicyclic aryl group having 8 to 11 ring members, which may have 1 to 3 heteroatoms selected from nitrogen, oxygen or sulfur, and Rb is a monocyclic aryl group having 5 to 7 ring members, which may have 1 to 2 heteroatoms selected from nitrogen, oxygen or sulfur, and aryl ring in the compound may have one or more substituents selected from a group consisting of halide, hydroxy, cyano, lower alkyl, and lower alkoxy group. 4. The compound as claimed in claim 3, wherein Ra is naphthyl, quinolinyl or isoquinolinyl group, and Rb is phenyl, pyridyl or piperidyl, all of which may be substituted with one or more substituents selected from a group consisting of halide, hydroxy, cyano, lower alkyl, and lower alkoxy group. 5. The compound as claimed in claim 3, wherein Ra is naphthyl, and Rb is phenyl, which may be substituted with one or more substituents selected from a group consisting of halide, hydroxy, cyano, lower alkyl, and lower alkoxy group. 6. A pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable carrier. 7. The pharmaceutical composition as claimed in claim 6, in which the composition comprises a safe and effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.

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