INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

Abstract: The present invention comprises low molecular weight peptidyl compounds that inhibit the farnesyl-protein transferase. Furthermore, these compounds differ from the mono- or dipeptidyl analogs previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Description: TITLE OF THE INVENTION INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE RELATED APPLICATION The present patent application is a continuation-in-part application of copending application Serial No. 08/468,160, filed June 6, 1995. BACKGROUND OF THE INVENTION The Ras protein is part of a signalling pathway that links cell surface growth factor receptors to nuclear signals initiating cellular proliferation. Biological and biochemical studies of Ras action indicate that Ras functions like a G-regulatory protein. In the inactive state, Ras is bound to GDP. Upon growth factor receptor activation Ras is induced to exchange GDP for GTP and undergoes a conformational change. The GTP-bound form of Ras propagates the growth stimulatory signal until the signal is terminated by the intrinsic GTPase activity of Ras, which returns the protein to its inactive GDP bound form (D.R. Lowy and D.M. Willumsen, Ann. Rev. Biochem. 62:851-891 (1993)). Mutated ras genes are found in many human cancers, including colorectal carcinoma, exocrine pancreatic carcinoma, and myeloid leukemias. The protein products of these genes are defective in their GTPase activity and constitutively transmit a growth stimulatory signal. Ras must be localized to the plasma membrane for both normal and oncogenic functions. At least 3 post-translational modifications are involved with Ras membrane localization, and all 3 modifications occur at the C-terminus of Ras. The Ras C-terminus contains a sequence motif termed a "CAAX" or "Cys-Aaa^-Aaa^-Xaa" box (Cys is cysteine, Aaa is an aliphatic amino acid, the Xaa is any amino acid) (Willumsen et al, Nature 370:583-586 (1984)). Depending on the specific sequence, this motif serves as a signal sequence for the enzymes famesyl-protein transferase or geranylgeranyl-protein transferase, which catalyze the alkylation of the cysteine residue of the CAAX motif with a C15 or C20 isoprenoid, respectively. (S. Clarke., Ann. Rev. Biochem. 61 :355-386 (1992); W.R. Schafer and J. Rine, Ann. Rev. Genetics 30:209- 237 (1992)). The Ras protein is one of several proteins that are known to undergo post-translational farnesylation. Other farnesylated proteins.include the Ras-related GTP-binding proteins such as Rho, fungal mating factors, the nuclear larnins, and the gamma subunit of transducin. James, et al., /. Biol Chem. 269, 14182 (1994) have identified a peroxisome associated protein Pxf which is also farnesylated. James, et al., have also suggested that there are farnesylated proteins of unknown structure and function in addition to those listed above Inhibition of famesyl-protein transferase has been shown to block the growth of Ras-transformed cells in soft agar and to modify other aspects of their transformed phenotype. It has also been demonstrated that certain inhibitors of famesyl-protein transferase selectively block the processing of the Ras oncoprotein intracellularly (N.E. Kohl et al, Science, 260: 1934-1937 (1993) and G.L. James et al, Science, 260:1937-1942 (1993). Recently, it has been shown that an inhibitor of famesyl-protein transferase blocks the growth of ras- dependent tumors in nude mice (N.E. Kohl et al, Proc. Natl Acad. Sci U.S.A., 97:9141-9145 (1994) and induces regression of mammary and salivary carcinomas in ras transgenic mice (N.E. Kohl et al, Nature Medicine, 1:792-797 (1995). It has also been reported that a famesyl- protein transferase inhibitor inhibits the growth of a broad range of human tumor cell lines, including those that do not have mutant forms of ras (L. Sepp-Lorenzino et al, Cancer Research, 55:5302-5309 (1995)). Indirect inhibition of famesyl-protein transferase in vivo has been demonstrated with lovastatin (Merck & Co., Rahway, NJ) and compactin (Hancock et al, ibid; Casey et al, ibid; Schafer et al, Science 245:379 (1989)). These drugs inhibit HMG-CoA reductase, the rate limiting enzyme for the production of polyisoprenoids including farnesyl pyrophosphate. Famesyl-protein transferase utilizes farnesyl pyrophosphate to covalently modify the Cys thiol group of the Ras CAAX box with a farnesyl group (Reiss et al, Cell, 62:81-88 (1990); Schaber et al, J. Biol. Chem., 265:14701-14104 (1990); Schafer et al, Science, 249:1133-1139 (1990); Manne et al, Proc. Natl Acad. Sci USA, 57:7541-7545 (1990)). Inhibition of farnesyl pyrophosphate biosynthesis by inhibiting HMG-CoA reductase blocks Ras membrane localization in cultured cells. However, direct inhibition of famesyl-protein transferase would be more specific and attended by fewer side effects than would occur with the required dose of a general inhibitor of isoprene biosynthesis. Inhibitors of famesyl-protein transferase (FPTase) have been described in two general classes. The first are analogs of farnesyl diphosphate (FPP), while the second class of inhibitors is related to the protein substrates (e.g., Ras) for the enzyme. The peptide derived inhibitors that have been described are generally cysteine containing molecules that are related to the CAAX motif that is the signal for protein prenylation. (Schaber et al, ibid; Reiss et. al., ibid; Reiss et al, PNAS, 88:132-136 (1991)). Such inhibitors may inhibit protein prenylation while serving as alternate substrates for the famesyl-protein transferase enzyme, or may be purely competitive inhibitors (U.S. Patent 5,141,851, University of Texas; N.E. Kohl et a , Science, 260:1934-1937 (1993); Graham, et al., J. Med. Chem., 37, 725 (1994)). In general, deletion of the thiol from a CAAX derivative has been shown to dramatically reduce the inhibitory potency of the compound. However, the thiol group potentially places limitations on the therapeutic application of FPTase inhibitors with respect to pharmacokinetics, pharmacodynamics and toxicity. Therefore, a functional replacement for the thiol is desirable. It has recently been disclosed that certain tricyclic compounds which optionally incorporate a piperidine moiety are inhibitors of FPTase (WO 95/10514, WO 95/10515 and WO 95/10516). Imidazole-containing inhibitors of farnesyl protein transferase have also been disclosed (WO 95/09001, WO 96/00736 and EP 0 675 112 Al). Substituted di-, tri- tetra- and pentapeptide inhibitors of famesyl-protein transferase have also recently been disclosed (WO 95/12612 and WO 95/11917). It is, therefore, an object of this invention to develop small molecules that do not have a thiol moiety, and that will inhibit famesyl- protein transferase and thus, the post-translational farnesylation of proteins. It is a further object of this invention to develop chemotherapeutic compositions containing the compounds of this invention and methods for producing the compounds of this invention. SUMMARY OF THE INVENTION The present invention comprises low molecular weight peptidyl compounds that inhibit the famesyl-protein transferase. Furthermore, these compounds differ from the mono- or dipeptidyl analogs previously described as inhibitors of famesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production. The compounds of this invention are illustrated by the formula: DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention inhibit the famesyl-protein transferase. In a first embodiment of this invention, the famesyl-protein transferase inhibitors are illustrated by the formula I: wherein: Rla is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2- C20 alkynyl, R*0θ-, Rl lS(0) m -, R10C(O)NR10-, CN, Nθ2, (RlO)2N-C(NRlO)-_ RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl 10C(0)NR10-, c) C 1 -C6 alkyl unsubstituted or substituted by aryl, heterocyclic, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, RlOO-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, N3, -N(Rl )2, or Rl lOC(O)-NRl0- ; Rib is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, RlOO-, RllS(0) m -, CN, NO2, (R 1 0)2N-C(NRlO)-, RlOC(O)-, Rl0θC(O)-, N3 or -N(Rl0) 2 , c) C1-C6 alkyl unsubstituted or substituted by substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic, C3-C10 cycloalkyl, C2-C20 alkenyl, C2-C2O alkynyl, RlOO-, Rl lS(0) m -, CN, (R10) 2 N-C(NR10)-, R10C(O)-, RlOθC(O)-, N3 or -N(Rl ) ; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C2-C2O alkenyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, R 10 O-, Rl lS(0)m-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, R n OC(O)NRl0- and C1-C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R are combined to form - (CH2)s - ; or R2 or R3 are combined with R7 to form a ring such that R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C20 alkenyl, RlOO-, RllS(0)m-, R 10 C(O)NRl0-, CN, N3, (R 10 )2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or RHOC(0)NR1 -, c) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2- C20 alkenyl, halogen, RlOO-, RllS(0) m -, Rl C(0)NRlO-, CN, N02, (R 10 )2N-C(NRlO)-, Rl C(O)-, N3, -N(R1 ) 2 , or RUOC(O)NR10-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; Rl3a and Rl3b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C2O alkenyl, RIOO-, RllS(0)m-, R 10 C(O)NRl0-, CN, N3, (RlO)2N- C(NRlO)-, RlOc(O)-, -N(RlO)2, or RHOC(O)NR10-, c) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2- C20 alkenyl, halogen, Rl4θ-, R1 lS(0) m -, Rl0C(O)NRl0-, CN, N02, (R 10 )2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RUθC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 perfluoroalkyl, allyloxy, F, Cl, Br, RlOO-, RUSCO)!!!-, R 10 C(O)NRl -, CN, Nθ2, R10 2N _C(NR10)-, RlOC(O)-, N3, -N(RlO) , (Rl2) 2 NC(0)- or Rl lOC(O)NRl0_, and c) C1-C6 alkyl unsubstituted or substituted by substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, C2- C20 perfluoroalkyl, F, Cl, Br, RlOO-, RllS(0) m -, RlOC(0)NH-, CN, H2N-C(NH)-, RlOC(O)-, N3, -N(Rl ) 2 , or Rl0θC(O)NH-; R7 is independently selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocycle, d) unsubstituted or substituted C3-C10 cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R8 is selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C20 alkynyl, C1-C20 perfluoroalkyl, allyloxy, F, Cl, Br, Rl O-, R π S(0)m-, R 10 C(O)NRl0-, -S(O)2NRl0 2 , CN, Nθ2, R10 2 N-C(NR1 )-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3- 0 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, C2- C20 perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C20 alkenyl, C2-C2O alkynyl, C2-C2O perfluoroalkyl, F, Cl, Br, Rl O-, RllS(0) m -, R 10 C(O)NRl -, CN, N02, (Rl ) 2 N-C-(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or RllOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by C2-C20 perfluoroalkyl, F, Cl, Br, RlOO-, Rl 1 S(0) m -, Rl c(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, N3, -N(Rl ) 2 , or RHOC(O)NR10- ; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl2)2 forms - (CH2) S - ; Rl4 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkyl substituted with CO2R 1 °, C 1 -C6 alkyl substituted with aryl, C l - C6 alkyl substituted with substituted aryl, C1-C6 alkyl substituted with heterocycle, C1-C6 alkyl substituted with substituted heterocycle, aryl and substituted aryl; A1> A2 and A^ are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, O, -N(R7)-, -S(0)2N(R7)-, -N(R7)S(0)2-, or S(0) m ; A^ is selected from: a bond, O, -N(R7)- or S; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if A* is a bond, n is 0 and A-2 is S(0)m; W is a heterocycle; Z is independently Rl a 2 or O; or the pharmaceutically acceptable salts thereof. In a preferred embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the Formula I: I wherein: Rla is independently selected from: hydrogen or Cl-C6 alkyl; Rib is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, RlOO-, -N(RlO)2 or C2-C6 alkenyl, and c) C1-C6 alkyl unsubstituted or substituted by substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO-, or -N(RlO)2; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substituted or unsubstituted Cl-ClO alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, R 10 O-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, R1 0C(0)NR10- and C1-C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; wherein said substituted group is substituted with 1 or 2 substitutents selected from: F, Cl, Br, CF3, NH2, N(Cl-C6 alkyl)2, Nθ2, CN, (C1-C6 alkyl)0-, -OH, (C1-C6 alkyl)S(0)m-, (C1-C6 alkyl)C(0)NH-, H2N-C(NH)-, (Cl- C6 alkyl)C(O)-, (C1-C6 alkyl)OC(O)-, N3,(Cl-C6 alkyl)OC(0)NH- and C1-C2O alkyl; or R2 or R3 are combined with R7 to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) Cl-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RlOo-, RllS(0)m-, R1°C(0)NR10-, CN, N3, (RlO)2N- C(NRl )-, RlOc(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0-, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, halogen, RlOO-, RHS(0) m -, Rl C(0)NRlO-, CN, N02, (RlO)2N-(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(0)NRIO., and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; Rl3a and R 13b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, halogen, Rl4θ-, Rl lS(0) m -, Rl C(0)NRlO-, CN, N02, (Rl°)2N-(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl -, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, allyloxy, Rl0C(O)NRl0-, CN, N02, (R1°)2N-C(NR10)-, R10C(O)-, -N(RlO)2, (Rl2) 2 NC(0)- or RHOC(O)NR1 -, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, Rl0c(O)NRl -, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(RlO)2, or Rl lOC(O)NRl0-; R7 is independently selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocycle, d) unsubstituted or substituted C3-C10 cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, R10C(0)NR10-, CN, N02, (Rl ) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RllOC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RHOC(O)NR1 -; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RIOQ-, RllS(0)m-, R 10 C(O)NR***0-, CN, N02, (Rl°)2N- C(NRl )-, RlOC(O)-, Rl θC(O)-, -N(RlO) 2 , or RllθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or RllOC(O)NRl0-; RlO is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl2)2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, Cl-C6 alkyl, Cl-C6 alkyl substituted with Cθ2Rl°, C1-C6 alkyl substituted with aryl, Cl- C6 alkyl substituted with substituted aryl, C1-C6 alkyl substituted with heterocycle, Cl-C6 alkyl substituted with substituted heterocycle, aryl and substituted aryl; Al, A2 and A3 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A4 is selected from: a bond, O, -N(R7)- or S; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0) m and V is not hydrogen if Al is a bond, n is 0 and A is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, oxazolyl, isoxazolyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently Rl a 2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; q is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; and t is 3, 4 or 5; or the pharmaceutically acceptable salts thereof. In a further preferred embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the Formula I: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; R b is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, Rl^O- or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, Rl°0-, or -N(Rl ) 2 ; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted Cl-ClO alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, RlOO-, Rl lS(0)m-, Rl0C(O)NRl -, CN, (RlO) 2 N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , RllθC(O)NRl0- and C1-C2O alkyl; or R2 or R are combined with R7 to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RlOO-, Rl lS(0)m-, R1°C(0)NR10-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(Rl )2, or R11OC(O)NR10-, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N02, (RlO)2N-C(NRl )-, RlOC(O)-, N3, -N(RlO)2, or Rl 10C(0)NR10-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic and C3-C 10 cycloalkyl ; Rl3a and R 13b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, Rl4θ-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N02, (Rl°)2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR10-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, allyloxy, RlOC(0)NRlO-, CN, N02, (R1°)2N-C(NR10)-, RlOc(O)-, -N(RlO)2, (Rl )2NC(0)- or RHOC(O)NR10-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, RlOC(0)NRlO-, (RlO) 2 N-C(NRl )-, RlOc(O)-, -N(Rl ) 2 , or Rl lθC(O)NRl0- ; R7 is independently selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocycle, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocycle and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R1 C(O)NR 0-, CN, NO2, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl substituted by Cl -C6 perfluoroalkyl, RlOO-, R10C(O)NR10-, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(Rl )2, or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl°0-, RllS(0)m-, R1°C(0)NR10-, CN, N02, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, -N(Rl )2, or RHθC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl2)2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkyl substituted with Cθ2Rl°, C1-C6 alkyl substituted with aryl, Cl- C6 alkyl substituted with substituted aryl, C1-C6 alkyl substituted with heterocycle, C1-C6 alkyl substituted with substituted heterocycle, aryl and substituted aryl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A is selected from: a bond, O, -N(R7)- or S; A3 is selected from: a bond, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0) m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently Rl a 2 or O; or the pharmaceutically acceptable salts thereof. In another preferred embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the Formula la: la wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, Rl°0- or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, Rl°0-, or R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted Cl-ClO alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, Nθ2, RlOO-, Rl lS(0)m-, R1°C(0)NR10-, CN, (RlO) 2 N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and C1-C20 alkyl; or R2 or R3 are combined with R7 to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RlOO-, RllS(0)m-, R 10 C(O)NR*-*0-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl 10C(0)NR1 -, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, RlOO-, R *** *** S(0) m -, R10C(O)NR10-, CN, N02, (R 10 )2N-C(NR 10 )-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR1 -, and d) Cl-C6 alkyl substituted with an unsubstituted or substituted group selected from substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic and C3-C10 cycloalkyl; Rl3a and Rl3b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substituted by C2-C6 alkenyl, RIOO-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, Rl 0-, RHS(0) m -, Rl0C(O)NRl0-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR10-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl O-, allyloxy, Rl0C(O)NRl0-, CN, N02, (R10)2N-C(NR10)-, RlOc(O)-, -N(RlO)2, (Rl2) 2 NC(0)- or R110C(0)NR10-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, Rl n O-, Rl C(O)NRl0-, (R10) 2 N-C(NR1 )-, RlOc(O)-, -N(RlO)2, or RHθC(O)NRl0-; R7 is independently selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocycle, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocycle and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R1 Π C(O)NR10-, CN, Nθ2, (RlO)2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl substituted by C 1 -C6 perfluoroalkyl, R 1 n O-, RlOC(0)NRlO-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, RllS(0)m-, Rl π C(0)NRl π -, CN, Nθ2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, Rl°0-, Rl lS(0) m -, R1°C(0)NR10-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, RIOOC(O)-, -N(RlO)2, OΓ RHOC(O)NR10-; RIO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl )2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkyl substituted with Cθ2Rl°, C1-C6 alkyl substituted with aryl, Cl- C6 alkyl substituted with substituted aryl, C1-C6 alkyl substituted with heterocycle, C1-C6 alkyl substituted with substituted heterocycle, aryl and substituted aryl; Al and A2 are independently selected from: a bond, -CH=CH-, -CΞC-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A4 is selected from: a bond, O, -N(R7)- or S; A is selected from: a bond, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0) m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; Z is independently Rl a 2 or O; or the pharmaceutically acceptable salts thereof. The preferred compounds of this invention are as follows: N-Allyloxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)acetyl } amino-3 (S)- methylpentanamine N-Naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5- yl)acetyl}amino-3(S)- methyl pentanamine N-Methoxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5-yl)acetyl}amino-3(S)- methyl pentanamine N- Acetyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl } amino-3(S)-methylpentanamine N-Proρionyl-N-naphth-l-ylmethyl-2(S)-{ (l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Methylsulfonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Ethylsulfonyl-N-naphth-l-ylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Methylaminocarbonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4- cyanobenzyl)-lH-imidazol-5-yl)acetyl}amino-3(S)- methylpentanamine N-Propyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol- 5-yl)acetyl }amino-3(S)- methylpentanamine N-3-Chlorobenzyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-(2-Imidazolylmethyl )-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)acetyl } amino-3 (S)- methylpentanamine 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyl)amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyl)amino- N-methyl-N-benzyl propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(t- butoxycarbonyl)amino- N-(2-methylbenzyl) propionamide 2(RS)-{ [l-(Naρhth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(t- butoxycarbonyl)amino- N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(Naρhth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3- amino- N-methyl-N-benzyl propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl}amino-3- amino- N-(2-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(3-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(3-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl}amino-3-(2- methylpropionyl)amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- (phenylacetyl)amino- N-(naphth-l-ylmethyl)propionamide 2(RS)- { [ 1 -(Naρhth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3- (phenylacetyl)amino- N-methyl-N-benzyl) propionamide [ 1 -(Naphth-2-ylmethyl)- 1 H-imidazol-5-yl)]-N-butylacetamide [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)]- N-methyl-N-(3,3- diphenylpropyl)acetamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N-methyl-N-benzyl propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N-(naphth-l-ylmethyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino N-methyl-N-benzyl- propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino N-(naphth- 1 -ylmethyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3- (phenylacetyl)amino - N-methyl-N-benzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3- (acetyl)amino - N-(naphth-l-yl methyl)propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(2- methylpropionyl)amino - N-(naphth-l-ylmethyl) propionamide 2(RS)-{[l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(2- methylpropionyl)amino - N-(naphth-l -ylmethyl) propionamide N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yllacetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycine isopropylamide N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl] -N-( 1 -naphthylmethyl)glycine piperidinylamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N- methyl-N-(naphth-l -ylmethyl) propionamide N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S){N'- methanesulfonyl-N'-(naphth- 1 -ylmethyl)aminomethyl } -pyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl }- 2(S)-{N'-acetyl-N'- naphth- 1 -ylmethyl-aminomethyl } -pyrrolidine N-{ 5-(4-Cyanobenzyl)-lH-imidazol-l-yl)acetyl }-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxy]methylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -2(S)- [1(S)-1 -(3- chlorophenyl)- 1 -hydroxy]methylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxy]methylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)methyl } -2(S)- [ 1 (S)- 1 -(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -4(R)-hydroxy-2(S)- [ 1 (R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -4(R)-hydroxy-2(S)- [ 1 (S)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl}-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- IH-imidazol- 1 -ylethyl } -4(R)-hydroxy-2(S)- [ 1 (S)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl]-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- [5-(4-Cyanobenzyl)- IH-imidazol- 1 -ylethylJ-4(R)-hydroxy-2(S)-[ 1 (S)- l-(3-chlorophenyl)-l -hydroxyjmethylpyrrolidine N-[l-(4-Cyanobenzyl)-l-imidazol-5-ylmethylJ-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl } -4(R)-hydroxy-2(S)- { N - acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)-{N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanophenethyl)-lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl-acetyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanopheneth- 1 -yl)- 1 H-imidazol-5-yl-acetyl-4(R)-methoxy- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH~imidazol-5-yl-ethyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl } -2(S)- { N'-acetyl-N'-3- chlorobenzyl-aminomethyljpyrrolidine N-{ l-(4-Cyanophenethyl)-lH~imidazol-5-yl-ethyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl pyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylmethyl }-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl pyrrolidine N-{ l-(4-Cyanobenzyl)-5-imidazolacetyl }-4(R)-benzyloxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-5-imidazol-5-ylmethyl }-4(R)-(2- henylbenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(4- chlorobenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazolemethyl } -4(R)-(4-cyanobenzyloxy)- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazol-5-ylmethyl } -4(R)-(3- pyridylmethoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(ρhenoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(acetyloxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-4(R)-(acetyloxy)-2(S)- { N'-3-chlorobenzyl-N'-acetyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(S)-(phenoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazolethyl } -4(S)-(phenoxy)-2(S)- { N'-acetyl- N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl }-4(S)-fluoro-2(S)-{N * - acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5ylethyl-4(R)-(2-phenylbenzyloxy)- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl }-4(R)-(4- chlorobenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-(4- cyanobenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-(3-pyridylmethoxy)- 2(S)-{N'-acetyl-N'-3-chlorobenzyl}aminomethyl-ρyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl } -2(S)- { N'-acetyl-N'-3- cyanobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S)-{N'-acetyl-N'-3- methoxybenzyl } aminomethylpyrrolidine. N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl } -2(S)- { N'-acetyl-N'-3- trifluoromethylbenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N , -2- methoxybenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl)acetyl } -2(S)- { N'-acetyl-N * -2- trifluoromethylbenzyl } aminomethylpyrrolidine N- { l-(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl }-2(S)- { N"-acetyl-N'-(2,2- diphenylethyl) } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'- diphenylmethyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N , -acetyl-N , -2- chlorobenzyl } aminomethylpyrrolidine N-{2(R)-Methyl-2-(l-(4-Cyanobenzyl)-lH-imidazol-5-yl))acetyl}- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{2(S)-Methyl-2-(l-(4-Cyanobenzyl)-lH-imidazol-5-yl))acetyl}- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N , -acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-4- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N , -2,3- dichlorobenzyl } aminomethylpyrrolidine N-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylJacetyl-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-naphth- 1 -ylmethyl } aminomethylpyrrolidine N- [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylJ acetyl-4(R)-benzyloxy-proline naρhth-1-ylmethylamide N- [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylJacetylproline naphth- 1 - ylmethylamide N- { 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)acetyl-4(R)-methoxy-2(S)- { N'- acetyl-N'-5,6,7,8-tetrahydronaphth- 1 -ylmethyl } aminomethylpyrrolidine N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-5,56,7,8-tetxahydronaphth- 1 -ylmethyl } aminomethyl- pyrrolidine l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl-2(S)-{N'-acetyl-N'-3- chlorobenzy 1 } aminomethylpyrrolidine N-Allyloxycarbonyl-2(S)-{ (l-(4-Cyanobenzyl)-lH-imidazol-5- yl)acetyl}amino-3(S)-methyl-pentanamine 2(S)- { ( 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl } amino-3(S)-methyl- N-(naphth-2-ylsulfonyl)-pentanamine N- Acetyl-N-2-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl)acetyl } amino-3 (S)-methyl-pentanamine N- Acetyl-N-3-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl)acetyl } amino-3(S)-methyl-pentanamine N-Acetyl-N-4-chlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yl)acetyl } amino-3(S)-methyl-pentanamine N-Acetyl-N-2,3-dichlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol- 5-yl)acetyl } amino-3(S)-methyl-pentanamine N- Allyloxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { 2(R,S)-methyl-2-( 1 -(4- cyanobenzyl)-lH-inιidazol-5-yl)acetyl}amino-3(S)-methyl-pentanamine N-t-Butoxycarbonylaminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4- cyanobenzyl)-lH-imidazol-5-ylacetyl}amino-3(S)-methylpentanamine N- Aminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H- imidazol-5-ylacetyl } amino-3 (S)-methylpentanamine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)ethyl }-2(S)- { N'-acetyl-N*-3- chlorobenzyl } aminomethylpyrrolidine N- { 5-(4-Cyanobenzyl)- 1 H-imidazol- 1 -yl)ethoxycarbonyl } -2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -ylacetyl } -2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)ethyl}-2(S)-{N * -acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-{N , -acetyl-N , -3- chlorophenyl } aminomethylpyrrolidine hydrochloride N- { l-(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl }-2(S)- { N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)-ylmethylJ-(N-2- methylbenzyl)glycine N'-(3-chlorophenyl)amide 1 - [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetylJ pyrrolidin-2(S)- ylmethyl]-(N-2-methylbenzyl)-glycine N'-(3-chlorophenylmethyl) amide N-[l-(3-[lH-Imidazol-4-ylJpropionyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)-glycine N'-methyl-N'-(3-chlorophenyl) amide l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetylJ pyrrolidin-2(S)- ylmethylJ-(N-2-methylbenzyl)-glycine N'-methyl-N'-(3- chlorophenylmethyl) amide (S)-2-[(l-(4-cyanobenzyl)-5-imidazolylmethyl)amino]-l-[N-(2,3- dimethylphenyl)acetamido]hexane (S)-2-[iV * -(l-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(methyl)amino]-l- [N-(2,3-dimethylphenyl)acetamido]hexane N-[l-(4-cyanobenzyl)-5-imidazolylmethylJ-N'-(3- chlorophenyl)ethylenediamine l-(4-Cyanobenzyl)-5-[N-(3-phenylpropyl)aminomethylJ imidazole and (S)-2-[(l-(4-Cyanobenzyl)-5-imidazolylmethyl)aminoJ-N- (benzyloxycarbonyl)- -(3-chlorobenzyl)-4-(methanesulfonyl)butanamine or the pharmaceutically acceptable salts thereof. Specific examples of the compounds of the invention are: N-Allyloxycarbonyl-N- l-naphthylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N- 1 - Acetyl-N-naphthylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5- yl)acetyl } amino-3 (S)-methylpentanamine N-Propionyl-N- 1 -naphthylmethyl-2(S)- { ( 1 -(4-cy anobenzyl)- 1 H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Methylsulfonyl-N- 1 -naphthylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Ethylsulfonyl-N- 1 -naphthylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)J acetyl }amino-3- (phenylacetyl)amino- N-methyl-N-benzyl) propionamide N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycine piperidinylamide N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S)-{N'-acetyl-N'- (naphth- 1 -ylmethyl)aminomethyl } -pyrrolidine N-(2,3-Dimethylphenyl)-N-methoxycarbonyl-2(S)-[4-cyanobenzyl-4- (imidazolylmethyl)aminoJ-3(S)-methylpentamine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)ethyl } -2(S)- [ 1 (R)- 1-(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- IH-imidazol- 1 -ylethyl }-4(R)-hydroxy-2(S)-[l (R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl]-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl } -2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine or the pharmaceutically acceptable salts or optical isomers thereof. In the present invention, the amino acids which are disclosed are identified both by conventional 3 letter and single letter abbreviations as indicated below: The compounds of the present invention may have asymmetric centers and occur as racemates, racemic mixtures, and as individual diastereomers, with all possible isomers, including optical isomers, being included in the present invention. It is also understood that when a bond is drawn from a substituent into a ring, such as the bonds drawn into the imidazolyl ring in formula la hereinabove, that attachement of that substituent is at any carbon or heteroatom of the ring as long as a stable compound is formed. As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. As used herein, "cycloalkyl" is intended to include non- aromatic cyclic hydrocarbon groups having the specified number of carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. "Alkenyl" groups include those groups having the specified number of carbon atoms and having one or several double bonds. Examples of alkenyl groups include vinyl, allyl, isopropenyl, pentenyl, hexenyl, heptenyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, 1-propenyl, 2-butenyl, 2-methyl-2-butenyl, isoprenyl, famesyl, geranyl, geranylgeranyl and the like. As used herein, "aryl" is intended to include any stable monocyclic, bicyclic or tricyclic carbon ring(s) of up to 7 members in each ring, wherein at least one ring is aromatic. Examples of aryl groups include phenyl, naphthyl, anthracenyl, biphenyl, tetrahydronaphthyl, indanyl, phenanthrenyl and the like. The term heterocycle or heterocyclic, as used herein, represents a stable 5- to 7-membered monocyclic or stable 8- to 11- membered bicyclic or stable 11-15 membered tricyclic heterocycle ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic elements include, but are not limited to, azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydro- benzothienyl, dihydrobenzothiopyranyl, dihydrobenzothio-pyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, mo holinyl, naphthyridinyl, oxadiazolyl, oxazolyl, isoxazolyl, 2-oxoazepinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, piperidyl, piperazinyl, pyridyl, pyridyl N-oxide, pyridonyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolinyl N-oxide, quinoxalinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydro-quinolinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, and thienyl. As used herein, the terms "substituted aryl", "substituted heterocycle" and "substituted cycloalkyl" are intended to include the cyclic group which is substituted with 1 or 2 substitutents selected from the group which includes but is not limited to F, Cl, Br, CF3, NH2, N(Cι- C6 alkyl)2, Nθ2, CN, (C1-Q5 alkyl)0-, -OH, (C1-C6 alkyl)S(0) m -, (Cl- C6 alkyl)C(0)NH-, H2N-C(NH)-, (C1-C6 alkyl)C(O)-, (C1-C6 alkyl)OC(O)-, N3 C1-C6 alkyl)OC(0)NH- and C1-C2O alkyl. The following structure: represents a cyclic amine moiety having 5 or 6 members in the ring, such a cyclic amine which may be optionally fused to a phenyl or cyclohexyl ring. Examples of such a cyclic amine moiety include, but are not limited to, the following specific structures: It is also understood that substitution on the cyclic amine moiety by Rl3 and Rl3b ma y be on different carbon atoms or on the same carbon atom. When R2 and R3 are combined to form - (CH2)s - > cyclic moieties are formed. Examples of such cyclic moieties include, but are not limited to: The pharmaceutically acceptable salts of the compounds of this invention include the conventional non-toxic salts of the compounds of this invention as formed, e.g., from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like: and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenyl- acetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxy-benzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, trifluoroacetic and the like. It is intended that the definition of any substituent or variable (e.g., RlO, Z, n, etc.) at a particular location in a molecule be independent of its definitions elsewhere in that molecule. Thus, -N(RlO)2 represents -NHH, -NHCH3, -NHC2H5, etc. It is understood that substituents and substitution patterns on the compounds of the instant invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art as well as those methods set forth below. Preferably, Rla and Rib are independently selected from: hydrogen, -N(Rl°)2, R1°C(0)NR1 Π - or unsubstituted or substituted Cl- C6 alkyl wherein the substituent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted phenyl, -N(Rl π )2, R1 Π O- and Rl π C(0)NRl π -. More preferably, Rla and R ib are independently selected from: hydrogen or unsubstituted or substituted C1-C6 alkyl. Further preferably, Rib is not -N(Rl°)2 or C1-C6 alkyl substituted with -N(RlO) 2 . Preferably, R2 and R3 are independently selected from: a side chain of a naturally occurring amino acid, methionine sulfoxide, methionine sulfone, C1-C6 alkyl and C1-C6 alkyl substituted by a group selected from aryl, heterocycle and C3-C10 cycloalkyl; or R2 or R3 are combined with R7 to form a ring such that ■ Most preferably, R2 or R3 are combined with R7 to form a ring such that Preferably, R4 and R5 are independently selected from: H, unsubstituted or substituted C1-C6 alkyl, Rl π O- and halogen. Preferably, Rl3 and R 13b are independently selected from: H, unsubstituted or substituted C1-C6 alkyl, R 4θ- and halogen. Preferably, R6 is not hydrogen or C1-C6 alkyl when A3 is .- N(R7)-. Preferably, R is hydrogen, unsubstituted aryl, substituted aryl, or C1-C6 alkyl substituted with an unsubstituted aryl or a substituted aryl. Most preferably, R7 is substituted aryl or C1-C6 alkyl substituted with a substituted aryl . Preferably, R8 is selected from: hydrogen, perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0)πr, CN, Nθ2, Rlθ2N-C(NRlO)-, Rlθc(θ)-, RlOθC(O)-, N3, -N(RlO)2, or RHOC(O)NR10- and C1-C6 alkyl. Preferably, R9 is hydrogen. Preferably, RlO is selected from H, C1-C6 alkyl and benzyl. Preferably, Al and A2 are independently selected from: a bond, -C(0)NR7-, -NR7C(0)-, O, -N(R7)-, -S(0)2N(R7)- and- Preferably, A4 is selected from a bond and O. Preferably, V is selected from hydrogen, heterocycle and aryl. More preferably, V is phenyl. Preferably, W is selected from imidazolinyl, imidazolyl, oxazolyl, pyrazolyl, pyrrolidinyl, thiazolyl and pyridyl. More preferably, W is selected from imidazolyl and pyridyl. Preferably, Z is O or H2- Most preferably, Z is H2. Preferably, n and p are independently 0, 1, or 2. Preferably r is 1, 2 or 3. Preferably t is 3 or 4. Preferably q is 1. The pharmaceutically acceptable salts of the compounds of this invention can be synthesized from the compounds of this invention which contain a basic moiety by conventional chemical methods. Generally, the salts are prepared by reacting the free base with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid in a suitable solvent or various combinations of solvents. The compounds of the invention can be synthesized from readily available amino acids by conventional peptide synthesis techniques, and the additional methods, well known in the art, described below. Standard methods of peptide synthesis are disclosed, for example, in the following works: Schroeder et al, "The Peptides", Vol. I, Academic Press 1965, or Bodanszky et al, "Peptide Synthesis", Interscience Publishers, 1966, or McOmie (ed.) "Protective Groups in Organic Chemistry", Plenum Press, 1973, or Barany et al, "The Peptides: Analysis, Synthesis, Biology" 2, Chapter 1, Academic Press, 1980, or Stewart et al., "Solid Phase Peptide Synthesis", Second Edition, Pierce Chemical Company, 1984. Also useful in exemplifying syntheses of specific unnatural amino acid residues are European Pat. Appl. No. 0 350 163 A2 (particularly page 51-52) and J. E. Baldwin et al Tetrahedron, 50:5049-5066 (1994). The teachings of these works are hereby incorporated by reference. Abbreviations used in the description of the chemistry and in the Examples that follow are: Compounds of this invention are prepared by employing the reactions shown in the following Reaction Schemes A-J, in addition to other standard manipulations such as ester hydrolysis, cleavage of protecting groups, etc., as may be known in the literature or exemplified in the experimental procedures. Some key bond-forming and peptide modifying reactions are: Reaction A Amide bond formation and protecting group cleavage using standard solution or solid phase methodologies. Reaction B Preparation of a reduced peptide subunit by reductive alkylation of an amine by an aldehyde using sodium cyanoborohydride or other reducing agents. Reaction C Alkylation of a reduced peptide subunit with an alkyl or aralkyl halide or, alternatively, reductive alkylation of a reduced peptide subunit with an aldehyde using sodium cyanoborohydride or other reducing agents. Reaction D Peptide bond formation and protecting group cleavage using standard solution or solid phase methodologies. Reaction E Preparation of a reduced subunit by borane reduction of the amide moiety. These reactions may be employed in a linear sequence to provide the compounds of the invention or they may be used to synthesize fragments which are subsequently joined by the alkylation reactions described in the Reaction Schemes and in Reaction Schemes 1- 5 hereinbelow. REACTION SCHEME A Reaction A. Coupling of residues to form an amide bond REACTION SCHEME B Reaction B. Preparation of reduced peptide subunits by reductive alkylation NaCNBH 3 REACTION SCHEME C Reaction C. Alkylation/reductive alkylation of reduced peptide subunits R y CH, NaCNBH 3 REACTION SCHEME D Reaction D. Coupling of residues to form an amide bond R A H 2 N- NRCRD o REACTION SCHEME E Reaction E. Preparation of reduced dipeptides from peptides where RA and RB are R2, R3 or R5 as previously defined; RC and Ji are R7 or Rl2; XL is a leaving group, e.g., Br-, I- or MsO-; and Ry is defined such that R7 is generated by the reductive alkylation process. In addition to the reactions described in Reaction Schemes A - E, other reactions used to generate the compounds of this invention are shown in the Reaction Schemes 1-20. All of the substituents shown in the Reaction Schemes, represent the same substituents as defined hereinabove. The substituent "Ar" in the Reaction Schemes represents a carbocyclic or heterocyclic, substituted or unsubstituted aromatic ring. These reactions may be employed in a linear sequence to provide the compounds of the invention or they may be used to synthesize fragments which are subsequently joined by the alkylation reactions described in the Reaction Schemes. The sequential order whereby substituents are incorporated into the compounds is often not critical and thus the order of reactions described in the Reaction Schemes are illustrative only and are not limiting. Synopsis of Reaction Schemes 1-20: The requisite intermediates are in some cases commercially available, or can be readily prepared according to known literature procedures, including those described in Reaction Schemes A-E hereinabove. Thus, the intermediate II, generally prepared from the appropriate amino acid by the above noted methods with the suitable substituents fully incorporated, (Scheme 3), can be reductively alkylated with a variety of aldehydes, such as III. The aldehydes can be prepared by standard procedures, such as that described by O. P. Goel, U. Krolls, M. Stier and S. Kesten in Organic Syntheses. 1988, 67, 69-75. The reductive alkylation can be accomplished at pH 5-7 with a variety of reducing agents, such as sodium triacetoxyborohydride or sodium cyanoborohydride in a solvent such as dichloroethane, methanol or dimethylformamide. The product IV can be deprotected to give the compounds V with trifluoroacetic acid in methylene chloride. The intermediate V is isolated in the salt form, for example, as a trifluoroacetate, hydrochloride or acetate salt, among others. The product diamine V can further be selectively protected to obtain VI, which can subsequently be reductively alkylated with a second aldehyde to obtain VII. Removal of the protecting group, and conversion to cyclized products such as the dihydroimidazole VIII can be accomplished by literature procedures. Alternatively, the protected intermediate II can be reductively alkylated with other aldehydes (which may be suitably protected if necessary), many of which are readily commercially available, such as 4-bromo-2-thiophenecarboxaldehyde, 5- methoxyindole-3-carboxaldehyde, 6-methyl-2-pyridinecarboxaldehyde, 3-pyridinecarboxaldehyde, 4-imidazolyl-acetaldehyde and the like, to give products such as IX (Reaction Scheme 2). The trityl protecting group can be removed from IX to give X, or alternatively, IX can first be treated with an alkyl halide then subsequently deprotected to give the alkylated imidazole XI. As shown in Reaction Scheme 3, related carboxylic acids, such as the imidazole acetic acid XII, can be converted to the acetate XIII by standard procedures and incorporation of a protecting group, and XIII can be first reacted with an alkyl halide, then treated with refluxing methanol to provide the regiospecifically alkylated imidazole acetic acid ester XIV. Hydrolysis and reaction with the fully functionalized peptidyl portion of the molecule II in the presence of condensing reagents such as l-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) leads to acylated products such as XVI. It is also understood that the reactions illustrated in Reaction Schemes 1-3 can be utilized to prepare an intermediate that can subsequently be treated as described in Reaction Schemes A-E. Thus, as shown in Reaction Schemes 4 and 5, suitably protected amino acids XVII and XVIII, can be reacted with the acetic acid XV to provide intermediates XIX and XX, which can then undergo further functionalization by standard techniques. Reaction Schemes 6 and 7 illustrate synthetic routes to the instant compounds in which the sequential order that the substituents are incorporated is shuffled. Thus in Reaction Scheme 6 the suitably protected aldehyde XXI can be reductively aminated to provide compound XXII. The amine group of XXII can be blocked and the BOC protecting group removed. Coupling with the substituted acetic acid provides XXIV, which can then be deblocked with Pd(PPh3)4 and further functionalized. Alternatively, compound XXII can first be functionalized on the amine to provide, for example, amide XXV. Deprotection and reaction with intermediate XV as before provides the instant compound XXVI. In Reaction Scheme 7, the primary amine XXVIII is prepared from the alcohol XXVII and blocked with an allyloxycarbonyl group. Deprotection and reaction with intermediate XV as before provides the blocked amine XXIX which, after removal of the allyloxycarbonyl protecting moiety by standard procedures, may be mono- or di-substituted using techniques described above. Reaction Scheme 8 illustrates incorporation of a cyclic amine moiety, such as a reduced prolyl moiety, into the compounds of the instant invention. Reduction of the azide XXX provides the amine XXXI, which may be mono- or di-substituted using techniques described above. As an example, incorporation of a naphthylmethyl group and an acetyl group is illustrated. As shown in Reaction Scheme 9, direct attachment of a aromatic ring to a substituted amine such as XXXII is accomplished by coupling with a triarylbismuth reagent, such as tris(3- chlorophenyl)bismuth. Reaction Scheme 10 illustrates the use of protecting groups to prepare compounds of the instant invention wherein the cyclic amine contains an alkoxy moiety. The hydroxy moiety of key intermediate XXXIV may be further converted to a fluoro or phenoxy moiety, as shown in Reaction Scheme 11. Intermediates XXXV and XXXVI may then be further elaborated to provide the instant compounds. compounds wherein the variable -(CR42)qA3(CR*52)nR^ is a suitably substituted -hydroxybenzyl moiety. Thus the protected intermediate aldehyde XXXVII is treated with a suitably substituted phenyl Grignard reagent to provide the enantiomeric mixture XXXVIII. Treatment of the mixture with 2-picolinyl chloride allows chromatographic resolution of compounds IXL and XL. Removal of the picolinoyl group followed by deprotection provides the optically pure intermediate XLI which can be futher processed as described hereinabove to yield the instant compounds. Syntheses of imidazole-containing intermediates useful in synthesis of instant compounds wherein the variable p is 0 or 1 and Z is H2 are shown in Reaction Scheme 13 and 14. Thus the mesylate XLII can be utilized to alkylate a suitably substituted amine or cyclic amine, while aldehyde XLIII can be used to similarly reductively alkylate such an amine. Reaction Scheme 15 illustrates te syntheses of imidazole- containing intermediates wherein the attachment point of the -(CRlb2)p-C(Z)- moiety to W (imidazolyl) is through a ring nitrogen. Reaction Scheme 16 illustrates the synthesis of an intermediate wherein a Rib substitutent is a methyl. Reaction Schemes 17-20 illustrate syntheses of suitably substituted aldehydes useful in the syntheses of the instant compounds wherein the variable W is present as a pyridyl moiety. Similar synthetic strategies for preparing alkanols that incorporate other heterocyclic moieties for variable W are also well known in the art. REACTION SCHEME 1 BocHN IV V VI REACTION SCHEME 1 (continued CF 3 C ° H » CH 2 CI 2 ; NaHCO 3 REACTION SCHEME 2 3 CN H 2 CI 2 XI REACTION SCHEME 3 XII XIII XV REACTION SCHEME 3 (continued) REACTION SCHEME 4 wherein Prot = carboxylic acid protecting group REACTION SCHEME 5 XVIII HOOBT DMF REACTION SCHEME 6 R e REACTION SCHEME 7 REACTION SCHEME 7 (continued) alkylation, acylation or sulfonylation XXIXa REACTION SCHEME 8 REACTION SCHEME 8 (continued) REACTION SCHEME 9 R REACTION SCHEME 10 REACTION SCHEME 10 (continued) n REACTION SCHEME 11 REACTION SCHEME 12 XXXVII OTBS 2-Picolinoyl Chloride XXXVIII REACTION SCHEME 12 (continued) OTBS XLI OH REACTION SCHEME 13 XLII REACTION SCHEME 14 AcoO pyridine Tr XLIII REACTION SCHEME 15 TfOCH 2 C0 2 CH 3 Tr HO XLIV XLV REACTION SCHEME 16 XLVI REACTION SCHEME 17 Zn CI 2l NiCI 2 (Ph 3 P) 2 NaBH 4 (excess) REACTION SCHEME 18 REACTION SCHEME 19 NaBH 4 (excess) REACTION SCHEME 20 excess NaBH 4 The instant compounds are useful as pharmaceutical agents for mammals, especially for humans. These compounds may be administered to patients for use in the treatment of cancer. Examples of the type of cancer which may be treated with the compounds of this invention include, but are not limited to, colorectal carcinoma, exocrine pancreatic carcinoma, myeloid leukemias and neurological tumors. Such tumors may arise by mutations in the ras genes themselves, mutations in the proteins that can regulate Ras activity (i.e., neurofibromin (NF-1), neu, ser, abl, lck, fyn) or by other mechanisms. The compounds of the instant invention inhibit famesyl- protein transferase and the farnesylation of the oncogene protein Ras. The instant compounds may also inhibit tumor angiogenesis, thereby affecting the growth of tumors (J. Rak et al. Cancer Research, 55:4575- 4580 (1995)). Such anti-angiogenesis properties of the instant compounds may also be useful in the treatment of certain forms of blindness related to retinal vascularization. The compounds of this invention are also useful for inhibiting other proliferative diseases, both benign and malignant, wherein Ras proteins are aberrantly activated as a result of oncogenic mutation in other genes (i.e., the Ras gene itself is not activated by mutation to an oncogenic form) with said inhibition being accomplished by the administration of an effective amount of the compounds of the invention to a mammal in need of such treatment. For example, a component of NF-1 is a benign proliferative disorder. The instant compounds may also be useful in the treatment of certain viral infections, in particular in the treatment of hepatitis delta and related viruses (J.S. Glenn et al. Science, 256:1331-1333 (1992). The compounds of the instant invention are also useful in the prevention of restenosis after percutaneous transluminal coronary angioplasty by inhibiting neointimal formation (C. Indolfi et al. Nature medicine, 1:541-545(1995). The instant compounds may also be useful in the treatment and prevention of polycystic kidney disease (D.L. Schaffner et al. American Journal of Pathology, 142: 1051-1060 (1993) and B. Cowley, Jr. et al.FASEB Journal, 2: A3160 (1988)). The instant compounds may also be useful for the treatment of fungal infections. The compounds of this invention may be administered to mammals, preferably humans, either alone or, preferably, in combination with pharmaceutically acceptable carriers or diluents, optionally with known adjuvants, such as alum, in a pharmaceutical composition, according to standard pharmaceutical practice. The compounds can be administered orally or parenterally, including the intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical routes of administration. For oral use of a chemotherapeutic compound according to this invention, the selected compound may be administered, for example, in the form of tablets or capsules, or as an aqueous solution or suspension. In the case of tablets for oral use, carriers which are commonly used include lactose and corn starch, and lubricating agents, such as magnesium stearate, are commonly added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous use, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled in order to render the preparation isotonic. The present invention also encompasses a pharmaceutical composition useful in the treatment of cancer, comprising the administration of a therapeutically effective amount of the compounds of this invention, with or without pharmaceutically acceptable carriers or diluents. Suitable compositions of this invention include aqueous solutions comprising compounds of this invention and pharmacologically acceptable carriers, e.g., saline, at a pH level, e.g., 7.4. The solutions may be introduced into a patient's intramuscular blood-stream by local bolus injection. The compounds of the instant invention may also be co- administered with other well known therapeutic agents that are selected for their particular usefulness against the condition that is being treated. For example, the instant compounds may be useful in combination with known anti-cancer and cytotoxic agents. Similarly, the instant compounds may be useful in combination with agents that are effective in the treatment and prevention of NF- 1 , restenosis, polycystic kidney disease, infections of hepatitis delta and related viruses and fungal infections. If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described below and the other pharmaceutically active agent(s) within its approved dosage range. Compounds of the instant invention may alternatively be used sequentially with known pharmaceutically acceptable agent(s) when a combination formulation is inappropriate. When a compound according to this invention is administered into a human subject, the daily dosage will normally be determined by the prescribing physician with the dosage generally varying according to the age, weight, and response of the individual patient, as well as the severity of the patient's symptoms. In one exemplary application, a suitable amount of compound is administered to a mammal undergoing treatment for cancer. Administration occurs in an amount between about 0.1 mg/kg of body weight to about 20 mg/kg of body weight per day, preferably of between 0.5 mg/kg of body weight to about 10 mg/kg of body weight per day. The compounds of the instant invention are also useful as a component in an assay to rapidly determine the presence and quantity of famesyl-protein transferase (FPTase) in a composition. Thus the composition to be tested may be divided and the two portions contacted with mixtures which comprise a known substrate of FPTase (for example a tetrapeptide having a cysteine at the amine terminus) and famesyl pyrophosphate and, in one of the mixtures, a compound of the instant invention. After the assay mixtures are incubated for an sufficient period of time, well known in the art, to allow the FPTase to farnesylate the substrate, the chemical content of the assay mixtures may be determined by well known immunological, radiochemical or chromatographic techniques. Because the compounds of the instant invention are selective inhibitors of FPTase, absence or quantitative reduction of the amount of substrate in the assay mixture without the compound of the instant invention relative to the presence of the unchanged substrate in the assay containing the instant compound is indicative of the presence of FPTase in the composition to be tested. It would be readily apparent to one of ordinary skill in the art that such an assay as described above would be useful in identifying tissue samples which contain famesyl-protein transferase and quantitating the enzyme. Thus, potent inhibitor compounds of the instant invention may be used in an active site titration assay to determine the quantity of enzyme in the sample. A series of samples composed of aliquots of a tissue extract containing an unknown amount of famesyl-protein transferase, an excess amount of a known substrate of FPTase (for example a tetrapeptide having a cysteine at the amine terminus) and famesyl pyrophosphate are incubated for an appropriate period of time in the presence of varying concentrations of a compound of the instant invention. The concentration of a sufficiently potent inhibitor (i.e., one that has a Ki substantially smaller than the concentration of enzyme in the assay vessel) required to inhibit the enzymatic activity of the sample by 50% is approximately equal to half of the concentration of the enzyme in that particular sample. EXAMPLES Examples provided are intended to assist in a further understanding of the invention. Particular materials employed, species and conditions are intended to be further illustrative of the invention and not limitative of the reasonable scope thereof. EXAMPLE 1 N- Allyloxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H- imidazol-5-y1)acetyl lamino-3(S)- methylpentanamine Step A: Preparation of lH-Imidazole-4- acetic acid methyl ester hydrochloride. A solution of lH-imidazole-4-acetic acid hydrochloride (4.00g, 24.6 mmol) in methanol (100 ml) was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature (RT) for 18hr. The solvent was evaporated in vacuo to afford the title compound as a white solid. lH NMR(CDCl3, 400 MHz) δ 8.85(1H, s),7.45(lH, s), 3.89(2H, s) and 3.75(3H, s) ppm. Step B: Preparation of l-(Triphenylmethyl)-lH-imidazol-4-ylacetic acid methyl ester. To a solution of the product from Step A (24.85g, 0.141mol) in dimethyl formamide (DMF) (115ml) was added triethylamine (57.2 ml, 0.412mol) and triphenylmethyl bromide(55.3g, 0.171mol) and the suspension was stirred for 24hr. After this time, the reaction mixture was diluted with ethyl acetate (EtOAc) (1 1) and water (350 ml). The organic phase was washed with sat. aq. NaHC03 (350 ml), dried (Na2Sθ4) and evaporated in vacuo. The residue was purified by flash chromatography (Siθ2, 0-100% ethyl acetate in hexanes; gradient elution) to provide the title compound as a white solid. lH NMR (CDC13, 400 MHz) δ 7.35(1H, s), 7.31(9H, m), 7.22(6H, m), 6.76QH, s), 3.68(3H, s) and 3.60(2H, s) ppm. Step C: Preparation of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid methyl ester. To a solution of the product from Step B (8.00g, 20.9mmol) in acetonitrile (70 ml) was added bromo-p-tolunitrile (4.10g, 20.92 mmol) and heated at 55°C for 3 hr. After this time, the reaction was cooled to room temperature and the resulting imidazolium salt (white precipitate) was collected by filtration. The filtrate was heated at 55 °C for 18hr. The reaction mixture was cooled to room temperature and evaporated in vacuo. To the residue was added EtOAc (70 ml) and the resulting white precipitate collected by filtration. The precipitated imidazolium salts were combined, suspended in methanol (100 ml) and heated to reflux for 30min. After this time, the solvent was removed in vacuo, the resulting residue was suspended in EtOAc (75ml) and the solid isolated by filtration and washed (EtOAc). The solid was treated with sat aq NaHC03 (300ml) and CH2CI2 (300ml) and stirred at room temperature for 2 hr. The organic layer was separated, dried (MgS04) and evaporated in vacuo to afford the title compound as a white solid : lHNMR(CDCl3, 400 MHz) δ 7.65(1H, d, J=8Hz), 7.53(1H, s), 7.15(1H, d, J=8Hz), 7.04(1H, s), 5.24(2H, s), 3.62(3H, s) and 3.45(2H, s) ppm. Step D: Preparation of [l-(4-cyanobenzyl)-lH-imidazol-5-yllacetic acid. A solution of [l-(4-cyanobenzyl)-lH-imidazol-5-yl] acetic acid methyl ester (4.44g, 17.4mmol ) in THF (100ml) and 1 M lithium hydoxide (17.4 ml, 17.4 mmol) was stirred at RT for 18 hr. 1 M HCl (17.4 ml) was added and the THF was removed by evaporation in vacuo. The aqueous solution was lyophilised to afford the title compound containing lithium chloride as a white solid. lH NMR(CD3θD, 400 MHz) δ 8.22(1H, s), 7.74(1H, d, J=8.4Hz), 7.36(1H, d, J=8.4Hz), 7.15(1H, s), 5.43(2H, s) and 3.49(2H, s) ppm. Step E: Preparation of N-Naphth-l-ylmethyl-2(S)-(t-butoxy- carbonyl)amino-3(S)-methylpentanamine To a slurry of 1-naphthylmethylamine (5.84g, 37.2 mmol), crushed 3A molecular sieves (lOg), and N-t-butoxycarbonyl-isoleucinal (8.0g, 37.2 mmol) in 1,2-dichloroethane (50 ml) was added sodium triacetoxyborohydride (15.8g, 74.3 mmol) at 0°C. The reaction was allowed to warm slowly to RT and stirred for 48 hrs. The reaction was cooled to 0°C and quenched with sat. aq. NaHC03 and stirred for 30min. The organic layer was separated, washed with saturated brine, dried (MgSθ4) and evaporated in vacuo. The residue was purified by flash chromatography (Siθ2, 25% ethyl acetate in hexanes) to provide the title compound as an oil. lHNMR(CDCl3, 400 MHz) δ 8.16(1H, d, J=7.9Hz), 7.87(1H, d, J=7.9Hz), 7.78(1H, d, J=7.7Hz), 7.60-7.40 (4H, m), 4.62(1H, m), 4.25(1H, d, J=13.2Hz), 4.19QH, d, J=13.2Hz), 3.68(1H, m), 2.90- 2.70(2H, m), 1.70-1.35(3H, m) and 1.45(9H, s) 1.12(1H, m) and 1.00- 0.80 (6H, m) ppm. Step F: Preparation of N-Allyoxycarbonyl-N-naphth-1-ylmethyl- 2(S)-(t-butoxycarbonyl)amino-3(S)-methylpentanamine To a solution of the amine from step E (4.62g, 13.0 mmol), and triethylamine (4.40ml, 31.6 mmol) at 0°C , allylchloroformate (1.85ml, 17.4 mmol) was added dropwise. The reaction was allowed to warm slowly to RT and stirring was continued for 18hrs. The solvent was evaporated in vacuo and the residue was chromatographed (Siθ2, 10% EtOAc in hexanes) to afford the title compound as an oil. lHNMR(CDCl3, 400 MHz) δ 8.10(0.4H, d, J=7.9Hz), 8.00(0.6H, d, J=7.9Hz), 7.88(1H, m), 7.80(1H, m), 7.60-7.30 (4H, m), 6.10-5.85(1H, m), 5.50-5.10(3H, m), 4.90-4.40(4H,m), 3.90(lH,m), 3.71(0.6H, t, J= 12.6Hz), 3.36(0.4H,t, J= 12.6Hz), 2.90-2.70(lH,m), 1.47(9H,s), 1.50- 1.20(2H,m), 1.05(lH,m)and 0.95-0.70 (6H, m) ppm. FAB HRMS exact mass calc'd for C26H37N2O4 441.275333 (MH+), found 441.275084. Step G: Preparation of N-Allyoxycarbonyl-N-naphtJi-l-ylmethyl- 2(S)-amino-3(S)-methylpentanamine hydrochloride A solution of the product from step F (4.75g, 10.8 mmol) in EtOAc (200 ml) at 0°C was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature (RT) for 30min. The solvent was evaporated in vacuo to afford the title compound as a white solid. !H NMR(CD3θD, 400 MHz) δ 8.06(1H, m), 7.93(1H, m), 7.88(lH,d, J=8.2Hz), 7.60-7.45(3H,m), 7.38(lH,m), 6.01(lH,m), 5.40-5.19(2H,m), 5.10(2H,m), 4.80-4.60(2H,m), 3.62(lH,m), 3.50-3.20(lH,m), 3.11(lH,m), 1.57(lH,m), 1.23(lH,m), 1.03(lH,m) and 0.90-0.75(6H,m) ppm. FAB HRMS exact mass calc'd for C21H29N2O2 341.222903 (MH+), found 341.223321 Step H: Preparation of N-Allyoxycarbonyl-N-naphth-1-ylmethyl- 2(S)-[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino- 3(S)-methylpentanamine hydrochloride To a solution of the acid from step D (1.47g, 3.32mmol), the amine hydrochloride salt from step G (1.252g, 3.32mmol), HOOBT (650mg, 3.98mmol), and triethylamine (1.60ml, llmmol) in DMF was added EDC (764mg, 3.99 mmol). The reaction was stirred at room temperature for 48hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3 , brine , dried (Na2Sθ4). and evaporated in vacuo. The residue was chromatographed (Siθ2, 3.5% MeOH in CH2CI2) to afford the title compound as an oil. lH NMR(CD3θD, 400 MHz) δ 8.00-7.70 (6H, m), 7.52(2H, m), 7.44(lH,t, J=7.6Hz), 7.38-7.25(3H,m), 6.96(lH,s), 6.10-5.90(lH,m), 5.43(2H,m), 5.40-4.80(5H,m), 4.60(2H,m), 4.18(lH,m), 3.60- 3.10(4H,m), 1.40(2H,m), 1.06(lH,m), 0.85(3H, t, J=7.5Hz), and 0.77(3H, d, J=7.5Hz) ppm. Anal, calc'd for C34H37N5O3 0.65H2O: C, 70.97; H, 6.71; N, 12.17. Found: C, 70.59; H, 6.59; N, 12.56. FAB HRMS exact mass calc'd for C34H38N5O3 564.297465(MH+), found 564.296221 EXAMPLE 2 N-Naphth-l-ylme l-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yl)acetyliamino-3(S)- methyl pentanamine The product of Example 1 (1.67g, 2.96 mmol), and 5,5- dimethyl-1,3- cyclohexandione (3.31g, 23.6 mmol) were combined, the flask was purged with argon and tetrakis(triphenylphosphine) palladium (0) (585mg, 0.506 mmol) was added and the flask purged with argon again. The flask was wrapped with foil , THF (36ml) was added and the reaction was stirred in the dark, at room temperature for 90min. The solvent was evaporated in vacuo and the residue was chromatographed (Siθ2, 2% NH4OH in 98% CH3CN -5% NH4OH in 95% CH3CN and then 5% MeOH,5% NH4OH in 90% CH3CN; gradient elution) to afford the title compound as a pale yellow solid. !H NMR(CD3θD, 400 MHz) δ 8.10(1H, m),7.98(lH,m), 7.84(lH,d, J=7.5Hz), 7.68(lH,s), 7.63(2H, d, J=8.3Hz), 7.53(2H,m), 7.48-7.40(2H, m), 7.16(2H,d, J=8.3Hz), 6.91(1H, s), 5.30(2H, s), 4.35(1H, d, J=13.3Hz), 4.22(1H, d, J=13.3Hz), 3.96(1H, m), 3.40(1H, dd, J=15.7 and 7.0Hz), 3.36-3.28(lH,m), 2.96(1H, dd, J=11.9 and 3.6Hz), 2.75(1H, dd, J=11.9 and 9.5Hz), 1.60-1.35(2H,m), 1.20-1.05(lH,m), 0.95-0.84(6H,m) ppm. Anal, calc'd for C30H33N5O1 0.25H2O: C, 74.43; H, 6.97; N, 14.47. Found: C, 74.39; H, 6.92; N, 14.34. FAB HRMS exact mass calc'd for C30H34N5O1 480.276336 (MH+), found 480.276866 EXAMPLE 3 N-Methoxycarbonyl-N-naphth- l-ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl)amino-3(S)- methyl pentanamine. To a solution of the product of Example 2 (40mg, 0.083 mmol) in CH2CI2 (1ml) and triethylamine (24μl, 0.17mmol) at 0°C was added methyl chloroformate(39μl of a 2.1M solution in CH2CI2, 0.082 mmol). The reaction was stirred at room temperature for 3hr, the solvent evaporated in vacuo and the residue purified by preparative HPLC (C-18; 95:5 to 5:95 water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution). Lyophilisation of the collected fractions afforded the title compound as a white solid. lH NMR(CD30D, 400 MHz) δ 8.97(1H, m), 8.02-7.76(5H, m), 7.80- 7.20(7H,m), 5.58(2H,s), 5.12( lH,m), 4.20(lH,m), 3.80-3.45(6H,m), 3.16(lH,m), 1.42(2H,m), 1.08QH, m), 0.90-0.80(3H,m), and 0.77(3H, d, J=7.0Hz) ppm. FAB Mass spectmm, m/z = 538 (M+l). Anal, calc'd for C32H35N5O3 0.25H2O, 1.85TFA; C, 56.94; H, 5.00; N, 9.30. Found: C, 56.96; H, 5.02; N, 9.26. EXAMPLE 4 N- Acetyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol- 5-yl)acetyl}amino-3(S)-methylpentanamine. The title compound was prepared using the protocol described in Example 3 using acetyl chloride in place of methylchloroformate. lH NMR(CD30D, 400 MHz) δ 8.98(1H, m),8.20-7.76(6H, m), 7.70- 7.20(7H, m), 5.70-5.40(2H, m), 5.09(1H, m), 4.80-4.60(0.5H, m), 4.28(0.5H, m), 4.14(0.5H, m), 3,75(1H, m), 3.65-3.60(1.5H,m), 3.40- 3.10(2H,m), 2.22(1.5H, s), 2.02(1.5H, s), 1.45(2H,m), 1.11(1H, m), 0.87(3H, t, J=7.0Hz), 0.81(1.5H, d, J=7.0Hz), 0.75(1.5H, d, J=7.0Hz) ppm. FAB Mass spectrum, m/z = 522 (M+ 1 ). Anal, calc'd for C32H35N5O2 0.05H20, 2.35TFA; C, 55.76; H, 4.78; N, 8.86. Found: C, 55.77; H, 4.78; N, 8.94. EXAMPLE 5 N-Propionyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1H- imidazol-5-yl)acetyl } amino-3(S)- methylpentanamine. The title compound was prepared using the protocol described in Example 3 using propionyl chloride in place of methylchloroformate. lH NMR(CD3θD, 400 MHz) δ 8.90(1H, m), 8.20-7.76(6H, m), 7.70- 7.16(7H, m), 5.70-5.40(2H, m), 5.09(1H, m), 4.80-4.60(0.5H, m), 4.27(0.5H, m), 4.14(0.5H, m), 3,82-3.64(lH, m), 3.65-3.60(1.5H,m), 3.42-3.05(lH,m), 2.64-2.20(2H,m), 1.45(2H,m), 1.15(1.5H, t, J=7.2Hz), 1.20-1.10(lH,m), 1.03(1.5H, t, J=7.2Hz), 0.96-0.70((6H,m) ppm. FAB Mass spectram, m/z = 536 (M+l). Anal, calc'd for C32H35N5O2 0.05H2O, 1.80TFA; C, 59.26; H, 5.29 N, 9.44. Found: C, 59.26; H, 5.29; N, 9.39. EXAMPLE 6 N-Methylsulfonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl )amino-3(S)- methylpentanamine. The title compound was prepared using the protocol described in Example 3 using methane sulfonyl chloride in place of methylchloroformate. lH NMR(CD30D, 400 MHz) δ 8.97(1H, m),8.30(lH,m), 7.95-7.90(2H, m), 7.81(2H, d, J=8.2Hz), 7.60-7.35(8H, m), 5.52(2H, s), 5.02(lH,d, J=14.4Hz), 4.74(lH,d, J=14.4Hz), 3.56-3.30(4H, m), 3.18(lH,dd, J=14.6Hz and 3Hz), 2.98(3H,s), 1.26(1H, m), 1.16(lH,m), 0.92(lH,m), 0.69(3H, t, J=7.1Hz) and 0.61(3H,d, J=7.1Hz) ppm. FAB Mass spectrum, m/z = 558 (M+l). Anal, calc'd for C31H35N5O3S , 1.90TFA; C, 53.98; H, 4.80 N, 9.04. Found: C, 53.96; H, 4.81; N, 9.07. EXAMPLE 7 N-Ethylsulfonyl-N-naphth- l-ylmethyl-2(S)- { ( 1 -(4-cy anobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine. The title compound was prepared using the protocol described in Example 3 using ethane sulfonyl chloride in place of methylchloroformate. lH NMR(CD3θD, 400 MHz) δ 8.97(1H, m),8.27(lH,m), 7.92(2H, m), 7.81(2H, d, J=8.2Hz), 7.60-7.35(8H, m), 5.55(2H, s), 5.02(lH,d, J=14.4Hz), 4.76(lH,d, J=14.4Hz), 3.60-3.35(4H, m), 3.18(lH,dd, J=14.6Hz and 3Hz), 3.10(2H,m), 1.63(3H,t, J=6.5Hz), 1.30-1.10(2H, m), 0.94(lH,m), 0.71(3H, t, J=7.1Hz) and 0.61(3H,d, J=7.1Hz) ppm. FAB Mass spectrum, m/z = 572 (M+l). Anal, calc'd for C32H37N5O3S , 0.15 H2O, 1.40TFA; C, 56.94; H, 5.3 IN, 9.54. Found: C, 56.97; H, 5.32; N, 9.54. EXAMPLE 8 N-Methylaminocarbonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4- cvanobenzyl ) -lH-imidazol-5-yl ) acetyllamino-3(S)- methylpentanamine. To a solution of the amine from Example 2 (40mg, 0.083 mmol) in CH2CI2 (1ml) at 0°C was added methyl isocyanate (20μl of a 4.24M solution in CH2C12)- The reaction was stirred at room temperature for 2hr, the solvent evaporated in vacuo and the residue purified by preparative HPLC ( C-18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution). Lyophilisation of the collected fractions afforded the trifluoroacetate salt of the title compound as a white solid. iH NMR(CD30D, 400 MHz) δ 8.97(1H, m),8.00-7.76(6H, m), 7.60- 7.40(6H,m), 7.28(lH,d, J=7.4Hz), 5.58(2H, s), 5.05(lH,m), 4.90- 4.70(2H,m), 4.30-4.05(lH,m), 3.75-3.45(3H,m), 3.12(1H, dd, J=15.6 and 4.2 Hz), 2.73(3H,s), 1.50-1.35(2H,m), 1.12-1.09(lH,m), 0.90-0.8 l(3H,m) and 0.78(3H,d, J=6.7Hz) ppm. FAB Mass spectmm, m z = 537 (M+l). Anal, calc'd for C32H36N6O2 0.15H2O, 1.60TFA; C, 58.57 H, 5.29 N, 11.64. Found: C, 58.56; H, 5.28; N, 11.66. EXAMPLE 9 N-Propyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol- 5-yl)acetyl lamino-3(S)- methylpentanamine To a slurry of the amine prepared in Example 2 (100.6mg, 0.21 mmol), cmshed 3 A molecular sieves (290mg), and propionaldehyde (15.5ml, 0.22 mmol) in 1,2 dichloroethane (2 ml) was added sodium triacetoxyborohydride (53.6mg, 0.253 mmol) at 0°C. The reaction was allowed to warm slowly to RT and stirred for 48 hrs. The reaction was cooled to 0°C diluted with EtOAc and quenched with sat. aq. NaHC03 and stirred for 30min. The organic layer was separated, washed with saturated brine, dried( MgS04) and purified by preparative HPLC ( C-18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution). Lyophilisation of the collected fractions afforded the trifluroacetate salt of the title compound as a white solid. A portion of the product was partitioned between EtOAc and sat aq. Na2C03, the organic layer separated and dried (Na2S04) and the solvent evaporated in vacuo to afford the corresponding free base as an oil. lH NMR Free Base (CD3OD, 400 MHz) δ 8.30(1H, d, J=7.5Hz), 7.83(1H, d, J=7.5Hz), 7.77(1H, d, J=7.5Hz), 7.70-7.60(3H,m), 7.50- 7.30(4H,m), 7.15(2H, d, J=8.7Hz), 6.85(1H, s), 5.30(2H,s), 4.02- 3.90(3H,m), 3.23(2H,m), 2.56(1H, dd, J=12.4 and 5.8Hz), 2.44(2H, t, J=7.4Hz), 2.36(1H, dd, J=12.4 and 8.9Hz), 1.56(2H,m), 1.45(lH,m), 1.07(lH,m), 0.90-0.76(lH,m), 0.83(3H,t, J=7.6Hz), 0.73(3H,d, J=7.6Hz) and 0.64(3H,t, J=7.6Hz) ppm. FAB Mass spectmm, m/z = 522 (M+l). Anal, calc'd for C32H39N5O 0.15H20, 2.70TFA; C, 58.57 H, 5.29 N, 11.64. Found: C, 58.56; H, 5.28; N, 11.66. EXAMPLE 10 N-3-Chlorobenzyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl )amino-3(S)- methylpentanamine To a slurry of the amine prepared in Example 2 (45.0mg, 0.094 mmol), crushed 3A molecular sieves (190mg), and 3- chlorobenzaldehyde (13μl, 0.11 mmol) in methanol (2 ml) was added sodium cyanoborohydride (125μl of a IM solution in THF, 0.13 mmol) at room temperature The reaction was stirred at RT for 18 hrs, and 3- chlorobenzaldehyde (26μl, 0.22 mmol) and sodium cyanoborohydride (200μl of a IM solution in THF, 0.20 mmol) was added. The reaction was stirred an additional 18hr and then diluted withEtOAc, quenched with sat. aq. NaHC03 and stirred for 30min. The organic layer was separated, washed with saturated brine, dried( Na2S04) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC ( C- 18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution). Lyophilisation of the collected fractions afforded the trifluroacetate salt of the title compound as a white solid. A portion of the product was partitioned between EtOAc and sat aq. Na2C03, the organic layer separated, dried (Na2S04) and the solvent evaporated in vacuo to afford the corresponding free base as an oil. lH NMR Free Base (CD3OD, 400 MHz) d 8.02(1H, d, J=8.3Hz), 7.81(1H, d, J=8.3Hz), 7.77(1H, d, J=8.3Hz), 7.74-7.66(3H,m), 7.46- 7.15(10H,m), 6.86(1H, s), 5.37(2H,m), 4.07(lH,m), 3.96 (1H, d, J=13.5Hz), 3.84 (1H, d, J=13.5Hz), 3.66 (1H, d, J=13.0Hz), 3.52 (1H, d, J=13.0Hz), 3.15(2H,m), 2.56(lH,dd, J=12.6 and 5.7 Hz), 2.37(lH,dd, J=12.6 and 5.7 Hz), 1.39(lH,m), 0.94(lH,m), 0.80(1H, m), 0.72(3H,d, J=7.0Hz) and 0.61(3H,t, J=7.0Hz) ppm. FAB HRMS exact mass calc'd for C37H39N5O 604.284314 (MH+), found 604.284876 Anal, calc'd for C37H38N5OCI 0.95H2O, 3.70TFA; C, 51.12 H, 4.21 N, 6.71. Found: C, 51.12; H, 4.18; N, 6.88. EXAMPLE 11 N-(2-Imidazolylmethyl )-N-naphth-l-vlmethvl-2(S)-((l-(4-cvanobenzyl)- lH-imidazol-5-yl)acetyl )amino-3(S)- methylpentanamine The title compound was prepared using the protocol described in Example 10 using 2-imidazole carboxaldehyde in place of 3- chlorobenzaldehyde. FAB HRMS exact mass calc'd for C34H38N7O 560.313784 (MH+), found 560.312362 Anal, calc'd for C37H38N5OCI 0.35H2O, 3.25TFA; C, 51.94 H, 4.41 N, 10.47. Found: C, 51.94; H, 4.41; N, 10.80. EXAMPLE 12 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(t- butoxycarbonvDamino- N-(naphth- 1 -ylmethyDpropionamide Step A: Preparation of [l-(Naphth-2-ylmethyl)-lH-imidazol-5- yl)l acetic acid methyl ester A solution of l-(Triphenylmethyl)-lH-imidazol-4-ylacetic acid methyl ester, the product of Example 1 step B, (4.36g, 11.4 mmol) and 2-(bromomethyl)naρhthalene in CH3CN (70 ml) was heated at 55°C for 4hr. After this time, the reaction was cooled to room temperature and the resulting imidazolium salt (white precipitate) was collected by filtration. The filtrate was concentrated to 30 ml and heated at 55°C for 18hr. After this time, the reaction was cooled to room temperature and the resulting white precipitate collected by filtration. The filtrate was concentrated to 10ml volume and heated at 55 °C for lhr. After this time, the reaction was again cooled to room temperature and diluted with ethyl acetate (25 ml). The resulting precipitate was collected by filtration and combined with the previous 2 precipitates in methanol (100 ml) and heated at reflux for 30min. The solvent was removed in vacuo and the resulting residue was partioned between methylene chloride(200 ml) and sodium bicarbonate (100 ml). The organic layer was evaporated in vacuo and the residue was purified by flash chromatography (Siθ2, 0-6% methanol in methylene chloride, gradient elution) to provide the title compound as an off white solid : lHNMR(CDCl3, 400 MHz) δ 7.82(2H, m), 7.75(1H, m), 7.70(1H, s), 7.49(3H, m), 7.20(1H, d, J=8.4Hz), 7.06(1H, s), 5.32(2H, s), 3.57(3H, s) and 3.49(2H, s) ppm. Step B: Preparation of 2-[l-(Naρhth-2-ylmethyl)-lH-imidazol-5- yllacetic acid hydrochloride 2-[l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl]acetic acid methyl ester (0.92g, 3.28mmol ) was dissolved in 2.5M hydrochloric acid ( 50ml ) and heated at 55°C for 3h. After this time, the solution was evaporated in vacuo to give the title compound as a white solid. lHNMR(CD30D, 400 MHz) δ 8.92(1H, s), 7.94(1H, d, J=8.6Hz), 7.88(2H, m), 7.83(1H, s), 7.54(3H, m), 7.43(1H, d, J=14Hz), 5.60(2H, s) amd 3.82(2H, s) ppm. Step C: Preparation of (R.S)-2.3-Diaminopropionic acid methyl ester A suspension of 2,3-diaminopropionic acid hydrobromide (15.3g, 82.7 mmol) in methanol (600 ml) was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature for 18hr. The solvent was evaporated in vacuo to afford the title compound as a pale yellow solid. lH NMR(d6 DMSO 400 MHz) δ 8.75(6H,s), 4.43(1H, t, J=6.1Hz), 3.80(3H, s) and 3.34(2H, s) ppm. Step D: Preparation of 3-(t-Butoxycarbonyl)amino-2-(RS)- aminopropionic acid methyl ester Di-t-butyldicarbonate (16.3 lg, 74.7 mmol) in methylene chloride (130ml) was added dropwise to (RS)-2,3-diamino propionic acid methyl ester (17.42g, 82.7 mmol) and triethylamine (46ml,330mmol) in methylene chloride (2.61) at -78°C. The reaction was then stirred at 0°C for 90min and quenched by addition of 10% aq. KHSO4 (150ml) . The aqueous layer was separated, and the pH adjusted to 10 with sat aq NaHC03 and 2.5M NaOH. The aqueous solution was extracted with methylene chloride and the combined extracts were dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue was purified by flash chromatography (Siθ2, 2.5%-8% methanol in EtOAc; gradient elution) to afford the title compound as an oil. lH NMR(CDC13, 400 MHz) δ 4.98(lH,s), 3.75(3H, s) and 3.58(1H, t), J=6.0Hz), 3.49(1H, m) and 3.26(lH,m) ppm. Step E: Preparation of 3-t-Butoxycarbonylamino-2-(RS)-[(Naphth-2- ylmethyl)- lH-imidazol-5-yl]acetylamino-propionic acid methyl ester. To a solution of 2-[l-(Naphth-2-ylmethyl)-lH-imidazol-5- yljacetic acid hydrochloride (3.83g, 12.7mmol), 3-t-butoxycarbonylamino-2(R,S)- aminopropionic acid methyl ester (3.33g, 15.3mmol), HOOBT (2.30g, 14.1mmol), and triethylamine (5.80ml, 42.0mmol) in DMF (150ml) at 0°C, was added EDC (2.67g, 13.9 mmol). The reaction was stirred at room temperature for 18hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3 , brine , dried (Na2S04), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 5% MeOH in CH2CI2) to afford the title compound as a white solid. iH NMR(CDCl3, 400 MHz) δ 7.81(1H, d, J=8.5Hz)),7.80-7.75(2H, m), 7.60(1H, s), 7.52(lH,s), 7.49(2H,m), 7.24(lH,d, J=8.5Hz), 7.06(lH,s), 6.86(1H, br d, J=3Hz), 5.32(2H,s), 4.74(lH,m), 4.45(lH,m), 3.73(3H,s), 3.52-3.40(4H,m), and 1.41(9H,s) ppm. FAB HRMS exact mass calc'd for C25H31N4O5 467.229445 (MH+), found 467.229649. Step F: Preparation of 3-t-Butoxycarbonylamino-2-(RS)-[(Naphth-2ι ylmethyl)- lH-imidazol-5-yllacetylaminopropionic acid. A solution of the methyl ester prepared in step E (4.80g, 10.3mmol ) in methanol (100ml) and 1 M lithium hydroxide (10.4 ml, 10.4 mmol) was stirred at 0°C for 18 hr. The pH was adjusted to pH 5 by the addition of IM HCl and the title compound was collected by filtration and dried in vacuo. lNMR(CD30D, 400 MHz) δ 8.15(1H, s), 7.72-7.82(3H,m), 7.70(lH,m), 7.50(2H, m), 7.34(lH,dd, J=8.2 and 1.8Hz), 7.16(lH,s), 5.49(2H,s), 4.34(lH,m), 3.59(2H,m), 3.48(lH,dd, J=14.0 and 4.5Hz), 3.34(lH,m) and 1.40(9H,s) ppm. FAB Mass spectmm, m/z = 453 (M+l). Step G: Preparation of 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol- 5-yl] acetyl }amino-3-(t-butoxycarbonyl)amino - N-(naphth- 1 -ylmethyl) propionamide To a solution of the acid prepared in step F (125mg, 0.276mmol), 1-naphthylmethylamine (39μl, 0.28mmol), HOBT (38.1mg, 0.28mmol), and triethylamine (40.0μl, 0.29mmol) in DMF (3.0ml) at 0°C, was added EDC (53.0mg, 0.28 mmol). The reaction was stirred at room temperature for 4hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3 , brine and dried (Na2S04). The solvent was evaporated in vacuo to afford the title compound. 1NMR(CDC13, 400 MHz) δ 7.92(lH,d, J=7.8Hz), 7.82(lH,d, J=8.2Hz), 7.80-7.65(4H,m),7.60-7.30(9H,m), 7.22(lH,t, J=5.4Hz), 7.05(lH,d, J=8.6Hz), 6.93(lH,s), 5.29(lH,t, J=5.7Hz), 5.06(lH,d, J=16.5Hz), 4.97(lH,d, J=16.5Hz), 4.83(lH,dd, J=14.8 and 5,8Hz), 4.76(lH,dd, J=14.8 and 5.3Hz), 4.38(lH,m), 3.50-3.25(4H,m) and 1.34(9H,s) ppm. FAB HRMS exact mass calc'd for C35H38N5O4 592.292380(MH+), found 592.293910. EXAMPLE 13 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(t- butoxycarbonvDamino- N-methyl-N-benzyl propionamide The title compound was prepared using the protocol described in Example 12, step G using N-methyl benzylamine in place of 1-naphthylmethylamine. lNMR(CDCl3 400 MHz) δ 7.84-7.74(3H,m), 7.62(0.7H,s), 7.58(0.3H,s), 7.52-7.42(3H,m), 7.38-7.26(2H,m), 7.24-7.10(2H,m), 7.07(0.7H,s), 7.01(0.3H,s), 6.67(0.7H,d, J=3.5Hz), 6.59(0.3H, d, J=3.5Hz), 5.32(1.4H,s), 5.28(0.6H,s), 5.0-4.85(2H,m) 4.75-4.45(2H,m), 3.52- 3.00(4H,m), 2.96(2. lH,s), 2.90(0.9H,s),1.42(6.3H, s) and 1.39(2.7H,s) ppm. F.AB Mass spectrum, m/z = 556(M+1). EXAMPLE 14 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyDamino- N-(2-methylbenzyl) propionamide The title compound was prepared using the protocol described in Example 12 step G using 2-methyl benzylamine in place of 1-naphthylmethylamine. lNMR(CD30D 400 MHz) δ 7.88-7.78(3H,m) 7.76(lH,s), 7.58(lH,s), 7.52-7.45(2H,m), 7.30-7.20(2H,m), 7.17-7.10(3H,m), 6.95(lH,s), 5.39(2H,m), 4.40(lH,m), 4.40(lH,d, J=15.0Hz), 4.32(lH,d, J=15.0Hz), 3.52(2H,s), 3.40-3.20(2H,m), 2.30(3H,s) and 1.40(9H,s) ppm. EXAMPLE 15 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyDamino- N-(3-methylbenzyl) propionamide The title compound was prepared using the protocol described in Example 12 step G using 3-methylbenzylamine in place of 1 -naphthylmethylamine. lNMR(CDCl3, 400 MHz) δ 7.85-7.72(3H,m) 7.56(lH,s), 7.52- 7.46(2H,m), 7.44(lH,s), 7.28(lH,m), 7.25-7.12(3H,m), 7.12-6.98 (3H,m), 6.90(lH,m), 5.26(lH,d, J=16Hz), 5.18(lH,d, J=16Hz), 4.30(lH,m), 3.50- 3.30(4H,m), 2.37(3H,s) and 1.42(9H,s) ppm. FAB Mass spectrum, m/z = 556(M+1). EXAMPLE 16 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(naphth-l-ylmethyl)propionamide hydrochloride. A solution of the product of Examplel2 (174mg, 0.294mmol) in CH2CI2 (10ml) and trifluoroacetic acid (5ml) was stirred at room temperature for 3hrs. The solvent was evaporated in vacuo, methanol (5ml) was added to the residue and the resulting solution saturated with gaseous HCl. The solvent was evaporated and the title compound was dried in vacuo. FAB Mass spectrum, m/z = 492(M+1). EXAMPLE 17 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-methyl-N-benzyl propionamide hydrochloride The title compound was prepared using the protocol described in Example 16 using the product from Example 13 lNMR(CD30D 400 MHz) δ 8.83(0.5H,s), 8.73(0.5H,s), 7.96- 7.80(3H,m), 7.70(lH,s), 7.60(7.44(3H,m), 7.38-7.12(6H,m), 5.59(lH,m), 5.38(lH,m), 5.23(0,5H,t, J=5.0Hz), 5.06(0.5H,t, J=5.0Hz), 4.74- 4.63(lH,m), 4.50-4.38(lH,m), 3.76(lH,s), 3.60-3.50(0.5H,m), 3.30- 3.20(1.5H,m), 3.10-3.00(lH,m), 2.92(1.5H,s), and 2.88(1.5H,s) ppm. FAB HRMS exact mass calc'd for C27H30N5O2 456.239951 (MH+), found 456.239252 EXAMPLE 18 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(2-methylbenzyl)propionamide hydrochloride The title compound was prepared using the protocol described in the Example 16 using the product of Example 14. F.AB Mass spectrum, m/z = 456(M+1). EXAMPLE 19 2(RS)-{ [l-(Naρhth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(3-methylbenzyl)propionamide hydrochloride The title compound was prepared using the protocol described in the Example 16 using the product of Example 15. FAB Mass spectmm, m/z = 456(M+1). EXAMPLE 20 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(3-methylbenzyl)propionamide To a solution of the amine from Example 19 (6.48mg, 0.0116mmol), and triethylamine (8.53μl, 0.0612 mmol) in CHCI3 (0.165ml) at 0°C, was added acetyl chloride (116μl of a 0.1M solution in CHCI3, 0.0116 mmol). The reaction was vortexed at room temperature, and allowed to stand at room temperature for 18 hrs. The solvent evaporated in vacuo and the residue was purified by preparative HPLC ( C-18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution), to afford the title compound after lyophilisation. FAB Mass spectmm, m/z = (M+l). EXAMPLE 21 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(naphth- 1 - ylmethvDpropionamide The title compound was prepared using the protocol described in the Example 20 using the amine from Example 16 and acetyl chloride. lNMR(CDCl3 400 MHz) δ 8.37(lH,s), 8.15(lH,m), 7.94(lH,d, J=8Hz), 7.90-7.70(5H,m), 7.60-7.45(4H, m), 7.40-7.35(2H,m), 7.35-7.25(2H,m), 7.20(1H, s), 7.12(lH,d, J=8.0Hz), 6.50(lH,m), 5.26(lH,d, J=15Hz), 5.14(lH,d, J=15Hz), 4.92(lH,m), 4.79(lH,dd, J=15.0 and 5.0Hz), 4.37(lH,m), 3.70-3.40(4H,m), and 1.85(3H,s) ppm. F.AB Mass spectrum, m/z = 534(M+1). EXAMPLE 22 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(2- methylpropionyPamino- N-(naphth- 1 -ylmethyDpropionamide The title compound was prepared using the protocol described in Example 20 using the amine from Example 16 and 2- methylpropionyl chloride instead of acetyl chloride. lNMR(CD30D 400 MHz) δ 8.89(lH,s), 8.60(lH,m), 8.03(lH,d, J=8.4Hz), 8.00-7.70(6H,m), 7.60-7.46(5H,m), 7.41(lH,dd, J=7.5 and 7.0Hz), 7.36(lH,dd, J=8.9 and 1.5Hz), 5.53(2H,m), 5.0-4.70(2H,m), 4.40(1H, t, J=6.0Hz), 3.71(2H,s), 3.43(2H,m), 2.31(1H, sept, J=6.8Hz), 1.01(3H,d,J=6.8Hz), and 0.99(3H,d, J=6.8Hz) ppm. FAB HRMS exact mass calc'd for C34H36N5O3 4562.281815 (MH+), found 562.281831 EXAMPLE 23 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH- ή nidazol-5-yl)] acetyl }amino-3- (phenylacetyl)amino- N-(naphth- 1 -ylmethvDpropionamide The title compound was prepared using the protocol described in Example 20 using the amine from Example 16 and phenylacetyl chloride instead of acetyl chloride. 1NMR(CDC13 400 MHz) δ 8.32(lH,s), 8.15(lH,d, J=5.7Hz), 7.92(lH,m), 7.86-7.70(5H,m), 7.60-7.44(5H,m), 7.38(2H,m), 7.30- 7.20(4H,m), 7.13(2H.d, J=6.8Hz), 7.08(2H,m), 6.58(lH,m), 5.17(lH,d, J=15,4Hz), 5.07(lH,d, J=15.4Hz), 4.84(lH,dd, J=15.0 and 5.5Hz), 4.75(lH,dd, J=15.0 and 5.5Hz), 4.40(lH,m), 3.60(lH,m), 3.47(lH,m) and 3.45-3.20(4H,m) ppm. FAB Mass spectmm, m/z = 610(M+1). EXAMPLE 24 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- (phenylacetyl)amino- N-methyl-N-benzyl) propionamide The title compound was prepared using the protocol described in Example 20 using the amine from Example 17 and phenylacetyl chloride instead of acetyl chloride. iH NMR(CDCl3, 400MHz) δ 8.85(0.5H,s), 8.74(0.5H,s), 8.00- 7.80(lH,m), 7.74(lH,s), 7.60-7.45(lH,m), 7.40-7.10(10H,m), 5.60(2H,m), 5.40(2H,m), 5.25(0,5H,t, J=5Hz), 5.10(0.5H,t, J=5.0Hz), 4.70(lH,dd, J=15 and 5.5Hz), 4.45(lH,dd, J=15.0 and 7.5Hz), 3.78(2H,m), 3.30(lH,m), 3.08(lH,m), 2.94(1.5H,s) and 2.88(1.5H,s) ppm. FAB HRMS exact mass calc'd for C35H36N5O3 3574.281815(MH+), found 574.281831. EXAMPLE 25 ri-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)l-N-butylacetamide To a solution of 2-[l-(Naphth-2-ylmethyl)-lH-imidazol-5- yl]acetic acid hydrochloride (89mg, 0.294mmol), n-butylamine (30μl, 0.30mmol), HOOBT (57mg, 0.35mmol), and triethylamine (140ml, 42.0mmol) in DMF (4ml) at 0°C, was added EDC (2.67g, 13.9 mmol). The reaction was stirred at room temperature for 18hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3, brine, dried (Na2Sθ4) and the solvent evaporated in vacuo to afford the title compound as a clear oil. iH NMR(CDCl3, 400 MHz) δ 7.86-7.74(3H, m),7.65(lH, m), 7.55- 7.45(3H, m), 7.22(lH,dd, J=8.6 and 2.0Hz), 7.04(lH,s), 5.30(lH,m), 5.25(2H,s), 3.46(2H,s), 2.95(lH,q, J=8Hz), 1.30-1.10(4H,m) and 0.83(3H,t, J=7.5Hz) ppm. FAB HRMS exact mass calc'd for C20H24N3O 322.191938 (MH+), found 322.191669. EXAMPLE 26 [l-(Naphth-2-ylmethyl)- lH-imidazol-5-yl)]- N-methyl-N-(3,3- diphenylpropyPacetamide Step A: Preparation of N-Benzyl-N-3.3-diphenylpropyl amine To a solution of 3,3-diphenylpropylamine (l.Olg, 4.79 mmol), acetic acid (28ml, 049mmol), and benzaldehyde (490μl, 4.80 mmol) in CH3CN (2 ml) was added sodium cyanoborohydride (4.80ml of a IM solution in THF, 4.8mmol) at 0°C. The reaction was allowed to warm to room temperature and stirred for 18hrs. The solvent was evaporated in vacuo, quenched with sat. aq. NaHCθ3 and extracted with EtOAc. The organic layer was washed with brine, dried (Na2Sθ4) and the solvent evaporated in vacuo. The residue was dissolved in MeOH (100ml) and sodium borohydride (182mg, 5.55mmol) added and the reaction was stirred for 30min. The solvent was evaporated and the residue treated with sat. aq. NaHCθ3 and extracted with EtOAc. The organic layer was separated, washed with saturated brine, dried( Na2Sθ4) and the solvent evaporated in vacuo to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 7.40-7.00 (15H, m), 4.04(lH,t, J=7.5Hz), 3.62(2H,s), 2.62(2H,t, J=7.0Hz) 2.26(2H,q, J=7.5Hz) ppm. Step B: Preparation of N-Benzyl-N-methyl-3.3-diphenylpropylamine To a solution of N-benzyl-3,3-diρhenylpropylamine (1.29g, 4.30mmol) and 30% aq. formaldehyde (1.50ml, 20 mmol) in CH3CN:H2θ (2:1, v/v, 40 ml) was added sodium cyanoborohydride (563mg , 8.96mmol) at 0°C. The reaction was allowed to warm to room temperature and stirred for 90min. The organic solvent was evaporated, and the residue diluted with water and extracted with CH2CI2. The organic extracts were washed with brine, dried (Na2S04) and the solvent evaporated in vacuo to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 7.40-7.00 (15H, m), 4.05(lH,t, J=7.5Hz), 3.44(2H,s), 2.38-2.22(4H,m) and 2.16(3H,s) ppm. Step C: Preparation of N-Methyl-3.3-diphenylpropylamine A solution of N-benzyl-N-methyl-3,3-diphenylpropylamine (1.03g, 3.27mmol) in methanol (35ml) and aq. HCl (0.27ml, of a 12. IM aq. solution, 3.3mmol) was purged with argon and palladium hydroxide (405mg) added. The flask was evacuated and shaken under an atmosphere of hydrogen (50psi) for 18hrs. The hydrogen was replaced by argon and the catalyst removed by filtration. The filtrate was treated with aq. NaOH (100ml of a IM solution) and extracted into Et2θ. The organic extracts were dried (Na2S04) and evaporated in vacuo to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 7.32-7.14 (10H, m), 4.05(lH,t, J=7.5Hz), 2.54(2H, t, J=7.1Hz), 2.38(3H,s) and 2.24(2H,m) ppm. FAB Mass spectmm, m/z = 226 (M+l). Step D: Preparation of [ 1 -(Naρhth-2-ylmethyl)- 1 H-imidazol-5-yl) ]- N-methyl-N-3.3- diphenylpropyl acetamide To a solution of 2-[l-(Naphth-2-ylmethyl)-lH-imidazol-5- yTJacetic acid hydrochloride (160.8mg, 0.531mmol),N-methyl-3,3- diphenylpropylamine (104mg, 0.462mmol) HOOBT (81mg, 0.50mmol), and triethylamine (215ml, 1.54mmol) in DMF (5ml) at 0°C, was added EDC (94.3mg, 0.50mmol). The reaction was stirred at room temperature for 18hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHC03, brine, dried (Na2Sθ4) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC ( C-18; 95:5 to 5:95 water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution), to afford the title compound after lyophilisation. iH NMR(CDCl3, 400 MHz) d 8.45(1H, d, J=11.4Hz), 7.90-7.82(2H, m), 7.82-7.74(lH,m), 7.64-7.50(3H,m), 7.32-7.16(9.5H,m), 7.09(2H,d, J=7.8Hz), 6.98(0.5H,s),5.45(lH,s), 5.40(lH,s), 3.90(0.5H,d, J=7.5Hz), 3.75(0.5H,d, J=7.5Hz), 3.40(lH,s), 3.37(lH,m), 3.22(lH,dd, J=5.6 and4.6Hz), 3.12(lH,s), 2.93(1.5H,s), 2.77(1.5H,s), 2.30(lH,m), and 2.20(lH,m) ppm. FAB HRMS exact mass calc'd for C32H32N3O 474.253538 (MH+), found 474.255055. EXAMPLE 27 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyPamino - N-methyl-N-benzyl propionamide Step A: Preparation of 3-t-Butoxycarbonylamino-2-(RS)- [ 1 -(4- cyanobenzyl)- lH-imidazol-5-yl]acetylamino-propionic acid methyl ester To a solution of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid (607mg, 1.64mmol), 3-t-Butoxycarbonylamino-2(RS)- aminopropionic acid methyl ester (352mg, l.όlmmol), HOOBT (319mg, 1.96mmol), and triethylamine (0.54ml, 3.87mmol) in DMF (13ml) at 0°C, was added EDC (2.67g, 13.9 mmol). The reaction was stirred at room temperature for 18hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHC03, brine, dried (Na2Sθ4). and the solvent evaporated in vacuo to afford the title compound as a white solid. iH NMR(CDCl3, 400 MHz) d 7.65(2H, d, J=8.5Hz), 7.55((1H, s), 7.21(1H, d, J=8.5Hz), 7.07(lH,s), 5.28(2H,m), 4.78(1H, m), 4.49(lH,m), 3.78(3H,s), 3.60-3.44(3H,m), 3.44(lH,d,J=16.0Hz), 3.36(lH,d,J=16.0Hz) and l.43(9H,s) ppm. Step B: Preparation of 3-t-Butoxycarbonylamino-2-(RS)-[l-(4- cyanobenzyP- 1 H-imidazol-5-yll acetylamino-propionic acid A solution of the methyl ester from Step A (604mg, 1.37mmol ) in methanol (14ml) and 1 M lithium hydroxide (1.40 ml, 1.40 mmol) was stirred at 0°C for 18 hr. The reaction was quenched by the addition of IM HCl (1.40ml) and the solvent was evaporated in vacuo to afford the title compound and lithium chloride which was used as is. iH NMR(CD3θD, 400 MHz) δ 8.03QH, s), 7.74(2H,d, J=8.4Hz), 7.35(2H,d, J=8.4Hz), 7.11(lH,s), 5.41(2H,s), 4.34(lH,m), 3.60- 3.45(3H,m), 3.36(lH,m) and 1.41(9H,s) ppm FAB HRMS exact mass calc'd for C21H25N5O5 428.193394 (MH+), found 428.193423. Step C: Preparation of 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5- yl] acetyl} amino -3-(t-butoxycarbonyl)amino-N-methyl-N- benzyl propionamide To a solution of the acid from Step B(163.5mg, 0.348mmol), N-methylbenzylamine (45μl, 0.29mmol), HOOBT (58.4mg, 0.358mmol), and triethylamine (lOO.Oμl, 0.29mmol) in DMF (3.6ml) at 0°C, was added EDC (55.4mg, 0.289 mmol). The reaction was stirred at room temperature for 4hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHC03, brine, dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 5% -7.5% MeOH in CH2C12; gradient elution) to afford the title compound as a white solid. iH NMR(CD3θD, 400 MHz) δ 8.10-7.70(3H, m), 7.40-7.20(7H, m), 6.97(0.66H,s), 6.91(0.33H,s), 5.42-5.28(2H,m), 5.08(0.33H, m), 4.86(0.66H,m), 4.76-4.42(2H, m), 3.55-3.20(4H,m), 3.08(2H,s), 2.84(lH,s), 1.42(6H,s) and 1.40(3H, s) ppm. FAB HRMS exact mass calc'd for C29H34N6O4 531.271979(MH+), found 531.270872. EXAMPLE 28 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino-3-(t- butoxycarbonyl)amino-N-(3-methylbenzyl) propionamide The title compound was prepared using the protocol described in the Example 27 step C using 3-methylbenzylamine in place of N-methylbenzylamine. iH NMR(CD3θD, 400 MHz) δ 7.75(1H, s), 7.68(2H,d, J=8.4Hz), 7.26(2H,d, J=8.4Hz), 7.19(lH,t, J=7.7Hz), 7.12(1H, s), 7.07(2H,t, J=6.0Hz), 6.95(lH,s), 5.33(2H,m), 4.87(lH,m), 4.38(3H, m), 4.31(lH,d, J=15.2Hz), 3.47(2H,s), 2.32(3H,s) and 1.42(9H,s) ppm. FAB HRMS exact mass calc'd for C29H34N6O4 531.271979(MH+), found 531.271895. EXAMPLE 29 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino-3-(t- butoxycarbonyl)amino-N-(naphth- 1 -ylmethyl) propionamide The title compound was prepared using the protocol described in Example 27 step C using 1-naphthylmethylamine in place of N-methylbenzylamine. iH NMR(CD3θD, 400 MHz) δ 8.04(1H, d, J=8.5Hz), 7.89(1H, d, J=7.0Hz), 7.81(lH,d, J=8.0Hz), 7.72(lH,s), 7.68(2H, d, J=7.4Hz), 7.58- 7.38(4H, m), 7.23(2H, d, J=7.4Hz), 7.07(2H,t, J=6.0Hz), 6.95(lH,s), 5.28(2H,m), 4.87(2H,m), 4.40(1H, m), 3.47(2H,s), 3.40-3.20(2H,m) and 1.42(9H,s) ppm. FAB HRMS exact mass calc'd for C29H35N6O4 567.271979(MH+), found 567.269604. EXAMPLE 30 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-3-amino - N-methyl-N-benzyl- propionamide A solution of the product from Example 27 (86.3mg, 0.163 mmol) in EtOAc (5ml) at 0°C was saturated with gaseous HCl and stirred for 15 min. The solvent was evaporated and the title compound was dried in vacuo. - Il l - iH NMR(d6 DMSO, 400 MHz) δ 9.20-9.00(2H,m), 8.20(3H,s), 7.88(lH,d,J=7.5Hz), 7.65-7.10(6H,m), 5.60-5.40(2H,m), 5.15-5.00(lH,s), 4.70-4.40(2H, m), 3.80-3.00(4H,m), 2.94(2H,s) and 2.78(lH,s) ppm. FAB HRMS exact mass calc'd for C24H27N6O4 431.219549 (MH+), found 431.218412. EXAMPLE 31 2(RS)- { [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl] acetyl } amino-3-amino- N-(3-methylbenzyl) propionamide The title compound was prepared using the protocol described in Example 30 using the product from Example 28. iH NMR(d6 DMSO, 400 MHz) δ 9.12(lH,m), 8.86(1H, d,J=7.6Hz), 8.73(lH,t, J=5.7Hz), 8.20(3H,m), 7.87(2H,d, J=8.7Hz), 7.60(lH,s), 7.47(2H,d, J=8.7Hz),7.19(lH,t, J=7.2Hz), 7.10-7.00(3H,m), 5.53(2H,m), 4.56(lH,m), 4.27(2H,m), 3.73(2H,s), 3.23(lH,m), 2.90(lH,m) and 2.26(3H,s) ppm. FAB HRMS exact mass calc'd for C24H27N6O2 431.219549 (MH+), found 431.219835. EXAMPLE 32 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino - N-(naphth- 1 -ylmethyl) propionamide The title compound was prepared using the protocol described in Example 30 using the product from Example 29. iH NMR(d6 DMSO, 400 MHz) δ 9.12(lH,m), 8.92(1H, d,J=7.6Hz), 8.81(lH,t, J=5.7Hz), 8.22(3H,m), 8.04(lH,m), 7.92(lH,m), 7.88-7.80(3H, m), 7.58(lH,s), 7.52(2H,m), 7.48-7.38(4H,m), 5.51(2H,m), 4.74(2H,m), 4.57(lH,m), 3.73(2H,s), 3.20(lH,m) and 3.01(lH,m)ppm. FJAB HRMS exact mass calc'd for C27H27N6O2 467.219549MH+), found 467.219920. EXAMPLE 33 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-3- (phenylacetyl)amino - N-methyl-N-benzyl) propionamide To a solution of the product from Example 30 (42.5mg, 84.4mmol), and triethylamine (58μl, 420 mmol) in CHC13 (0.85ml) at 0°C, was added phenylacetyl chloride (11.2μl 84.4 mmol). The reaction was vortexed and allowed to stand at room temperature for 18hrs. The reaction was diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3, brine and dried (Na2S04). The solvent evaporated in vacuo and the residue was purified by preparative HPLC ( C-18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution), to afford the title compound as a white solid. iH NMR(CD30D, 400 MHz) δ 8.95(0.67H,d, J=1.7Hz,), 8.92(0.33H, d, J=1.7Hz), 7.76(0.67H, d, J=8.7Hz), 7.75(1.33H, d, J=8.7Hz), 7.51(0.67H, s), 7.44(2H,d, J=8.7Hz), 7.38-7.20(10.33H,m), 5.55-5.37(2H,m), 5,12(0.33H, dd, J=4.0 and 3.0Hz),4.98(0.67H, dd, J=4.0 and 3.0Hz), 4.94-4.66(lH,m), 4.76(0.67H, dd, J=10.4Hz), 4.28(0.33H, d, J=10.4Hz), 3.64-3.36(5H,m), 2.98(2H,s), and 2.83(lH,s) ppm. FAB HRMS exact mass calc'd for C32H33N6O3 549.261414(MH+), found 549.262581. EXAMPLE 34 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-3- (acetyPamino - N-(naphth-l-yl methyPpropionamide To a solution of the product from Example 32 (37.3mg, 69.1mmol), and triethylamine (52μl, 345 mmol) in CHCI3 (0.85ml) and DMF (0.5ml) at 0°C, was added acetyl chloride (5.0μl 69.1 mmol). The reaction was vortexed and allowed to stand at room temperature for 18hrs. The reaction was diluted with EtOAc and the organic layer washed with sat. aq NaHC03, brine and dried (Na2S04). The solvent evaporated in vacuo and the residue was purified by preparative HPLC ( C-18; 95:5 to 5:95 Water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution), to afford the title compound as a white solid. iH NMR(CD30D, 400 MHz) δ 8.95(lH,d, J=1.0Hz,), 8.06 (IH, d, J=6.6Hz), 7.89(1H, d, J=7.0Hz), 7.89(1H, d, J=7.0Hz), 7.82(1H, d, J=8.4Hz), 7.54(2H,d, J=8.4Hz), 7.60-7.48(5H,m), 7.43(2H,t, J=7.9Hz), 5.58(2H,m), 4.98-4.70(2H,m), 4.43(lH,dd, J=6.4 and 5.1Hz), 3.72(lH,d, J=16.0Hz), 3.65(1H, d, J=16.0Hz), 3.54(1H, dd, J=13.6 and 4.5Hz), 3.42(1H, dd, J=13.6 and 6.4Hz) and 1.86(3H,s)ppm. FAB HRMS exact mass calc'd for C29H29N6O3 509.230114(MH+), found 509.229190. EXAMPLE 35 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-3-(2- methylpropionvPamino - N-(naphth-l -ylmethyl) propionamide The title compound was prepared using the protocol described in Example 34 using isobutyryl chloride in place of acetyl chloride. iH NMR(CD3θD, 400 MHz) δ 8.96(lH,d, J=1.0Hz,), 8.06 (IH, d, J=8.6Hz), 7.99(1H, d, J=8.6Hz), 7.82(1H, d, J=7.9Hz), 7.74(2H, d, J=8.6Hz), 7.58-7.48(5H,m), 7.43(2H,t, J=7.9Hz), 5.52(lH,d, J=15.2Hz), 5.47(lH,d, J=15.2Hz), 4.98-4.70(2H,m), 4.44(lH,dd, J=5.8 and 5.0Hz), 3.70(lH,d, J=13.9Hz), 3.66(1H, d, J=13.9Hz), 3.50(1H, dd, J=13.6 and 3.0Hz), 3.42QH, dd, J=13.6 and 6.4Hz), 2.34(lH,sept, J=6.8Hz), 1.04(3H,d, J=6.8Hz) and 1.02(3H,d, J=6.8Hz)ppm. FAB HRMS exact mass calc'd for C31H33N6O3 537.261414 (MH+), found 537.262247. EXAMPLE 36 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(2- methylpropionyPamino - N-(naphth-l -ylmethyl) propionamide The title compound was prepared using the protocol described in Example 34 using phenylacetyl chloride in place of acetyl chloride. iH NMR(CD30D, 400 MHz) δ 8.72(lH,s), 7.94 (IH, d, J=7.4Hz), 7.79(1H, d, J=7.6Hz), 7.72(1H, d, J=8.4Hz), 7.62(2H, d, J=8.3Hz), 7.48- 7.22(7H,m), 7.22-7.08(5H,m), 5.34(lH,d, J=15.7Hz), 5.28(lH,d, J=15.7Hz), 4.90-4.60(2H,m), 4.38(lH,dd, J=5.0 and 4.2Hz), 3.46(2H,s), 3.40(2H, m) and 3.34(2H,s)ppm. FAB HRMS exact mass calc'd for C35H33N6O3 585.261414 (MH+), found 585.260592. EXAMPLE 37 N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl1-N-(l-naphthylmethyl)glycine isopropylamide Step A: Preparation of N-(2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyl) gly cine methyl ester. Glycine methyl ester hydrochloride (4.41 g, 0.035 mol) was dissolved in 1,2-dichloroethane (50 mL) and DMF (5 mL) and treated with 3 A molecular sieves (10 g) and N-t-butoxycarbonyl-isoleucinal (6.3 g, 0.029 mol) with stirring at 0°C. Sodium triacetoxyborohydride (9.27 g, 0.044 mol) was added, and the pH of the mixture was adjusted to 6 with triethylamine (3 ml, 0.022 mol). After stirring for 18 h the mixture was filtered, concentrated and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with aqueous saturated NaHCθ3 solution, brine, and dried (Na2S04). Filtration and evaporation in vacuo afforded a residue which was purified by flash chromatography (Siθ2, EtOAc:hexane, 1:3) to give the title compound as an oil. iH NMR (CDC13 400MHz) δ 4.69 (IH, m), 3.72 (3H, s), 3.48-3.62 (IH, m), 3.42 (2H, m), 2.65 (2H, d, J=6Hz), 1.4-1.6 (2H, m), 1.48 (9H, s), 1.04-1.2 (IH, m), 0.85-0.95 (6H, m)ppm. Step B: Preparation of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyll-N-(l-naphthylmethyl)glycine methyl ester N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl] glycine methyl ester (2.00 g, 6.97 mmol) was dissolved in 1,2- dichloroethane (56 ml) and 3A molecular sieves were added followed by 1-naphthaldehyde (1.89 ml, 13.9 mmol) and sodium triacetoxyborohydride (6.65 g, 31.4 mmol). The mixture was stirred at ambient temperature for 16 h, filtered and evaporated in vacuo. The residue was partitioned between EtOAc (100 ml) and sat. aq. NaHCθ3 (25 ml). The aqueous layer was extracted with EtOAc (3x50 ml). The organic extracts were combined, dried (Na2Sθ4), filtered, and evaporated in vacuo to afford a residue which was purified by chromatography (Siθ2 , 15-33% ethyl acetate in hexanes) to afford the title compound as an oil. iH NMR (CD3OD, 400MHz) δ 8.44-8.38 (IH, d, J=6Hz), 7.88-7.77 (2H, m,), 7.55-7.35 (4H, m), 6.34-6.27 (IH, m), 4.25 (2H, m), 3.66 (3H, s), 3.40-3.23 (IH, m), 2.95-2.85 (IH, dd, J=6 and 15Hz), 2.68-2.57 (IH, dd, J=6 and 15Hz), 1.57-1.46 (IH, m), 1.43 (9H, s), 1.34-1.18 (2H, m), 1.06- 0.85 (IH, m) and 0.85-0.71 (6H, m)ppm. Step C: Preparation of N-[2(S)-(Amino)-3(S)-methylpentyl]-N-(l- naphthylmethyl) glycine methyl ester hydrochloride A solution of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl) glycine methyl ester (5.90g, 13.8 mmol) in EtOAc (100 ml) was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature for lhr. The solvent was evaporated in vacuo to afford the title compound as a white solid. iH NMR(CD3θD 400 MHz) δ 8.26(1H, d, J=8.6Hz),7.92(lH, d, J=7.2Hz), 7.87(1H, d, J=8.6Hz), 7.63-7.42(4H,m), 4.34(lH,d, J=12.3Hz), 4.26(lH,d, J=12.3Hz), 3.68(3H,s), 3.13(1H, d, J=10.3Hz), 2.67- 2.55(2H,m), 1.46(lH,m), 1.28(2H,m), 1.10-0.90(2H,m), 0.84(3H,d,J=6.8Hz) and 0.77(3H,t, J=6.8Hz)ppm. Step D: Preparation of N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol- 5- yl] acetylamino)-3(S)-methylpentyl]-N-(l- naphthylmethyl) glvcine methyl ester To a solution of 2-[l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetic acid (220mg,0.533mmol) and the amine hydrochloride salt from step C (212mg,0.533mmol), HOBT (72mg, 0.533mmol), and N- methylmorpholine (117μl, l.llmmol) in DMF (2ml) was added EDC (764mg, 3.99 mmol). The reaction was stirred at room temperature for 72hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHCθ3 , brine, dried (Na2S04). and evaporated in vacuo. The residue was chromatographed (Siθ2, 3-4% MeOH in CH2CI2, gradient elution) to afford the title compound as a white solid. !H NMR(CD30D, 400 MHz) δ 8.30(lH,d, J=8.4Hz), 7.84(lH,d, J=8.0Hz), 7.80(lH,t, J=4.5Hz), 7.68-7.38(3H,m), 7.48- 7.32(4H,m), 7.10(2H,d, J=8.0Hz), 6.87(lH,s), 5.24(lH,d, J=16.7Hz), 5.18(lH,d,J=16.7Hz), 4.83(2H,s), 4.27(lH,d, J=12.8Hz), 4.10(lH,d, J=12.8Hz), 3.97(lH,m), 3.65(3H,s), 3.40-3.20(2H,m), 2.92(lH,dd, J=13.3 and 4.3Hz), 2.60(lH,dd, J=13.3 and lO.OHz), 1.48(lH,m), 1.25(lH,m), 0.98(lH,m), 0.78(3H,d, J=6.8Hz) and 0.77(3H,t, J=7.5Hz) ppm. Anal, calc'd for C33H37N5O3 1.05H2O, 2.85 TFA C, 51.90; H, 4.72; N, 7.82. Found: C, 51.90; H, 4.70; N, 8.18. FAB Mass spectmm, m/z = 552 (M+l). Step E: Preparation of N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol- 5-yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl) glvcine A solution of the methyl ester from step D (2.32g, 4.21 mmol) in MeOH(20ml) and 1 M lithium hydroxide (4.70 ml, 4.70 mmol) was stirred at RT for 6hr. The aqueous solution diluted with water (15ml) and extracted with EtOAc (100ml), dried (Mg2Sθ4), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 20% MeOH in CH2CI2) to afford the title compound as a white solid. iH NMR(CD30D, 400 MHz) δ 8.33(1H, d,J=8.3Hz), 7.87(2H,d, J=7.7Hz), 7.78(lH,s), 7.63(2H,d, J=6.6Hz), 7.57(lH,d, J=6.4Hz), 7.50-7.38(4H,m), 7.17(lH,d, J=8.3Hz), 6.96(lH,s), 5.32(lH,d, J=16.6Hz), 5.25(lH,d,J=16.6Hz), 4.64(lH,d, J=13.2Hz), 4.40(lH,d, J=13.2Hz), 3.99(lH,m), 3.60-3.28(4H,m), 3.22(lH,dd, J=13.3 and 3.1Hz), 2.93(lH,dd, J=13.3 and 10.3Hz), 1.52(lH,m), 1.29(lH,m), 1.06(lH,m), 0.86-0.76(6H,m) ppm. Anal, calc'd for C32H35N5O3 I.OOH2O, C, 69.17; H, 6.71 N, 12.60. Found: C, 68.95; H, 6.37; N, 12.54. FAB Mass spectmm, m z = 538 (M+l). Step F: Preparation of N-[2(S)-([ l-(4-Cyanobenzyl)- 1.H- imidazol-5-yl]acetylamino)-3(S)-methylpentyl]-N-( 1 - naphth ylmethyl) glycine isopropylamide To a solution of the acid from step E (50mg, 0.093mmol) and isopropyl amine (212mg,0.533mmol), HOBT resinl (93mg, 1.08mmol g ; O.lOOmmol), in CH2CI2 (1.1ml) was added DCC (23.0mg, 1.12 mmol). The reaction was stirred at room temperature for 20min, the resin bound active ester was isolated by filtration and washed with CH2CI2 (100ml) and isopropanol: CH2C12 (1:1), (50ml) and dried in vacuo. This resin was added to a solution of isopropylamine (7.0ml, O.Oδmmol) in CH2CI2 (0.6ml) and stirred at room temperature for 20min. The resin was removed by filtartion, the filtrate evaporated, and the residue purified by chromatography (Siθ2, 3% MeOH in CH2CI2) to afford the title compound as a white solid. iH NMR(CDC13, 400 MHz) δ 8.33(1H, m),7.79(lH,m), 7.84(lH,d, J=8.2Hz), 7.61(2H,d, J=8.4Hz), 7.50-7.40(4H,m), 7.37(lH,d, 5.9Hz), 7.05(2H, d, J=8.5Hz), 6.81(1H, d, J=7.4Hz), 6.57(lH,s), 5.19(lH,d, J=9.3Hz), 5.11(2H,m), 4.27(lH,d, J=12.7Hz), 4.05-3.85(2H,m), 3.71(lh,d, j=12.9Hz), 3.32(lH,d, J=13.4Hz), 3.06(1H, d, J=13.4Hz), 2.95(lH,d, j=12.4Hz), 2.81(lH,d J=12.4Hz), 2.53(1H, dd, J=13.5 and 3.4Hz), 2.44(lH,dd, J=13.5 and 9.6Hz), 1.70-1.60(lH,m), 1.37(lH,m), 1.15(lH,m), 1.05(3H,d, J=6.5Hz) 1.01(3H,d, J=6.5Hz), 0.78(3H,t, J=6.2Hz, 0.71(3H,d, J=6.7Hz) ppm. FAB HRMS exact mass calc'd for C35H43N6O2 579.344750(MH+), found 579.343531. 1. Prepared as described by A Berrada, F. Cavelier, R. Jacquier and J. Verducci in Bulletin de la Societe Chimique de France . 4, 513-314, 1989. EXAMPLE 38 N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyll-N-(l-naphthylmethyl)glycine ρiρeridinylamide The title compound was prepared using the protocol described in Example 37 step F using piperidine in place of isopropylamine. iH NMR(CDCl3, 400 MHz) δ 8.11(1H, d, J=8.0Hz), 7.82(lH,d, J=7.9Hz), 7.80-7.74(2H,m), 7.55(2H,d, J=8.2Hz), 7.48-7.30(5H,m), 7.05(2H,d, J=8.0Hz), 6.97(lH,s), 5.27(lH,d, J=16.0Hz), 5.22(lH,d, J=16.0Hz), 4.28(lH,d, J=13.5Hz), 4.00(lH,m), 3.90(lH,d, J=13.5Hz), 3.58(lH,m),3.30(2H,s), 3.16(lH,d, J=15.7Hz), 3.20(lH,d, J=15.7Hz), 3.15(lH,m), 3.05(lH,m), 2.76-2.60(2H,m), 1.82(lH,m), 1.70- 1.20(8H,m), 1.07(lH,m), 0.88(3H,t, J=7.3Hz) and 0.76(3H,d,J=6.8Hz) ppm. EXAMPLE 39 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyPamino - N- methyl-N-(naphth-l -ylmethyl) propionamide The title compound was prepared using the protocol described in the Example 27 step C using N-methylnaphth-1- ylmethylamine in place of N-methylbenzylamine. iH NMR(CD3θD, 400 MHz) δ 8.96( 0.75H,s), 8.82(0.25H,s), 8.47(0.75H,d, J=8Hz), 8.42(0.25H,d, J=8Hz), 8.07-7.70(5H,m), 7.60- 7.20(13H,m), 5.51(1.5H,s), 5.30(0.5H,s), 5.20-5.00(2H,m), 5.00- 4.60(lH,m), 3.73(lH,m), 3.60-3.20( 3H,m), 3.09(2.25H,s), 2.99(.75H,s), 1.40(6.75H,s) and 1.37(2.25H,s) ppm. FAB Mass spectmm, m/z = 581 (M+l) EXAMPLE 40 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S){N * - methanesulfonyl-N'-(naphth-l-ylmethyl)aminomethyl)-pyrrolidine Step A: Preparation of 2(S)-Hydroxymethyl-N-trifluoroacetyl pyrrolidine To a solution of L-prolinol (7.02g, 69.4mmol) and triethylamine (10.6ml, 76.1mmol) in CH2CI2 (700ml) at -5°C was added trifluoroacetic anhydride (9.80ml, 69.4mmol) over a period of 4hr. The solvent was evaporated in vacuo and the residue purified by chromatography(Si02, 15-20% EtOAc in hexanes, gradient elution). The title compound was obtained as a pale yellow oil. iH NMR(CDCl3, 400 MHz) δ 4.27( lH,m), 3.84-3.56(4H,m), 3.19QH, dd, J=7.8 and 3.6Hz) and 2.20-1.74(4H,m) ppm. FAB Mass spectmm, m/z = 198 (M+l) Step B: Preparation of 2(S)-Methanesulfonyloxymethyl-N- trifluoroacetyl pyrrolidine To a solution of the product of step A (1.002g, 5.08mmol) and triethylamine (0.78ml, 5.60mmol) in CH2CI2 (50ml) at -25°C was added methane sulfonyl chloride (0.40ml, 5.17mmol) over a period of 5 min and stirring was continued for lhr. The solvent was evaporated in vacuo and the residue purified by chromatography(Si02, 33% EtOAc in hexanes, elution). The title compound was obtained as a colorless oil. iH NMR(CDCl3, 400 MHz) δ 4.54(lH,dd, J=4.9 and 10.2Hz), 4.38(lH,m), 4.31(lH,dd, J=3.8 and 10.2Hz), 3.71(2H,m), 3.01(3H,s), 2.20- 1.90(4H,m) ppm. FAB HRMS exact mass calc'd for C8H13NO4SF3 276.051740(MH+), found 276.051233. Step C: Preparation of 2(S Azidomethylpyrrolidine In a flask protected by a safety screen, a solution of the product of stepB (12.27g, 0.042mmol) and lithium azide (2.47g, 0.051mmol) in DMF (30ml) was stirred at 45°C for 18hr. The solvent was evaporated in vacuo and the residue triturated with EtOAc (100ml) and filtered. The filtrate was evaporated in vacuo and the residue dissolved in MeOH (255ml) which was saturated with gaseous ammonia at 0°C and then stirred at room temperature for 72hr. The solvent was removed by distillation in vacuo to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 3.40-3.20(3H,m), 3.05-2.85(2H,m), 2.20- 1.60(3H,m), 1.50-1.35(lH,m)ppm. Step D: Preparation of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- yPacetyl 1- 2(S)-azidomethyπ-pyrrolidine To a solution of the acid from Example 1 step D (3.00g, 10.57mmol), the amine from step B (2.13g, 11.63mmol), HOOBT (1.90 g, 11.63mmol), and triethylamine (1.62ml, 11.63 mmol) in DMF (20ml) was added EDC (2.23g, 11.63 mmol). The reaction was stirred at room temperature for 24hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHC03 , brine , dried (MgSθ4). and evaporated in vacuo. The residue was purified by chromatography (Siθ2, 32-4% MeOH in CH2CI2, gradient elution) to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 7.64(2H,d, J=7.0Hz), 7.52(lH,s), 7.17(2H,d, J=7.0Hz), 6.97(lH,s), 5.35(2H,m), 4.14(lH,m), 3.69(lH,dd, J=12.1 and5.5Hz), 3.60-3.20(5H,m), and 2.20-1.80(4H,m) ppm. Step E: Preparation of N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5- yPacetyl } - 2(S)-aminomethyl } -pyrrolidine A solution of the azide from step D (480mg, 1.37mmol) in methanol (20ml) was purged with argon and 10% palladium on carbon (20mg) added. The flask was evacuated and stirred under an atmosphere of hydrogen (2 atm) for 3hrs. The hydrogen was replaced by argon and the catalyst removed by filtration and the solvent evaporated in vacuo to afford the title compound as an oil. A portion of this material was converted to the trifluoroacetate salt. iH NMR(CD3θD, 400 MHz) Trifluoroacetate salt δ 8.88(lH,s), 7.74(2H,d, J=8.3Hz), 7.49(lH,s), 7.45(2H,d, J=8.3Hz), 5.50(2H,s), 4.18(lH,m), 3.90-3.80(2H,m), 3.60-3.40(2H,m), 3.15-2.95(2H,m) and 2.20- 1.70(4H,m) ppm. Step F: Preparation of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- yl)acetyl } - 2(S) { N'-(naphth- 1 -ylmethyl)aminomethyl } - pyrrolidine To a slurry of 1-naphthaldehyde (197μl, 1.63 mmol), cmshed 3 A molecular sieves (l.Og), and the amine from step E (421mg, 1.30 mmol) in 1,2-dichloroethane (10 ml) was added sodium triacetoxyborohydride (345 mg, 1.63 mmol) at 0°C. The reaction was allowed to warm slowly to RT and stirred for 24 hrs. The reaction was cooled to 0°C and quenched with sat. aq. NaHCθ3 and stirred for 30min. The organic layer was separated, washed with saturated brine, dried (MgSθ4) and evaporated in vacuo. The residue was purified by chromatography on a chromatatron (Siθ2, 5% MeOH in CH2CI2) to provide the title compound as an oil. 1HNMR(CDC13, 400 MHz) δ 8.40-6.70(13H,m), 5.40-5.20(2H,m), 4.30- 4.10(2H,m), 3.60-3.40(5H,m),2.95-2.60(2H,m), 2.40-1.80(4H,m) ppm. Step G: Preparation of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- yl)acetyl }- 2(S)-{ N'-memanesulfonyl-N'-(naphth- 1- ylmethyPaminomethyl } -pyrrolidine To a solution of the product of step F (74mg, 0.16 mmol) in CH2CI2 (2 ml) and triethylamine (22μl, O.lόmmol) at 0°C was added methanesulfonyl chloride(12.3μl, 0.16mmol). The reaction was stirred at room temperature for lhr,quenched with sat aq. NaHCθ3 and extracted with CH2CI2 (2x 10ml). The organic extracts were dried (MgS04) and the solvent evaporated in vacuo.The residue was purified by preparative HPLC (C-18; 95:5 to 5:95 water:CH3CN containing 0.1% trifluoroacetic acid; gradient elution). Lyophilisation of the collected fractions afforded the title compound as a white solid. iH NMR(CD3θD, 400 MHz) δ 8.92(1H, m), 8.36(1H, m), 8.00- 7.30(llH,m), 5.46(1.2H,s), 5.39(0.8H,s), 5.03(0.6H,d, J=14.5Hz), 4.90- 4.60(lH,m), 4.71(0.4H,d, J=14.5Hz), 3.80-3.50(2H,m), 3.50-2.70(5H,m), 3.10(1.2H,s), 2.94(1.8H,s) and 1.80-1.20(4H,m)ppm. FAB Mass spectmm, m/z = 542 (M+l). Anal, calc'd for C30H31N5O3 0.25H20, 1.95TFA; C, 52.98; H, 4.49; N, 9.11. Found: C, 53.00; H, 4.37; N, 9.36. EXAMPLE 41 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S)-{N'-acetyl-N'- naphth- 1 -ylmethyl-aminomethyl } -pyrrolidine The title compound was prepared using the protocol described in Example 40 step G using acetyl chloride instead of methane sulfonyl chloride. iH NMR(CD30D, 400 MHz) δ 9.0-8.8(lH,m), 8.20-7.0(12H,m), 5.60- 4.70(4H,m), 4.60-4.10(lH,m), 4.00-3.00(4H,m) and 2.30- 1.80(7H,m)ppm. F.AB Mass spectrum, m/z = 506 (M+l). Anal, calc'd for C31H31N5O2 0.05H20, 1.80TFA; C, 58.39; H, 4.66; N, 9.84. Found: C, 58.40; H, 4.67; N, 9.91. EXAMPLE 42 N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -2(S)-£1 (R)- 1 -(3- chlorophenyP- 1 -hvdroxylmethylpyrrolidine hydrochloride Step A: N- { t-Butoxycarbonyl }-2(S)-[ 1 -(R,S)- 1 -(3-chlorophenyl)- 1 - hydroxyl-methylpyrrolidine To magnesium turnings (753mg, 30.99mmol) in diethylether (1 ml) was added a solution of 3-bromochlorobenzene 3.60ml , 30.88mmol) in diethylether (25 ml) at a rate so as to maintain a gentle reflux.The reaction was heated at reflux for a further 30min, allowed to cool to room temperature and diluted with diethyl ether to a total volume of 37ml. A solution of N-t-butoxycarbonylprolinal (2.50g, 11.61mmol) in diethylether was cooled to 0°C and 3-chloromagnesium bromide solution (17.0 ml, 14.1 mmol) was added. The reaction was stirred at 0°C for 10 min and then allowed to warm to room temperature and stirring continued for 30mins. The solution was cooled to 0°C and quenched by the addition of a saturated ammonium chloride solution (50ml). The mixture was extracted with diethyl ether and the combined extracts were washed with brine, dried (MgSθ4) and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 10-20% ethylacetate in hexanes, gradient elution) to afford the title compounds as an oil. iH NMR(CD3θD, 400 MHz) δ 7.50-7.00(4H, m), 5.95(0.66H, s), 5.55(0.33H, s), 4.85(0.33H, s), 4.50(0.66H, m), 4.30(0.33H, s), 4.06(0.66H, m), 3.70-3.20( 2H, m), 2.00-1.60(13H, m)ppm. Step B: N-{t-Butoxycarbonyl}-2(S)-[(l(S)-l-(3-chlorophenyl)-l(2- picolinoyloxy)]-methylpyrrolidine and N-{t- Butoxycarbonyl}-2(S)-[(l(R)-l-(3-cWorophenyl)-l(2- picolinoyloxy)l-methylpyrrolidine To a solution of the alcohols from step A(105mg, 0.337 mmol), triethylamine (0.235ml, 1.69 mmol), and DMAP (5mg, 0.04 mmol), in methylene chloride( 3.0ml), was added picolinoyl chloride hydrochloride (90mg, 0.51 mmol)and the mixture was stirred 16hr. The reaction was diluted with methylene chloride and washed with saturated NaHCθ3 solution. The organic extracts were dried, (Na2Sθ4) and the solvent evaporated in vacuo. The diastereomeric products were separated by chromatography (Siθ2, 25% ethylacetate in hexanes). First diastereomer eluted:N-{t-Butoxycarbonyl}-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -(2-picolinoyloxy)]-methylpyrrolidine. iH NMR (CD3OD, 400 MHz) δ 8.75(1H, m), 8.26(1H, d, J=0.9Hz), 8.05(1H, dt, J=6.0, and 1.8Hz), 7.68(1H, m), 7.60-7.20(4H, m), 6.60(1H, m), 4.29(1H, s), 3.44(1H, m), 3.25(1H, m), 2.30-2.00(2H, m)ppm. Second diastereomer eluted: N- { t-Butoxycarbonyl } -2(S)- [ 1 (S)- 1 -(3-chlorophenyl)- 1 -picolinoyloxy}- methylpyrrolidine. iH NMR (CD3OD, 400 MHz) δ 8.72(1H, m), 8.25QH, m), 8.05(1H, m), 7.64(1H, m), 7.50(1H, m), 7.50-7.20(3H, m), 6.20-6.05(lH, m), 4.39(1H, s), 3.38QH, q, J=8.2Hz), 3.12(1H, m) and 2.20-1.30Q3H, m)ppm. Step C: N- { t-Butoxycarbonyl }-2(S)-[ 1 (R)- 1 -(3-chlorophenyl)- 1 - hydroxylmethylpyrrolidine To a solution of N-{t-Butoxycarbonyl}-2(S)-[l(R)-l-(3- chlorophenyl)-l-(2-picolinoyloxy)]-methylpyrrolidine (32.7mg, 0.078 mmol), in THF (2.0 ml) was added lithium hydroxide (0.63ml of a l.OM aqueous solution, 0.63mmol) at room temperature and the reaction was stirred for 16hrs. The mixture was diluted with ethylacetate and washed with water and brine, dried (Na2S04), and the solvents evaporated in vacuo. The residue was purified by chromatography (Siθ2, 5% EtOAc in CH2CI2) to afford the product as a white solid. iH NMR(CDCl3, 400 MHz) δ 7.50-7.10(4H, m), 5.57(0.8H, s), 5.15(0.2H, s), 4.85(1H, s), 4.30(0.8H, s), 4.00(0.2H, s), 3.60(0.2H, s), 3.35(0.8H, s), 2.85(0.8H, s), 2.30(0.2H, s), 2.10-1.60(4H, s), 1.56(1.8H, s), and 1.52(7.2H, s) ppm. Step D: N- { t-Butoxycarbonyl }-2(S)- [ 1 (S)- 1 -(3-chlorophenyl)- 1 - hydroxyl-methylpyrrolidine The title compound was prepared using the procedure in step C and N-{t-Butoxycarbonyl}-2(S)-[l(S)-l-(3-chlorophenyl)-l-(2- picolinoyloxy)] -methylpyrrolidine. iH NMR(CDCl3, 400 MHz) δ 7.50-7.10(4H, m), 6.00(1H, s), 4.50(1H, s), 4.06(1H, m), 3.48(1H, m), 3.36(1H, m) and 1.85-1.40(13H, m) ppm. Step E: 2(S)-[l(R)-l-(3-chlorophenyl)-l-hydroxy]- methylpyrrolidine The title compound was prepared by the procedure described in Example 1 step G using the material prepared in step C. iH NMR (CD3OD, 400 MHz) δ 7.47(1H, m), 7.42-7.30(3H, m), 5.07(1H, d, J=3.9Hz), 3.83(1H, m), 3.40-3.20(2H, m), 2.15-1.85(3H, m) and 1.70(1H, m) ppm. Step F: l-Trityl-4-(4-cyanobenzyl)-imidazole To a suspension of activated zinc dust (3.57g, 54.98 mmol) in THF (50ml)was added dibromoethane (0.315ml, 3.60mmol) and the reaction stirred under argon at 20°C. The suspension was cooled to 0°C and α-bromo-p-tolunitrile (9.33g, 47.6 mmol) in THF (100ml) was added dropwise over a period of 10 min. The reaction was then allowed to stir at 20°C for 6hr. Bis(triphenylphosphine) Nickel II chloride (2.40g, 3.64mmol) and 5-iodotrityl imidazole (15.95g, 36.6mmol) was added in one portion.The resulting mixture was stirred 16hr at 20°C and then quenched by addition of saturated NH4CI solution (100ml) and the mixture stirred for 2 hours. Saturated NaHCθ3 solution was added to give a pH of 8 and the solution was extracted with EtOAc ( 2x250ml), dried (MgS04) and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 0-20% EtOAc/CH2Cl2) to afford the title compound as a white solid. iH NMR CDCI3 δ (7.54 (2H, d, J=7.9Hz), 7.38(1H, s), 7.36-7.29 (11H, m), 7.15-7.09(6H, m), 6.58(1H, s) and 3.93(2H, s)ppm. Step G: 5-(4-Cyanobenzyl)-imidazol- 1 -yl-methylacetate To a solution of methyl glycolate (0.545ml, 7.06 mmol), diisopropylethylamine (1.30ml, 7.46 mmol), in CH2CI2 at -78°C was added dropwise trifluoromethanesulfonyl anhydride (1.20ml, 7.13mmol) and the resulting mixture was stirred at -78°C for lhr. A solution of 1- trityl-4-(4-cyanobenzyl)-imidazole (3.00 g, 7.05 mmol) in CH2CI2 (20ml) was cooled to -78°C and added dropwise to the above solution. The cooling bath was removed and the reaction was allowed to warm to room temperature and stirred for 3 hours, and then the solvent was evaporated in vacuo. The residue was dissolved in methanol (60ml), heated at refux for 30 min, cooled and the solvent evaporated in vacuo. The residue was partitioned between saturated NaHCθ3 solution and EtOAc. The organic extracts were dried (Na2Sθ4 and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 3 to 10% MeOH in CH2CI2 , gradient elution) and the title compound was obtained as a white solid. iH NMR δ CDCI3 (7.61 (2H, d, J=7.9Hz), 7.53(1H, s), 7.27(2H, d, J=7.9Hz), 6.89(1H, s), 4.47(2H, s), 3.98(2H, s) and 3.66(3H, s)ppm. Step H: 5-(4-Cyanobenzyl)-imidazol- 1 -yl-acetic acid The title compound was prepared using the procedure described in Example 1 step D using the methyl ester from step G. iH NMR CDC13 δ 8.76(1H, s), 7.71 (2H, d, J=8.0Hz), 7.56(1H, s), 7.45(2H, d, J=8.0Hz), 7.15(1H, s), 4.72(2H, s) and 4.15(2H, s) ppm. Step I: N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -2(S)- [ 1 (R)- 1 -(3-chlorophenyl)- 1 -hydroxy]methylpyrrolidine- hydrochloride To a solution of the acid from step H (135mg, 0.476mmol), the amine hydrochloride salt from step G (lOlmg, 0.477mmol), HOOBT (95mg, 0.58mmol), and triethylamine (0.16ml, 1.15mmol) in DMF (10ml) was added EDC (109mg, 0,569 mmol). The reaction was stirred at room temperature for 48hrs, diluted with EtOAc and the organic layer washed with sat. aq NaHC03, brine, dried (Na2S04) and evaporated in vacuo. The residue was chromatographed (Siθ2, 7% MeOH in CH2CI2) to afford the desired amide which was converted to the corresponding hydrochloride salt by treatment with 1 equivalent of hydrochloric acid in aqueous acetonitrile and evaporation of the solvents in vacuo. iH NMR(CD3θD, 400 MHz) δ 8.85-8.75(lH, m), 7.90-7.10(9H, m), 5.40-5.00(3H, m), 4.40-4.00(3H, m), 3.60-3.00(2H, m) and 2.30-1.20(4H, m)ppm. FAB Mass spectmm, m/z = 435 (M+l). Anal, calc'd for C24H23N4O2CI 1.00 HCl, 0.45 H2O; C, 60.12; H, 5.23; N, 11.68; Found: C, 60.08; H, 5.09; N, 11.77. EXAMPLE 43 N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl }-2(S)-[l (S)- 1-(3- chlorophenyl)- 1 -hvdroxylmethylpyrrolidine Step A: 2(S)-[l(S)-l-(3-chloroρhenyl)-l-hydroxy] methylpyrrolidine hydrochloride The title compound was prepared by the procedure described in Example 1 step G using the material prepared in Example 42 step D. lH NMR(CD30D, 400 MHz) δ 7.52(1H, m), 7.50-7.32(3H, m),4.75(lH, d, J=6.9Hz), 3.71(1H, q, J=8.0Hz), 3.40-3.20(2H, m) and 2.20-1.80(4H, m)ppm. Step B: N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)acetyl}-2(S)-[l(S)- 1 -(3-chlorophenyP- 1 -hvdroxylmethylpyrrolidine The title compound was prepared by the procedure described in Example 42 step I using the amine hydrochloride from step A. iH NMR(CD30D, 400 MHz) δ 9.00-8.90(lH, m), 7.90-7.10(9H, m), 5.75(1H, d, J=17.0Hz), 5.30(1H, d, J=17.0Hz), 5.17(1H, q, J=18Hz), 4.46(1H, d, J=9.5Hz), 4.40-4.00(3H, m), 3.60-3.20(2H, m), 2.20-1.20(4H, m)ppm. FAB Mass spectmm, m/z = 435 (M+l). Anal, calc'd for C24H23N4O2CI 1.00 HCl, 0.55 H2O; C, 59.89; H, 5.26; N, 11.64. Found: C, 59.86; H, 5.22; N, 12.00. EXAMPLE 44 N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(R)-l-(3- chlorophenyP- 1 -hvdroxylmethylpyrrolidine Step A: l-Hydroxyethyl-5-(4-Cyanobenzyl)-imidazole A solution of 5-(4-cyanobenzyl)-imidazol-l-yl- methylacetate (0.113 g, 0.472 mmol) in methanol (2ml) at 0°C was treated with sodium borohydride (80.7mg, 2.1mmol). After 1 hr the reaction was quenched by addition of saturated NH4CI solution (2ml). Saturated NaHCθ3 was added and the mixture extracted with ethyl acetate (3x25ml), dried (MgS04) and the solvent evaporated in vacuo. The title compound was isolated by chromatography (Siθ2, 10%MeOH in CH2CI2) as a white solid. iH NMR CDC13 δ 7.61 (2H, d, J=7.9Hz), 7.55(1H, s), 7.27(2H, d, J=7.9Hz), 6.83(1H, s), 4.05(2H, s), 3.87(2H, t, J=5.1Hz) and 3.74(2H, t, J=5.1Hz)ppm. Step B: 5-(4-Cvanobenzyl)-imidazol- 1 -yl-ethyl methanesulfonate A solution of l-hydroxyethyl-5-(4-Cyanobenzyl)-imidazole (0.532 g, 2.34 mmol) in methylene chloride (70ml) at 0°C was treated with Hunigs base (0.489ml, 2.81 mmol) and methanesulfonyl chloride (0.219ml, 2.81 mmol). After 2 hrs the reaction was quenched by addition of saturated NaHC03 solution (50ml) and the mixture extracted with methylene chloride (50ml), dried (MgS04) and the solvent evaporated in vacuo. The title compound was used without furthur purification. iH NMR CDC13 δ 7.62 (2H, d, J=7.9Hz), 7.54(1H, s), 7.29(2H, d, J=7.9Hz), 6.87(1H, s), 4.25(2H, t), 4.10-4.00(4H, m), 3.74(2H, t, J=5.1Hz) and 2.90(3H, s)ppm. Step C: N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(R)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine To a solution of 5-(4-cyanobenzyl)-imidazol- l-yl)ethyl methanesulfonate (290 mg, 0.95 mmol) in DMF (10ml) was added the amine (200mg, 0.945 mmol) (prepared by treatment of the amine hydrochloride salt obtained in Example 42 step E with IM sodium hydroxide extraction into EtOAc, drying (Na2S04), and evaporation of solvent), sodium iodide (710mg, 4.74 mmol) and Hunig's base (0.330ml, 1.89 mmol). The mixture was stirred at 55°C for 12 hrs, and the solvent evaporated in vacuo. The residue was treated with water and IM NaOH to a pH of 11 and extracted into EtOAc. The organic extracts were dried (Na2S04), and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 1-2% saturated ammonia in acetonitrile, gradient elution. The residue was converted to the corresponding hydrochloride salt by treatment with 1 equivalent of hydrochloric acid in aqueous acetonitrile and evaporation of the solvents in vacuo.. FAB Mass spectmm, m/z = 421 (M+l). Anal, calc'd for C24H25N4OCI 2.00HC1, O.6OH2O; C, 57.12 H, 5.63; N, 11.10. Found: C, 57.08; H, 5.71; N, 11.24. EXAMPLE 45 N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(S)-l-(3- chlorophenyP- 1 -hvdroxylmethylpyrrolidine The title compound was prepared using the procedure described in Example 44 using the amine hydrochloride from Example 43 step A. FAB Mass spectmm, m/z = 421 (M+l). Anal, calc'd for C24H25N4OCI 2.00 HCl, 0.20 H2θ; C, 57.95; H, 5.55; N, 11.26. Found: C, 57.95; H, 5.37; N, 11.30. EXAMPLE 46 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-Il(R)-l-(3- chlorophenyP- 1 -hvdroxylmethylpyrrolidine Step A: l-Triphenylmethyl-4-(hydroxymethyl)-imidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35.0 g, 260 mmol) in dry DMF (250 ml) at room temperature was added triethylamine (90.6 ml, 650 mmol). A white solid precipitated from the solution. Chlorotriphenylmethane (76.1 g, 273 mmol) in of DMF (500 ml) was added dropwise. The reaction mixture was stirred for 20 hrs, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid which was sufficiently pure for use in the next step. Step B: l-Triphenylmethyl-4-(acetoxymethyl)-imidazole The alcohol from Step A (260 mmol, prepared above) was suspended in pyridine (500 ml). Acetic anhydride (74 ml, 780 mmol) was added dropwise, and the reaction was stirred for 48 hrs during which it became homogeneous. The solution was poured into EtOAc, washed sequentially with water, 5% aqueous HCl solution, saturated aqueous NaHCθ3, solution, and brine, the organic extracts were dried (Na2Sθ4), and concentrated in vacuo to provide the product as a white powder, which was sufficiently pure for use in the next reaction. Step C: 1 -(4-Cyanobenzyl)-5-(acetoxymethyl)-imidazole hydrobromide A solution of the product from Step B (85.8 g, 225 mmol) and 4-cyano benzyl bromide (50.1 g, 232 mmol) in EtOAc (500ml) was stirred at 60 °C for 20 hrs, during which a pale yellow precipitate formed. The reaction was cooled to room temperature and filtered to provide the solid imidazolium bromide salt. The filtrate was concentrated in vacuo to a volume (200 ml), reheated at 60 °C for 2 hrs, cooled to room temperature, and filtered again. The filtrate was concentrated in vacuo to a volume (100 m), reheated at 60 °C for another 2hrs, cooled to room temperature, and concentrated in vacuo to provide a pale yellow solid. All of the solid material was combined, dissolved in methanol (500ml), and warmed to 60 °C. After 2hrs, the solution was concentrated in vacuo to provide a white solid which was triturated with hexane to remove soluble materials. Removal of residual solvents in vacuo provided the titled product hydrobromide as a white solid which was used in the next step without further purification. Step D: l-(4-Cvanobenzyl)-5-(hvdroxymethvP-imidazole To a solution of the acetate from Step C (50.4 g, 150 mmol) in 3: 1 THF/water (1.5 1) at 0 °C was added lithium hydroxide monohydrate (18.9 g, 450 mmol). After lhr, the reaction was concentrated in vacuo, diluted with EtOAc (3 1), and washed with water, sat. aq. NaHCθ3 and brine. The solution was then dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the cmde product as a pale yellow fluffy solid which was sufficiently pure for use in the next step without further purification. Step E: l-(4-CvanobenzvP-5-(chloromethyl)-imidazole A solution of l-(4-Cyanobenzyl)-5-(hydroxymethyl)- imidazole (l.Og, 4.70mmol), in thionyl chloride (5ml), was stirred at 70°C for 16hrs. The solvent was evaporated in vacuo and the resulting solid suspended in CH2CI2, collected by filtration and dried in vacuo. The material was sufficiently pure to be used without furthur purification. iH NMR CD3OD δ 9.06 (IH, s), 7.83(2H, d, J=8.0Hz), 7.77(1H, s), 7.55(2H, d, J=8.0Hz), 5.67(2H, s) and 4.78(2H, s) ppm. Step F : N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)- 1 (R)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine A solution of the chloride from step E (127 mg, 0.474 mmol) in DMF (2 ml) was added 2(S)-[l(R)-l-(3-chlorophenyl)-l- hydroxy]methylpyrrolidine (prepared by treatment of the amine hydrochloride salt obtained in Example 42 step E with IM sodium hydroxide and extraction into EtOAc, drying (Na2S04) and evaporation of solvent), ( lOOmg, 0.472mmol) and Hunig's base (0.20ml, 1.15mmol). The mixture was stirred at room temperature for 12 hrs. The reaction was diluted with EtOAc and the pH adjusted to 11 by the addition of IM NaOH. The organic extracts were dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, eluting with 3% saturated ammonia/acetonitrile). The residue was converted to the corresponding hydrochloride salt by treatment with 2 equivalents of hydrochloric acid in aqueous acetonitrile and evaporation of the solvents in vacuo. FAB Mass spectmm, m/z = 407 (M+l). Anal, calc'd for C23H23N4OCI 2.00 HCl, 0.65 H2O; C, 56.51; H, 5.36; N, 11.46. Found: C, 56.57; H, 5.36; N, 11.35. EXAMPLE 47 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-£l(S)-l-(3- chlorophenyP- 1 -hydroxylmethylpyrrolidine The title compound was prepared using the procedure described in Example 46 using the amine hydrochloride from Example 43 step A. FAB Mass spectmm, m/z = 407 (M+l). Anal, calc'd for C23H23N4OCI 2.00 HCl, 0.65 H2O; C, 56.20; H, 5.39; N, 11.40. Found: C, 56.25; H, 5.33; N, 11.30. EXAMPLE 48 N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl }-4(R)-hydroxy-2(S)- ri(R)-l-(3-chlorophenyl)-l-hvdroxylmethylpyrrolidine hvdochloride The title compound was prepared as in Example 42 steps A-I using 4(R)- t-butyldimethylsiloxy-prolinal. iH NMR CD3OD δ 8.85 (IH, s), 7.74(2H, d, J=8.3Hz), 7.50(2H, d, J=8.3Hz), 7.50-7.20(5H, m), 5.39(1H, m), 5.24(1H, d, J=17.1Hz), 5.05(1H, d, J=17.1Hz), 4.55(1H, m), 4.30(1H, m), 3.65(1H, dd, J=11.0 and 4.2Hz), 3.50(1H, d, J=11.0Hz), 3.40-3.00(2H, m), 2.14(1H, m) and 1.50(lH, m)ppm. FAB Mass spectmm, m/z = 451 (M+l). EXAMPLE 49 N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -4(R)-hydroxy-2(S)- [ 1 (S)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine The title compound was prepared as in Example 43 using 4(R)-hydroxy-2(S)-[l(S)-l-(3-chlorophenyl)-l- hydroxy]methylpyrrolidine. Anal, calc'd for C24H23N4O3CI 1.00 HCl, 0.15 NH4CI; C, 58.19; H, 5.01; N, 11.73. Found: C, 58.09; H, 5.33; N, 11.97. EXAMPLE 50 N-{ l-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl}-4(R)-hydroxy-2(S)-[i(R} 1 -(3-chlorophenvP- 1 -hydroxylmethylpyrrolidine To a solution of 4(R)-hydroxy-2(S)-[l(R)-l-(3-chlorophenyl)-l- hydroxyjmethylpyrrolidine (181mg, 0.79mmol), Hunigs base (0.138ml, 0.79mmol) and l-(4-cyanobenzyl)-imidazol-5-yl) ethylmethanesulfonate (263mg, 0.79 mmol) in DMF (1.6ml) was added sodium iodide (594mg, 3.96 mmol) and the mixture heated at 55°C for 16hrs. The reaction was diluted withEtOAc and the pH adjusted to 12 with IM NaOH. The organic extract was washed with brine, dried (MgSθ4), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 2 to 5% NH4OH in acetonitrile, gradient elution) to afford the title compound which was converted to an HCl salt. Anal, calc'd for C24H25N4O2CI 2.00 HCl, 0.85 H2O; C, 54.89; H, 5.51; N, 10.67. Found: C, 54.85; H, 5.43; N, 10.74. FAB Mass spectmm, m/z = 437 (M+l). EXAMPLE 51 N-{ l-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl}-4(R)-hydroxy-2(S)-[l(S)- 1 -(3-chlorophenvP- 1 -hydroxylmethylpyrrolidine The title compound was prepared according to the procedure described in Example 50 using 4(R)-hydroxy-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine. Anal, calc'd for C24H25N4O2CI 2.00 HCl, 0.60 H2O, 0.35 EtOAc; C, 55.32; H, 5.67; N, 10.16. Found: C, 55.33; H, 5.75; N, 9.95. FAB Mass spectmm, m/z = 437 (M+l). EXAMPLE 52 N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl]-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine The title compound was prepared according to the procedure described in Example 44 step C using 4(R)-hydroxy-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine. Anal, calc'd for C24H25N4O2CI 2.00 HCl, 0.70 H2O; C, 55.17; H, 5.48; N, 10.72. Found: C, 55.20; H, 5.43; N, 10.63. FAB Mass spectmm, m/z = 437 (M+l). EXAMPLE 53 N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl]-4(R)-hydroxy-2(S)-[l(S)- 1 -(3-chlorophenvP- 1 -hydroxylmethylpyrrolidine The title compound was prepared according to the procedure described in Example 52 using 4(R)-hydroxy-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine Anal, calc'd for C24H25N4O2CI 2.00 HCl, 0.95 H2O; C, 54.70; H, 5.53; N, 10.63. Found: C, 54.75; H, 5.45; N, 10.55. FAB Mass spectmm, m/z = 437 (M+l). EXAMPLE 54 N-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl]-4(R)-hydroxy-2(S)- r 1 (S)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine The title compound was prepared according to the procedure described in Example 46 step F using 4(R)-hydroxy-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine. Anal, calc'd for C23H23N4O2CI 2.00 HCl, 0.80 H2O; C, 54.14; H, 5.25; N, 10.98. Found: C, 54.09; H, 5.30; N, 11.37. FAB Mass spectmm, m/z = 423 (M+l). EXAMPLE 55 N-[l-(4-Cyanobenzyl)-l-imidazol-5-ylmethyl]-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyP- 1 -hydroxylmethylpyrrolidine The title compound was prepared according to the procedure described in Example 46 step F using 4(R)-hydroxy-2(S)-[(3- chlorophenyl)-(R)-hydroxymethyl]-pyrollidine. Anal, calc'd for C23H23N402C1 2.00 HCl, 0.80 H2O;, C, 54.14; H, 5.25; N, 10.98. Found: C, 54.13; H, 5.40; N, 11.09. FAB Mass spectmm, m/z = 423 (M+l). EXAMPLE 56 N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl 1 aminomethylpyrrolidine Step A: 4(R)-Hvdroxyproline methyl ester A suspension of 4(R)-hydroxyproline (35.12g, 267.8mmol) in methanol (500ml) was saturated with gasseous hydrochloric acid. The resulting solution was allowed to stand for 16hrs and the solvent evaporated in vacuo to afford the title compound as a white solid. iH NMR CD3OD δ 4.60 (2H, m), 3.86(3H, s), 3.48(1H, dd, J=3.6 and 12.0Hz), 3.23(1H, d, J=12.0Hz), 2.43(1H, m) and 2.21(1H, m) ppm. Step B: N-t-Butoxycarbonyl-4(R)-hydroxyproline methyl ester To a solution of 4(R)-hydroxyproline methyl ester (53.5g, 268mmol), and triethylamine (75ml, 540mmol), in CH2CI2 (500ml), at 0°C, was added a solution of di-t-butyl dicarbonate (58.48, 268mmol), in CH2CI2 (75ml). The resulting mixture was stirred for 48hrs at room temperature. The solution was washed with 10% aqueous citric acid solution, saturated NaHC03 solution, dried (Na2Sθ4) and the solvent evaporated in vacuo. The title compound was obtained as a yellow oil and used in the next step without furthur purification. lH NMR CD3OD δ 4.40-4.30 (2H, m), 3.75(3H, m), 3.60-3.40(2H, m), 2.30(1H, m), 2.05(1H, m) and 1.55-1.40(9H, m) ppm. Step C: N-t-Butoxycarbonyl-4(R)-t-butyldimethylsilyloxy proline methyl ester To a solution of N-t-butoxycarbonyl-4(R)-hydroxy proline methyl ester (65.87g, 268mmol), and triethylamine (41ml, 294mmol), in CH2CI2 (536ml), at 0°C, was added a solution of t-butyldimethyl silylchloide (42.49g, 282mmol), in CH2CI2 (86ml). The resulting mixture was stirred for 16hrs at room temperature. The solution was washed with 10% aqueous citric acid solution, saturated NaHCθ3 solution, dried (Na2S04) and the solvent evaporated in vacuo. The title compound was obtained as a yellow oil and used in the next step without furthur purification. iH NMR CD3OD δ 4.60-4.40 (2H, m), 3.75(3H, m), 3.60-3.20(2H, m), 2.30-1.90(2H, m), 1.45-1.40(9H, m), 0.90-0.85(9H, m), 0.10-0.00(6H, m) ppm. Step D: N-t-Butoxycarbonyl-4(R)-t-butyldimethylsilyloxy-2(S)- hydroxymethylpyrrolidine A solution of N-t-butoxycarbonyl-4-(R)-t- butyldimethylsilyloxy proline methyl ester (86.65g, 241mmol), in THF (150ml), was added over 90 minutes to a solution of lithium aluminum hydride (247ml of a IM solution in THF, 247mmol), under argon, so that the temperature did not exceed 12°C. Stirring was continued for 50 mins and then EtOAc (500ml) was added cautiously, followed by sodium sulphate decahydrate (34g), and the resulting mixture stirred for 16 hrs at room temperature. Anhydrous sodium sulphate (34g) was added and the mixture stirred an additional 30 min and then filtered. The solids were washed with EtOAc (800ml), the filtrates combined and the solvent evaporated in vacuo. The title compound was obtained as a colourless oil and used in the next step without further purification. Step E: N-t-Butoxycarbonyl-4(R)-t-butyldimethylsilyloxy-2(S)- methanesulfonyloxymethylpyrrolidine The title compound was prepared according to the procedure described in Example 40 step B using N-t-butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)-hydroxymethylpyrrolidine. FAB Mass spectmm, m/z = 410(M+1). *H NMR CDC13 δ 4.60-4.00 (4H, m), 3.60-3.30(2H, m), 2.98(3H, s), 2.05-2.00(2H, m), 1.48-1.42(9H, m),0.90-0.80(9H, m), 0.10-0.00(6H, m) ppm. Step F: Preparation of N-t-Butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)-azidomethylpyrrolidine In a flask protected by a safety screen, a solution of N-t- butoxycarbonyl-4(S)-t-butyldimethylsilyloxy-2(S)-methanesulfonyloxy methyl pyrroUdine(10.40g, 25.39mmol) and tetrabutylammonium azide (8.18g, 28.7mmol) in toluene (250ml) was stirred at 80°C for 5hr. The reaction was cooled to room temperature and diluted with EtOAc (250ml), washed with water and brine and dried (Na2Sθ4). The solvent was evaporated in vacuo to afford the title compound as a yellow oil which was used in the next step without furthur purification. iH NMR CDCI3 δ 4.60-3.20 (6H, m), 2.05-1.90(2H, m), 1.47(9H, s), 0.87(9H, s) and 0.10-0.00(6H, m) ppm. Step G: Preparation of N-t-Butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)-aminomethylpyrrolidine A solution of N-t-butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)-azidomethylpyrrolidine (9.06g, 25.39mmol) in EtOAc (120ml) was purged with argon and 10% palladium on carbon (1.05g) added. The flask was evacuated and stirred under an atmosphere of hydrogen (49 psi) for 16hrs. The hydrogen was replaced by argon, the catalyst removed by filtration and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 2.5 to 5% saturated NH4OH in acetonitrile, gradient elution), to afford the title compound as an oil. iH NMR(CDCl3, 400 MHz) δ 4.40-2.60 (6H, s), 2.05-1.80(2H, m), 1.46(9H, s), 1.36(2H, s), 0.87(9H, s), 0.10-0.00(6H, m)ppm. Step H: Preparation of N-t-Butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)- { N'-3- chlorobenzyl } aminomethylpyrrolidine To a slurry of 3-chlorobenzaldehyde (1.2ml, 10.6mmol), cmshed 3 A molecular sieves (9.5g) and the amine from step G (3.50g, 10.6mmol) in methanol (150 ml) was added sodium cyanoborohydride (11.0ml of a IM solution in THF, 1 l.Ommol) at room temperature. The pH was adjusted to 7 by the addition of glacial acetic acid (0.68ml, 12mmol) and the reaction was stirred for 16 hrs. The reaction was filtered and the filtrate evaporated in vacuo. The residue was partitioned between EtOAc and saturated NaHCθ3 solution and the organic extract washed with brine, dried (Na2S04), and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 2.5% MeOH in CH2CI2) to provide the title compound as an oil. 1HNMR(CDC13, 400 MHz) δ 7.40-7.10(4H, m), 4.36(1H, s), 4.15- 3.90(2H, m), 3.90-3.30(2H, m), 2.85-2.60(2H, m), 2.05-1.90(2H, m), 1.44(9H, s), 0.87(9H, s) and 0.06(6H, m) ppm. Step I: Preparation of N-t-Butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)- { N'-3-chlorobenzyl-N'-acetyl } - aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-4(R)-t- butyldimethylsilyloxy-2(S)- { N'-3-chlorobenzyl } -aminomethyl pyrrolidine (3.80g, 8.35 mmol) in CH2CI2 (85ml) and triethylamine (2.40ml, 17.0 mmol) at 0°C was added acetyl chloride (0.60ml, 8.44 mmol). The reaction was stirred at room temperature for lhr, diluted with water and extracted with CH2CI2. The extracts were washed with brine, dried (Na2S04) and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 10 to 25% EtOAc in CH2CI2, gradient elution). iHNMR (CDC13, 400 MHz) δ 7.40-7.00(4H, m), 5.10-3,00(8H, m), 2.20-1.70(5H, m), 1.50-1.30(9H, m), 0.87(9H, s) and 0.06(6H, m) ppm. Step J: Preparation of N-t-Butoxycarbonyl-4(R)-hydroxy-2(S)- { N' -3-chlorobenzyl-N'-acetyl I -aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-4(R)-t- butyldimethylsilyloxy -2(S)- { N'-3-chlorobenzyl-N'-acetyl } - aminomethylpyrrolidine (4.02g, 8.09 mmol) in THF (80ml) at 0°C was added tetrabutylammonium fluoride (9.00ml of a IM solution in THF. 9.00mmol). The reaction was stirred at 0°C for lhr and then at room temperature for 30min. The reaction was quenched by the addition of a saturated NH4CI solution (50ml), dilution with EtOAc. The organic extracts were washed with brine, dried (Na2Sθ4) and the solvent evaporated in vacuo. The residue purified by chromatography (Siθ2, 3 to 5% MeOH in CH2CI2, gradient elution) to afford the title compound as a foam. 1HNMR (CDCI3, 400 MHz) δ 7.40-7.00(4H, m), 5.00-4,00(4H, m), 4.00-3.10(4H, m), 2.30-1.60(5H, m) and 1.50-1.30(9H, m) ppm. Step K: 4(R)-hydroxy-2(S)- { N * -3-chlorobenzyl-N'-acetyl }- aminomethylpyrrolidine hydrochloride The title compound was prepared by the procedure described in Example 1 step G using N-t-butoxycarbonyl-4(R)-hydroxy-2(S)-{N'-3- chlorobenzyl-N'-acetyl } -aminomethylpyrrolidine. iH NMR(CD3θD, 400 MHz) δ 7.50-7.15(4H, m), 4.75(2H, m), 4.52(1H, m), 4.00-3.90(2H, m), 3.45(2H, m), 3.18(1H, brd, J=7.3Hz), 2.20(3H,s), 2.05(1H, m) and 1.85(1H, m) ppm. Step L: 1 -(4-Cyanobenzyl)-5-imidazole carboxaldehyde To a solution of l-(4-Cyanobenzyl)-5-(hydroxymethyl)- imidazole (21.5 g, 101 mmol) in DMSO (500ml) at room temperature was added triethylamine (56 ml, 402 mmol), then Sθ3-pyridine complex (40.5 g, 254 mmol). After 45 min, the reaction was poured into EtOAc, washed with water and brine, dried (Na2S04), and concentrated in vacuo to provide the aldehyde as a white powder which was sufficiently pure without further purification. Step M: N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl-methyl-4(R)- hydroxy-2(S)- { N'-3-chlorobenzyl-N'-acetyl } - aminomethylpyrrolidine To a slurry of l-(4-Cyanobenzyl)-5-imidazole carboxaldehyde (165mg, 0.781 mmol), crashed 3A molecular sieves (0.78g), and the amine hydrochloride from step K (0.235mg, 0.66mmol) in methanol (10 ml) was added sodium cyanoborohydride (0.80ml of a IM solution in THF, 0.80mmol) at room temperature. The reaction was stirred for 16 hrs, filtered and the filtrate evaporated in vacuo. The residue was partitioned between EtOAc and saturated NaHCθ3 solution and the organic extract washed with brine, dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 5% NH4OH in acetonitrile) to provide the title compound as a foam. Anal, calc'd for C26H28N5O2CI I.OOH2O: C, 62.96; H, 6.10; N, 14.12. Found: C, 62.96; H, 5.78; N, 14.02. FAB HRMS exact mass calc'd for C26H29N5O2CI 478.200978(MH+), found 478.200698 EXAMPLE 57 N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl } -4(R)-hydroxy-2(S)- { N - acetyl-N'-3-chlorobenzyl 1 aminomethylpyrrolidine The title compound was prepared using the procedure described in Example 1 stepH, and 4(R)-hydroxy-2(S)-{N'-acetyl-N'-3- chlorobenzyl } -aminomethypyrrolidine hydrochloride. Anal, calc'd for C27H28N5O3CI 1.0-HCl, 1.15 H2O: C, 61.57; H, 5.80; N, 13.30. Found: C, 61.60; H, 5.47; N, 13.21. FAB HRMS exact mass calc'd for C26H29N5O2CI 506.195893(MH+), found 506.197103. EXAMPLE 58 N { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine Step A: N-t-Butoxycarbonyl-4(R)-methoxy-2(S)-{N'-acetyl-N' -3- chlorobenzyl } aminomethylpyrrolidine To a solution of N-t-Butoxycarbonyl-4(S)-hydroxy -2(S)- {N'-acetyl-N' 3-chlorobenzyl} aminomethylpyrrolidine (928mg, 2.42 mmol) in DMF (12ml) at 0°C was added sodium hydride (145mg of a 60% dispersion in mineral oil, 3.63mmol). ter 15 min methyl iodide (0.30ml, 4,82mmol), was added and the reaction stirred at room temperature for 16 hrs. The reaction was quenched with saturated NaHCθ3 solution (2ml) and extracted with ethyl acetate. The orgainic extract was washed with brine and dried (Na2S04, and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, 25 to 50% EtOAc in CH2CI2, gradient elution) to afford the title compound as a foam. iH NMR(CD3θD, 400 MHz) δ 7.50-7.10(4H, m), 4.90-4.05(4H, m), 3.95(1H, m), 3.90-3.30(3H, m), 3.30(3H, s), 2.10-1.70(5H, s) and 1.60- 1.30(9H, m) ppm. Step B: 4(S)-Methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } - aminomethylpyrrolidine hydrochloride The title compound was prepared by the procedure described in Example 1 step G using N-t-butoxycarbonyl-4(S)-methoxy- 2(S)- { N'-acetyl-N'-3-chlorobenzyl- } aminomethylpyrrolidine. iH NMR(CD30D, 400 MHz) δ 7.40(1H, t, J=7.7Hz), 7.35(1H, d, J=9.2Hz), 7.29(1H, s), 7.20(1H, d, J=7.7Hz), 4.73(1H, d, J=17.0Hz), 4.68(1H, d, J=17.0Hz), 4.10(1H, m), 3.96(1H, m), 3.81(1H, m), 3.50- 3.37(2H, m), 3.32-3.30(4H, m), 2.30-2.24(lH, m), 2.18(3H, s) and 1.75(lH, m)ppm. Step C: N{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl-methyl-4(R)- hydroxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compound was prepared by the procedure described in Example 56 step M using l-(4-Cyanobenzyl)-5-imidazole carboxaldehyde and the amine hydrochloride from step B. Anal, calc'd for C27H30N5O2CI 2.25HC1, 1.6OH2O: C, 53.79; H, 5.93N, 11.62. Found: C, 53.79; H, 5.92; N, 11.39. FAB HRMS exact mass calc'd for C27H31N5O2CI 492.216628(MH+), found 492.216101. EXAMPLE 59 N-{ l-(4-Cyanophenethyl)-lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- ( N'-acetyl-N'-3-chlorobenzyl \ aminomethylpyrrolidine Step A: Preparation of l-(4-Cvanophenyl)ethyl bromide To a solution of l-(4-Cyanophenyl)ethanol l.Olg, 6.84mmol), in diethyl ether (15ml) and triphenylphosphine (2.14g, 8.17 mmol), was added carbon tetrabromide (2.82g, 8.50mmol) in dieathylether (20ml) at room temperature. After 30 min the reaction was filtered through celite and evaporated to dryness. The residue was purified by chromatography (Si02, 5% EtOAc in hexanes) to afford the title compound as an oil iH NMR(CDC13, 400 MHz) δ 7.64(2H, d, J=8.2Hz), 7.53(2H, d, J=8.2Hz), 5.15(1H, q, J=7.0Hz) and 2.03(3H, d, J=7.0Hz) ppm. Step B: l-(4-Cvanophenethyl)-lH-imidazol-5-yl- carboxaldehyde A mixture of 3-tritylimidazol-5yl-carboxaldehyde (805mg, 2.38mmol), and the bromide from step A (0.50g, 2,38mmol), was heated at 60°C for 16 hrs in the presense of tetrabutylammonium iodide (89mg, 0.24mmol) in acetonitrile (10ml). The cooled reaction was diluted with EtOAc and washed with saturated aqueous NaHC03, brine and dried (Na2S04). The solvent was evaporated in vacuo and the residue chromatographed (Siθ2, 5%MeOH in CH2CI2) to afford the title compound. Step C: N-{ l-(4-Cyanophenethyl)-lH-imidazol-5-yl-methyl-4(R)- hydroxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compound was prepared by the procedure described in Example 56 step M using l-(4-Cyanophenethyl)-lH- imidazol-5-yl- carboxaldehyde and 4(R)-methoxy-2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine hydrochloride. FAB HRMS exact mass calc'd for C28H33N5O2CI 506.232278(MH+), found 506.231473. EXAMPLE 60 N { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-acetyl } -4(R)-methoxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compound was prepared according to the procedure described in Example 1 step H using 4(R)-methoxy-2(S)-{N'-acetyl-N'-3- chlorobenzyl} aminomethylpyrrolidine hydrochloride. Anal, calc'd for C28H30N5O2CI 2.00 TFA, 0.50 H2O: C, 50.77; H, 4.39, N, 9.25. Found: C, 50.78; H, 4.38; N, 9.24. FAB HRMS exact mass calc'd for C28H31N5O2CI 520.211543(MH+), found 520.211434. EXAMPLE 61 AND 62 N- { l-(4-Cyanopheneth- 1 -yl)- lH-imidazol-5-yl-acetyl-4(R)-methoxy- 2(S)- ( N'-acetyl-N'-3-chlorobenzyl I aminomethylpyrrolidine Step A: Preparation of (R,S)[l-(4-cyanopheneth-l-yl)-lH-imidazol- 5-yllacetic acid The title compound was prepared according to the procedure in Example 1 steps C and D replacing 4 cyanobenzylbromide with l-(4- cyanophenyl)ethyl bromide. iH NMR CD3OD δ 8.44 (IH, d, J=0.8Hz) 7.73(2H,d, J=8.3Hz), 7.38(2H,d, J=8.3Hz),7.14(lH,s), 5.73(lH,q, J=7.0Hz), 3.55(lH,d, J=17.2Hz), 3.33(lH,d, J=17.2hz) and 1.92(3H,d, J=7.0Hz)ppm. Step B: N-{ l-(4-Cyanophen-(R,S)-ethyl)-lH-imidazpl-5-yl-acetyl- 4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compounds was prepared according to the procedure described in Example 1 step H using 4(S)-Methoxy-2(S)-{N'- acetyl-N'-3-chlorobenzyl} aminomethylpyrrolidine hydrochloride and the acids from step A. Anal, calc'd for C29H32N5O3CI 2.10 TFA, 0.35 H2O: C, 51.14; H, 4.50, N, 8.98. Found: C, 51.15; H, 4.53; N, 8.99. FAB HRMS exact mass calc'd for C29H33N5O3CI 534.227193(MH+), found 534.226630. and Anal, calc'd for C29H32N5O3CI 1.90 TFA, 0.25 H2O: C, 52.17; H, 4.59, N, 9.27. Found: C, 52.15; H, 4.61; N, 9.19. FAB HRMS exact mass calc'd for C29H33N5O3CI 534.227193(MH+), found 534.228764. EXAMPLE 63 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl-ethyl}-4(R)-methoxy-2(S)-{N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine Step A: Preparation of (l-(4-Cyanobenzyl)-lH-imidazol-5-yl)- ethanol To a stirred solution of the ester from Example 1, step C, (1.50g, 5.88mmol), in methanol (20ml) at 0°C, was added sodium borohydride (l.Og, 26.3mmol) portionwise over 5 minutes. The reaction was stirred at 0°C for 1 hr and then at room temperature for an additional 1 hr. The reaction was quenched by the addition of sat.NH4Cl solution and the methanol was evaporated in vacuo.. The residue was partitioned between EtOAc and sat NaHCθ3 solution and the organic extracts dried (MgSθ4), and evaporated in vacuo.. The residue was purified by chromatography (Siθ2, 4 to 10% methanol in methylene chloride, gradient elution) to afford the title compound as a solid. iH NMR CDC13 δ 7.64(2H, d, J=8.2Hz), 7.57(1H, s), 7.11(2H, d, J=8.2Hz), 6.97(1H, s), 5.23(2H, s), 3.79(2H, t, J=6.2Hz) and 2.66(2H, t, J=6.2Hz) ppm. Step B: l-(4-Cvanobenzyl)-imidazol-5-yl-ethylmethanesulfonate A solution of ( 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl)-ethanol (0.500 g, 2.20 mmol) in methylene chloride (6.0 ml) at 0°C was treated with Hunig's base (0.460ml, 2.64mmol) and methane sulfonyl chloride (0.204ml, 2.64mmol). After 2 hrs, the reaction was quenched by addition of saturated NaHCθ3 solution (50ml) and the mixture was extracted with methylene chloride (50ml), dried (MgS04) and the solvent evaporated in vacuo. The title compound was used without furthur purification. iH NMR CDC13 δ 7.69 (IH, s) 7.66(2H, d, J=8.2Hz), 7.15 (2H, d, J=8.2Hz), 7.04(1H, s), 5.24(2H, s), 4.31(2H, t, J=6.7Hz), 2.96(3H, s), and 2.88(2H, t, J=6.6Hz)ppm. Step C: N{ l-(4-Cyanobenzyl)-lH--imidazol-5-ylethyl}-4(R)- methoxy-2(S)-{ N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine A mixture of 4(R)-methoxy-2(S)-{N'-acetyl-N'-3- chlorobenzyl-aminomethyl} pyrrolidine (135mg, 0.405mmol), the mesylate from step B (114mg, 0.373mmol), potassium carbonate (140mg, l.Olmmol), and sodium iodide (243mg, 1.62mmol) in DMF (1.0ml), were heated at 55°C for 16 hrs. The cooled mixture was diluted with EtOAc, washed with NaHCθ3 solution and brine , dried (Na2S04) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (C-18, 95:5 to 5:95 water in acetonitrile containing 0.1% TFA, gradient elution). The title compound was obtained as a white solid after lyophillisation. Anal. calc'd for C28-H32N5O2CI 3.15 TFA, 0.45 H2O: C, 47.17; H, 4.16, N, 8.02. Found: C, 47.16; H, 4.19; N, 7.99. FAB HRMS exact mass calc'd for C28H33N5O2CI 506.232278(MH+), found 506.231017. EXAMPLE 64 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine The title compound was prepared by the procedure described in Example 63 using 2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine Anal, calc'd for C27H30N5OCI 2.15 HCl, 3.05 H2O: C, 53.22; H, 6.33, N, 11.49. Found: C, 53.23; H, 6.33; N, 11.29. EXAMPLE 65 N { 1 -(4-Cyanophenethyl)- lH-imidazol-5-yl-ethyl } -4(R)-methoxy-2(S)- ( N'-acetyl-N'-3-chlorobenzyl \ aminomethylpyrrolidine The title compound was prepared using the procedure described in Example 63 using (R,S)-[l-(4-cyanopheneth-l-yl)-lH- imidazol-5-yl]acetic acid methyl ester in place of l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetic acid methyl ester. Anal, calc'd for C29H34N5O2CI 3.15 TFA, 0.65 H2O: C, 47.59; H, 4.35; N, 7.86. Found: C, 47.60; H, 4.35; N, 7.83. FAB HRMS exact mass calc'd for C29H35N5O2CI 520.247928(MH+), found 520.247518. EXAMPLE 66 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-benzyloxy-2(S)- f N'-acetyl-N'-3-chlorobenzyl 1 aminomethylpyrolidine The title compound was prepared as in Example 58 using benzyl bromide in place of methyl iodide. Anal. calc'd for C33H34N5O2CI 2.75 TFA, 0.95 H2O: C, 51.45; H, 4.33; N, 7.79. Found: C, 51.45; H, 4.37; N, 7.70. FAB HRMS exact mass calc'd for C33H35N5O2CI 568.247928(MH+), found 568.247609 EXAMPLE 67 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl 1 aminomethyl pyrrolidine The title compound was prepared as in Example 63 using 4(R)-benzyloxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl pyrrolidine Anal, calc'd for C34H36N5O2CI 3.00 TFA, 0.85 H2O: C, 51.14; H, 4.37, N, 7.45. Found: C, 51.15; H, 4.42; N, 6.86. FAB HRMS exact mass calc'd for C34H37N5O2CI 582.263579(MH+), found 582.263900. EXAMPLE 68 N-{ l-(4-Cyanobenzyl)-5-imidazolacetyl}-4(R)-benzyloxy-2(S)-{N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compound was prepared as in Example 60 using 4(R)-benzyloxy-2(S)-{ N'-acetyl-N'-3-chlorobenzyl-aminomethyl } pyrrolidine Anal, calc'd for C34H34N5O3CI 1.85 TFA, 0.60 H2O: C, 55.37; H, 4.57; N, 8.56. Found: C, 55.35; H, 4.53; N, 8.57. FAB HRMS exact mass calc'd for C34H35N5O3CI 596.242843(MH+), found 596.241293 EXAMPLE 69 N { 1 -(4-Cyanobenzyl)-5-imidazol-5-ylmethyl } -4(R)-(2-henylbenzyloxy)- 2(SV ( N'-acetyl-N'-3-chlorobenzyl \ aminomethylpyrrolidine The title compound was prepared as in Example 58 using 2- phenylbenzyl bromide in place of methyl iodide. Anal. calc'd for C39H38N5O2CI 2.50 TFA, 0.10 H2O: C, 56.76; H, 4.41; N, 7.52. Found: C, 56.78; H, 4.27; N, 7.16. FAB HRMS exact mass calc'd for C39H39N5O2CI 644.279229(MH+), found 644.279744 EXAMPLE 70 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(4- chlorobenzyloxy)-2(S)- { N'-acetyl-N'-3 - chlorobenzyl ) aminomethylpyrrolidine The title compound was prepared as in Example 58 using 4- chlorobenzyl bromide in place of methyl iodide. Anal, calc'd for C33H33N5O2CI2 3.15 TFA: C, 49.08; H, 3.79; N, 7.28. Found: C, 49.10; H, 3.67; N, 7.31. FAB HRMS exact mass calc'd for C33H34N5O2CI2 602.208956(MH+), found 602.208118 EXAMPLE 71 N { 1 -(4-Cy anobenzyl)-5-imidazolemethyl } -4(R)-(4-cyanobenzyloxy )- 2(S)-(N'-acetyl-N'-3-chlorobenzyl)aminomethylpyrrolidine The title compound was prepared as in Example 58 using 4- cyanobenzyl bromide in place of methyl iodide. Anal, calc'd for C34H33N6O2CI 2.85 TFA: C, 51.94; H, 3.94; N, 9.15. Found: C, 51.93; H, 3.83; N, 9.16. FAB HRMS exact mass calc'd for C34H34N6O2CI 593.243177 (MH+), found 593.243346 EXAMPLE 72 N{ 1 -(4-Cyanobenzyl)-5-imidazol-5-ylmethyl }-4(R)-(3-pyridylmethoxy)- 2(S)-{N'-acetyl-N'-3-chlorobenzyl}aminomethylpyrrolidine The title compound was prepared as in Example 58 using 3- picolyl chloride in place of methyl iodide. Anal. calc'd for C32H33N6O2CI 4.45 TFA: C, 45.22; H, 3.58; N, 7.74. Found: C, 45.20; H, 3.56; N, 7.86. FAB HRMS exact mass calc'd for C32H34N6O2CI 569.243177 (MH+), found 569.243177 EXAMPLE 73 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-£phenoxy)-2(S)- ( N'-acetyl-N'-3-chlorobenzyl I aminomethylpyrrolidine The title compound was prepared as in Example 58 using diphenyliodonium chloride in place of methyl iodide. Anal, calc'd for C32H32N5O2CI 2.75 TFA, 0.35 H2O: C, 51.54; H, 4.09; N, 8.01. Found: C, 51.55; H, 4.12; N, 7.75. FAB HRMS exact mass calc'd for C32H33N5O2CI 554.232278(MH+), found 554.232523. EXAMPLE 74 N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl } -4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N * -3- chlorobenzyl } aminomethylpyrrolidine The title compound was prepared as in Example 58 using 2- bromo methylacetate in place of methyl iodide. FAB HRMS exact mass calc'd for C29H33N5O4CI 550.222108MH+), found 550.221829. EXAMPLE 75 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(acetyloxy)-2(S)- ( N'-acetyl-N'-3-chlorobenzyl I aminomethylpyrrolidine To a solution of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- ylmethyl } -4(R)-(2-methylacetyloxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl- aminomethyl} pyrrolidine (43mg, 0.055mmol) in THF (0.5ml) was added lithium hydroxide (0.221ml, 0.221mmol) and the solution stirred at room temperatore for 16hrs. The reaction was quenched by the addition of trifluoroacetic acid (0.013ml) and the solvents evaporated in vacuo. The residue was purified by preparative HPLC (C-18, 95 to 5% water in acetonitrile containing 0.1% TFA, gradient elution), to afford the title compound. Anal, calc'd for C28-H30N5O4CI 2.95 TFA, 1.15 H2O: C, 45.59; H, 3.98; N, 7.84. Found: C, 45.59; H, 4.02; N, 7.83. EXAMPLE 76 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl ) aminomethylpyrrolidine The title compound was prepared as in Example 60 using 2- bromo methylacetate in place of methyl iodide. FAB HRMS exact mass calc'd for C30H33N5O5CI 578.217022(MH+), found 578.216687. EXAMPLE 77 N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl } -4(R)-£acetyloxy)-2(S)- { N'-3-chlorobenzyl-N'-acetyl I aminomethylpyrrolidine To a solution of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- ylacetyl}-4(R)-(2-methylacetyloxy)-2(S)-{N'-acetyl-N'-3-chlorobenzyl}- aminomethylpyrrolidine (38mg, 0.055mmol) in THF (0.5ml) was added lithium hydroxide (0.164ml, 0.164mmol) and the solution stirred at room temperature for 16 hrs. The reaction was quenched by the addition of trifluoroacetic acid (0.013ml) and the solvents evaporated in vacuo. The residue was purified by preparative HPLC (C-18, 95 to 5% water in acetonitrile containing 0.1% TFA, gradient elution) to afford the title compound. Anal, calc'd for C29H30N5O5CI 1.50 TFA, 1.15 H2O: C, 50.85; H, 4.51; N, 9.27. Found: C, 50.84; H, 4.54; N, 9.18. EXAMPLE 78 N{ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylmethyl }-4(S)-(phenoxy)-2(S)- ( N'-acetyl-N'-3-chlorobenzyl 1 aminomethylpyrrolidine Step A: Preparation of N-t-Butoxycarbonyl-4(S)-phenoxy-2(S)- { N'- acetyl-N' 3-chlorobenzyl } aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-4(S)-hydroxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine (200mg, 0.522mmol, prepared in step J Example 56), phenol (49. lmg, 0.522mmol) and triphenylphosphine (137.3mg, 0.524mmol), in THF (13.0ml), at room temperature was added diethylazodicarboxylate (0.083ml, O.53mmol) and the mixtored stirred for 16hrs. The solvent was evaporated in vacuo and the residue purified by chromatography (Siθ2, 50% EtOAc in hexanes) to afford the title compound as an oil. iH NMR CD3θD d 7.50-6.70 (9H, m), 5.10-5.00 (IH, m), 4.80- 4.20(3H, m), 4.00-3.20(4H, m), 2.40-2.00(5H, m) and 1.46(9H,s) ppm. Step B: 4(S)-Phenoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl }- aminomethylpyrrolidine The title compound was prepared by the procedure described in Example 1 step G using N-t-butoxycarbonyl-4(S)-phenoxy-2(S)-{N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine iH NMR(CD3θD, 400 MHz) δ 7.50-6.90 (9H, m), 5.18(1H, m), 4.70(2H, m), 4.10-4.00(1H, m), 3.94(1H, m), 3.63(1H, d, J=12.8Hz), 3.54(1H, dd, J=12.8 and 5.3Hz), 3.40(1H, dd, J=3.5 and 14.9Hz), 2.60(1H, m), 2.20(3H, s) and 2.00(1H, m) ppm. Step C: 1 -(4-Cyanobenzyl)-5-imidazolemethyl-4(R)-(ρhenoxy)-2(S)- {N'-3-chlorobenzyl-N'-acetyl} aminomethyl pyrrolidine The title compound was prepared as in Example 73 using 4(S)-(phenoxy)-2(S)- { N' acetyl-N'-3-chlorobenzyl } - aminomethylpyrrolidine Anal, calc'd for C32H32N5O2CI 2.70 TFA, 0.10 H2O: C, 52.01; H, 4.07; N, 8.11. Found: C, 52.03; H, 4.10; N, 7.96. FAB HRMS exact mass calc'd for C32H33N5O2CI 554.232278(MH+), found 554.231721. EXAMPLE 79 N{ l-(4-Cyanobenzyl)-5-imidazolethyl}-4(S)-(phenoxy)-2(S)-{N'-acetyl- N'-3-chlorobenzyl I aminomethylpyrrolidine The title compound was prepared as in Example 63 using 4(S)-(2-phenylbenzyloxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl }- aminomethylpyrrolidine Anal, calc'd for C33H34N5O2CI 2.00 HCl, 0.55 H2O: C, 60.89; H, 5.74; N, 10.76. Found: C, 60.90; H, 5.86; N, 11.06. FAB MS 567 (M+l). EXAMPLE 80 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl }-4(S)-fluoro-2(S)-{N'- acetyl-N'-3-chlorobenzyl ) aminomethylpyrrolidine Step A: N-t-Butoxycarbonyl-4(S)-fluoro -2(SMN'-acetyl-N * -3- chlorobenzyl \ aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-4(S)-hydroxy-2(S)- {N'-acetyl-N'-3-chlorobenzyl} aminomethylpyrrolidine (2.1 lg, 5.5 lmmol, prepared in step J Example 56, and diethylaminosulfur trifluoride (0.90ml, 6.8 lmmol), in CH2CI2 (120ml), at 0°C was stirred for lhr. Methanol (20ml) was added and after 30min the reaction was diluted with CH2CI2 and washed with saturated aqueous NaHC03 solution, dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue purified by chromatography (Siθ2, 1.5 to 2.5% MeOH in CH2CI2 gradient elution) to afford the title compound as an oil. Step B: Preparation of 4(S)-fluoro-2(S)- { N * -acetyl-N * -3- chlorobenzyl } aminomethylpyrrolidine The title compound was prepared by the procedure described in Example 1 step G using N-t-butoxycarbonyl-4(S)-fluoro-2(S)-{N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine Step C: N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl-4(S)-(fluoro)- 2(S)- ( N'-acetyl-N'-3-chlorobenzyl 1 aminomethyl pyrrolidine The title compound was prepared as in Example 63 using 4(S)-fluoro-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine. Anal, calc'd for C27H329N5OCIF 2.90 TFA: C, 47.77; H, 3.90;N, 8.49. Found: C, 47.80; H, 3.91; N, 8.46. FAB MS 494 (M+l) EXAMPLE 81 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl-4(R)-(2-phenylbenzyloxy)- 2(S)- ( N'-acetyl-N'-3-chlorobenzyl 1 aminomethylpyrrolidine The title compound was prepared as in Example 63 using 4(R)-(2-phenylbenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine Anal, calc'd for C40H40N5O2CI 3.15 TFA: C, 54.56; H, 4.29; N, 6.87. Found: C, 54.56; H, 4.03; N, 6.93. FAB HRMS exact mass calc'd for C40H41N5O2CI 658.294879(MH+), found 658.294834 EXAMPLE 82 N{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-(4-chlorobenzyloxy)- 7/S)- { N'-acety1-N'-3-chlorobenzyl ) aminomethylpyrrolidine The title compound was prepared as in Example 63 using 4(R)-(4-chlorobenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine Anal, calc'd for C34H35N5O2CI2 3.20 TFA, 0.15 H2O: C, 49.31; H, 3.94; N, 7.12. Found: C, 49.31; H, 3.72; N, 7.26. FAB HRMS exact mass calc'd for C34H36N5O2CI2 616.224606(MH+), found 616.223491 EXAMPLE 83 N{ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-4(R)-(4-cyanobenzyloxy 2(S)- { N'-acetyl-N'-3-chlorobenzyl \ aminomethylpyrrolidine The title compound was prepared as in Example 63 using 4(R)-(4-cyanobenzyloxy)-2(S)- { N'-acetyl-N"-3- chlorobenzyl } aminomethylpyrrolidine Anal, calc'd for C35H35N6O2CI 3.10 TFA, 0.10 H2O: C, 51.42; H, 4.01; N, 8.73. Found: C, 51.44; H, 3.90; N, 8.51. FAB HRMS exact mass calc'd for C35H36N6O2CI2 607.258827(MH+), found 607.259832. EXAMPLE 84 N{ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-4(R)-(3-pyridylmethoxy)- 2(S)- ( N'-acetyl-N'-3-chlorobenzyl 1 aminomethylpyrrolidine The title compound was prepared as in Example 63 using 4(R)-(3-pyridylmethoxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethyl-pyrrolidine. Anal, calc'd for C33H35N6O2CI 3.95 HCl , 1.10 EtOAc: C, 54.51; H, 5.84; N, 10.20. Found: C, 54.55; H, 6.07; N, 10.22. FAB HRMS exact mass calc'd for C33H36N6O2CI 583.258827(MH+), found 583.259083. EXAMPLE 85 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-2(S)-{N'-acetyl-N'-3- cy anobenzyl } aminomethylpyrrolidine Step A: Preparation of N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5- ylacetyl \ - 2(S)- ( N'-3-cvanobenzyl 1 aminomethylpyrrolidine To a slurry of 3-cyanobenzaldehyde (40.5mg, 0.309mmol), cmshed 3A molecular sieves (505mg), and N-{ l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl }-2(S)-aminomethyl} -pyrrolidine from Example 40 step E (100.9 mg, 0.312 mmol), and potassium acetate (51mg, o.54 mmol) in methanol (5 ml) was added sodium cyanoborohydride (0.31ml of a IM solution in THF, 0.31 mmol) at room temperatore. The reaction was stirred for 24 hrs, diluted with EtOAc and filtered. The filtrate was washed with saturated aqueous NaHCθ3, dried (Na2Sθ4) and evaporated in vacuo. The residue was purified by chromatography on a chromatatron (Siθ2, 5% NH4OH in acetonitrile) to provide the title compound as an oil. 1HNMR(CDC13, 400 MHz) d 7.80-6.80(10H, m), 5.45-5.30(2H, m), 4.25-3.80(3H, m), 3.60-3.30(4H, m), 2.95-2.50(2H, m) and 2.20-1.80(4H, m) ppm. Step B: N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-2(S)-{N'- acetyl-N'-3-cvanobenzyl 1 aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 40 step G using acetyl chloride instead of methane sulfonyl chloride. Anal, calc'd for C28-H28N602 0.25H2O, 1.50TFA; C, 56.75; H, 4.61; N, 12.81. Found: C, 56.74; H, 4.62; N, 12.72. FAB HRMS exact mass calc'd for C28H29N6O2481.235199(MH+), found 481.235799 EXAMPLE 86 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S)-{N'-acetyl-N'-3- methoxybenzyl } aminomethylpyrrolidine. The title compound was prepared using the protocol described in Example 85 using 3-methoxybenzaldehyde. Anal, calc'd for C28H31N5O3 0.35 H20, 1.50 TFA; C, 56.17; H, 5.05; N, 10.56. Found: C, 56.18; H, 5.06; N, 10.90. FAB HRMS exact mass calc'd for C28H32N5O3 486.250515(MH+), found 486.250698. EXAMPLE 87 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-3- trifluoromethylbenzyl } aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 3-trifluoromethylbenzaldehyde. Anal, calc'd for C28H28N5O2F3 0.45 H20, 2.20 TFA; C, 49.73; H, 4.01; N, 8.95. Found: C, 49.75; H, 3.99; N, 9.17. FAB HRMS exact mass calc'd for C28H29N5O2F3 524.227335(MH+), found 524.226844. EXAMPLE 88 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2- methoxybenzyl 1 aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 2-methoxybenzaldehyde. Anal, calc'd for C28-H31N5O3 0.50H2O, 2.15 TFA; C, 52.45; H, 4.65; N, 9.47. Found: C, 52.45; H, 4.67; N, 9.58. FAB HRMS exact mass calc'd for C28H32N5O3 486.250515 (MH+), found 486.249829. EXAMPLE 89 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2- trifluoromethylbenzyl I aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 2-trifluoromethylbenzaldehyde. Anal, calc'd for C28H28N5O2F3 0.40 H2O, 2.05 TFA; C, 50.43; H, 4.07; N, 9.16. Found: C, 50.43; H, 4.07; N, 9.24. FAB HRMS exact mass calc'd for C28H29N5O2F3 524.227335 (MH+), found 524.227352. EXAMPLE 90 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N * -acetyl-N'-(2 a 2z diphenylethyl) } aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using diphenylacetaldehyde. Anal, calc'd for C34H35N5O2 0.40 H2O, 1.60 TFA; C, 60.76; H, 5.13; N. 9.52. Found: C, 60.76; H, 5.11; N, 9.54. EXAMPLE 91 N- { l-(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl }-2(S)- { N'-acetyl-N'- diphenylmethyl ) aminomethylpyrrolidine Step A: N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S) diphenylmethyl I aminomethylpyrrolidine A solution of N-{ l-(4-Cyanobenzyl)-lH-imidazol-5- yl)acetyl}- 2(S)-aminomethyl-pyrrolidine (0.175mg, 0.544 mmol), triethylamine (0.055ml, 0.544mmol) and benzhydrylbromide (0.134mg, 0.544mmol) in DMF (2.0 ml) were stirred at room temperatore for 24hrs.. The reaction was quenched with saturated NaHCθ3 solution and extracted with EtOAc. The organic extracts were washed with brine, dried (MgS04), and evaporated in vacuo. The residue was purified by chromatography (Siθ2, 5% NH4OH in acetonitrile) to afford the title compound as an oil. Step B: N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'- acetyl-N'-diphenylmethyl 1 aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 41 using the material from step A. . Anal, calc'd for C33H33N5O2 1.00 H2O, 3.30 TFA; C, 51.37; H, 4.17; N, 7.56. Found: C, 51.36; H, 4.16; N, 7.85. FAB HRMS exact mass calc'd for C33H34N5O2 532.271251 (MH+), found 532.272495. EXAMPLE 92 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N , -2- chlorobenzyl 1 aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 2-chlorobenzaldehyde. Anal, calc'd for C27H28N5O2CI 1.00 H2O, 1.50 TFA; C, 53.06; H, 4.68; N, 10.31. Found: C, 53.04; H, 4.66; N, 10.32. EXAMPLE 93 AND 94 N-{2(R)-Methyl-2-(l-(4-Cyanobenzyl)-lH-imidazol-5-yl))acetyl}- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine and N- { 2(S)- Methyl-2-( 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl))acetyl } - 2(S)- { N'- acetyl-N'-3-chlorobenzyl ) aminomethylpyrrolidine Step A: 2(R,S)-Methyl-2-{ l-(Triphenylmethyl)-lH-imidazol-4-yl}- acetic acid methyl ester A solution of l-(triphenylmethyl)-lH-imidazol-4-ylacetic acid methyl ester (l.Olg, 2.63mmol) in THF (25 ml) was cooled to -78°C. Lithium hexamethyldisilazide (2.76ml of a IM solution in THF, 2.76 mmol) was added dropwise and the reaction stirred 30min at -78°C. Methyl iodide (0.164ml, 2.76mmol) was added and the reaction stirred a furthur 1 hr at -78°C and then at -20°C for 4 hrs. The reaction was quenched with water (10ml) and saturated NaHCθ3 solutoon (10ml) and extracted with EtOAc. The organic extracts were dried (MgSθ4) and the solvent evaporated in vacuo. Chromatography of the residue (Siθ2, 2 to 3% MeOH in CH2CI2, gradient elotion) afforded the product. 1H NMR CDC13, δ 7.40-7.00(16H, m), 6.71(lH, s), 3.77(lH, q, J=7.1Hz), 3.69(3H, s) and 1.47(3H, d, J=7.1Hz) ppm. Step B: 2(R,S)-Methyl-2-( 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)- acetic acid The title compound was prepared according to the procedure described in Example 1 steps C and D using the material from step A. IH NMR CDCI3, δ 8.15(lH, s), 7.75(2H, d, J=8.2Hz), 7.35(2H, d, J=8.2Hz), 7.15(1H, s), 5.44(2H, m), 3.50(1H, q, J=7.1Hz) and 1.45(3H, d, J=7.1Hz) ppm. Step C: N-{2(R)-Methyl-2-(l-(4-Cyanobenzyl)-lH-imidazol-5- yl))acetyl } - 2(S)- { N * -acetyl-N'-3-chlorobenzyl- aminomethyl} -pyrrolidine and N-{2(S)-Methyl-2-(l-(4- Cyanobenzyl)-lH-imidazol-5-yl))acetyl}- 2(S)-{N'-acetyl- N'-3-chlorobenzyl } aminomethylpyrrolidine The title compounds were prepared as an inseparable mixture using the protocol described in Example 85 using 2(R,S)-methyl- 2-(l-(4-cyanobenzyl)-lH-imidazol-5-yl)-acetic acid. Anal, calc'd for C28H30N5O2CI 0.55 H2O, 0.30 EtOAc, 1.55 HCl; C, 59.86; H, 5.98; N, 11.95. Found: C, 59.82; H, 5.99; N, 11.95. Anal, calc'd for C28H30N5O2CI 0.35 H2O, 0.25 EtOAc, 1.45 HCl; C, 59.52; H, 5.88; N, 11.97. Found: C, 59.52; H, 5.88; N, 11.90. EXAMPLE 95 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-3- chlorobenzyl \ aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 3-chlorobenzaldehyde. Anal, calc'd for C27H28N502C1 0.95 H2O, 1.50 TFA; C, 53.13; H, 4.67; N, 10.33. Found: C, 53.09; H, 4.65; N, 10.36. EXAMPLE 96 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N * -4- chlorobenzyl ) aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 4-chlorobenzaldehyde. Anal, calc'd for C27H28N502C1 1.05 H2O, 1.55 TFA; C, 52.73; H, 4.65; N, 10.47. Found: C, 52.71; H, 4.65; N, 10.47. EXAMPLE 97 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2,3- dichlorobenzyl I aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 85 using 2,3-dichlorobenzaldehyde. Anal, calc'd for C27H27N5O2CI2 0.20 H2O, 1.65 TFA; C, 50.82 H, 4.09; N, 9.78. Found: C, 50.82; H, 4.12; N, 9.80. EXAMPLE 98 N-[l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl-4(R)-benzyloxy-2(S)- ( N'-acetyl-N'-naphth- 1 - ylmethyl ) aminomethylpyrrolidine Step A: N-t-Butoxycarbonyl-4(R)-benzyloxyproline naphth-1- ylmethylamide The title compound was prepared using the procedure in Example 1 step H using N-t-butoxycarbonyl-4(R)- benzyloxyproline and naphth- 1 -ylmethylamine. StepB: N-t-Butoxycarbonyl-4(R)-benzyloxy-2(S)-{N'-naphth-l- ylmethyl) aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-4(R)-benzyloxy proline naphth- 1-ylmethylamide (1.20g, 2.606 mmol), in THF (34ml) at -35°C was added borane (5.20ml of a IM solution in THF, 5.2mmol). The reaction was allowed to warm to room temperatore and stirred for 16 hrs. The reaction was quenched with methanol (30ml) and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 50% EtOAc in hexanes), to afford the title compound as an oil. FAB MS 446 (M+l). Step C: N-t-Butoxycarbonyl-4(R-benzyloxy-2(S)- { N'-acetyl-N'- naphth- 1 - ylmethyl ) aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 40 step G using acetyl chloride. IHNMR (CDC13, 400 MHz) d 8.10-7.00Q2H, m), 5.70-2.90(13H, m), 2.40-2.00(2H, m) and 1.45(9H, s)ppm. FAB MS 489(M+1). Step D: 4(R)-Benzyloxy-2(S)- { N'-acetyl-N'-naphth- 1 -ylmethyl } - aminomethylpyrrolidine hydrochloride The title compound was prepared using the protocol described in Example 1 step G and the compound prepared in step C. lHNMR(CD30D, 400 MHz) δ 8.00(1H, d, J=8.6Hz), 7.94(1H, d, J=7.1Hz), 7.87(1H, d, J=8.2Hz), 7.70--7.40(3H, m), 7.40-7.20(6H, m), 5.24(1H, d, J=17.6Hz), 5.16(1H, d, J=17.6Hz), 4.50(1H, d, J=11.7Hz), 4.47QH, d, J=11.7Hz), 4.31(1H, t, J=4.5Hz), 4.05(1H, m), 3.90(1H, m), 3.60-3.30(3H, m), 2.12(1H, m), 2.20(3H, s) andl.89(lH, m) ppm. FAB MS 389 (M+l). Step E: Preparation of N-[l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetyl-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-naphth- 1 - ylmethyl } aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 1 step H and the compound prepared in step D. Anal, calc'd for C38H37N5O3 0.15H2O, 1.95 TFA; C, 60.14; H, 4.73; N, 8.37. Found: C, 60.16; H, 4.76; N, 8.31. FAB HRMS exact mass calc'd for C38H38N5O3 612.297465 (MH+), found 612.298079. EXAMPLE 99 N-[l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl-4(R)-benzyloxy-proline naphth- 1 -ylmethylamide The title compound was prepared using the protocol described in Example 1 step H and 4(R)-benzyloxy proline naphth- 1- ylmethylamide. Anal, calc'd for C36-H33N5O3 0.60 H2θ, 1.50T FA; C, 61.19; H, 4.70; N, 9.15. Found: C, 61.21; H, 4.67; N, 9.21. FAB HRMS exact mass calc'd for C36H34N5O3 584.266165 (MH+), found 584.267734. EXAMPLE 100 N- [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetylproline naphth- 1 - ylmethylamide The title compound was prepared using the protocol described in Example 99 and proline naphth- 1 -ylmethylamide Anal, calc'd for C29H27N5O2 0.65 H2O, 1.00 TFA; C, 61.72; H, 4.90; N, 11.61. Found: C, 61.70; H, 5.05; N, 11.58. FAB HRMS exact mass calc'd for C29H28N5O2 478.224300 (MH+), found 478.224053. EXAMPLE 101 N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)-methoxy-2(S)-{N'- acetyl-N'-5.6.7.8-tetrahvdronaphth-l-ylmethyllaminomethylpyrrolidine Step A: N-t-Butoxycarbonyl-4(R)-hydroxy-2(S)- { N'-acetyl-N'- 5,6,7,8-tetrahydronaphth-l-ylmethyl}aminomethyl- pyrrolidine The title compound was prepared using the protocol described in Example 56 step G and N-t-butoxycarbonyl-4(R)-benzyloxy- 2(S)- { N'-acetyl-N'-naphth- 1 -ylmethyl } aminomethylpyrrolidinefrom Example 98, Step C. FAB MS 403 (M+l). Step B: N-t-Butoxycarbonyl-4(R)-methoxy-2(S)-{N'-acetyl-N'- 5,6,7,8-tetrahydronaphth- 1- ylmethyl ) aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 58 step A using N-t-butoxycarbonyl-4(S)-hydroxy- 2(S)-{N'-acetyl-N'-5,6,7,8-tetrahydronaphthylmethyl}- aminomethylpyrrolidine from Step A. Step C: 4(S)-Methoxy-2(S)- { N'-acetyl-N'-tetrahydronaphth- 1 - ylmethyl I aminomethylpyrrolidine hydrochloride The title compound was prepared using the protocol described in Example 1 step G. Step D: N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)- methoxy-2(S)- { N'-acetyl-N'-5,6,7,8-tetrahydronaphth- 1 - ylmethyl I aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 1 step H. Anal, calc'd for C32H37N5O3 0.40 H2O, 2.25 TFA; C, 54.57; H, 5.02; N, 8.72. Found: C, 54.57; H, 5.02; N, 8.82. FAB HRMS exact mass calc'd for C32H38N5O3 540.297465(MH+), found 540.296505. EXAMPLE 102 N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-5,56,7,8-tetrahydronaphth- 1 -ylmethyl } aminomethyl- pyrrolidine The title compound was prepared using the protocol described in Example 101 using benzyl bromide in place of methyl iodide. Anal, calc'd for C38H41N5O3 0.40H2O, 2.05 TFA; C, 59.02; H, 5.16; N, 8.17. Found: C, 59.01; H, 5.15; N, 8.22. FAB HRMS exact mass calc'd for C38H42N5O3 616.328766 (MH+), found 616.327514. EXAMPLE 103 l-(4-Cyanobenzyl)- lH-imidazol-5-ylmethyl-2(S)- { N'-acetyl-N'-3- chlorobenzyl ) aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 56 step M and 2(S)-{N'-acetyl-N'-3 chlorobenzyl } amino-methylpyrrolidine. Anal, calc'd for C26H28N5OCI 0.50 H2O, 2.65 TFA; C, 48.96; H, 4.22; N, 8.98. Found: C, 48.96; H, 4.20; N, 8.81. FAB HRMS exact mass calc'd for C26H29N5OCI 462.206064 (MH+), found 462.206270. EXAMPLE 104 N-Allyloxycarbonyl-2(S)- { ( 1 -(4-Cyanobenzyl)- 1 H-imidazol-5- vPacetyl 1 amino-3 (S )-methyl-pentanamine Step A: 2(S)-N-t-Butoxycarbonylamino-3(S)-methyl-pentanamine The title compound was prepared using the procedure described in Example 40 steps B, C and E using 2(S)-N-t- butoxycarbonylamino-3(S)-methyl-pentanol in place of 2(S)-N-t- butoxycarbonylhydroxymethyl pyrrolidine. iH NMR(CDCl3, 400 MHz) δ 4.55(1H, s), 3.60-3.40(3H, m), 2.83(1H, m), 2.62(1H, m), 1.60(1H, m), 1.45(9H, s) and 1.30-0.80(8H, m)ppm. Step B: N-Allyloxycarbonyl-2(S)-N-t-butoxycarbonylamino-3(S)- methyl-pentanamine A solution of 2(S)-N-t-butoxycarbonylamino-3(S)-methyl- pentanamine (1.921g, 8.88mmol), triethylamine (2.50ml, 18.0 mmol) in CH2CI2 (90ml) was treated with allylchloroformate (1.45 ml, 8.88 mmol) at 0°C and the reaction allowed to warm to room temperatore and stirred for 16 hrs. The solvent was evaporated in vacuo and the residue chromatographed (Siθ2, 15-20% EtOAc in hexanes to afford the title compound as an oil. lHNMR(CDCl3, 400 MHz) δ 5.92(1H, m), 5.30(1H, d, J=17.5Hz), 5.22(1H, d, J=10.0Hz), 5.10(1H, s), 4.60-4.50(3H, m), 3.58(1H, s), 3.40- 3.20(2H, m), 1.60(1H, m), 1.45(9H, s) and 1.25-0.90(8H, m)ppm. Step C: N-jAllyloxycarbonyl-2(S)-amino-3(S)-methyl-pentanamine hydrochloride The title compound was prepared by the procedure described in Example 1 step G. lHNMR(CD30D, 400 MHz) δ 5.95(lH,m), 5.35(1H, d, J=17.5Hz), 5.22(1H, d, J=10.0Hz), 4.60(2H, s), 3.60-3.10(3H, m), 1.78(1H, m), 1.60(1H, m) and 1.25(lH,m) andl.lO-0.90(6H, m) ppm. Step D: N-Allyloxycarbonyl-2(S)-{ (l-(4-Cyanobenzyl)-lH- imidazol-5-yl)acetyl I amino-3(S)-methyl-pentanamine The title compound was prepared by the procedure described in Example 1 step G using N-Allyloxycarbonyl-2(S)-amino- 3(S)-methyl-pentanamine hydrochloride. Anal, calc'd for C23H29N5O 0.25 H2O; C, 64.54; H, 6.95; N, 16.36. Found: C, 64.56; H, 6.86; N, 16.04. FAB HRMS exact mass calc'd for C23H30N5O 424.234865 (MH+), found 424234627. EXAMPLE 105 2(S)-{(l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}amino-3(S)-methyl- N-(naphth-2-ylsulfonyl)-pentanamine Step A: 2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)acetyl } amino- 3(S)-methyl-pentanamine To a solution of N-allyloxycarbonyl-2(S)-{(l-(4- cyanobenzyl)-lH-imidazol-5-yl)acetyl}amino-3(S)-methyl-pentanamine (2.372g, 5.60mmol) and 5,5- dimethyl- 1,3-cyclohexanedione (6.21g, 44.3mmol) in THF (70ml) was added (tetrakistriphenylphosphine) palladium (0) (1.12g, 0.969mmol) and the reaction was stirred in the dark for 2 hrs. The solvent was evaporated in vacuo and the residue partitioned between Et2θ and IM aqueous HCl. The aqueous layer was treated with Na2C03 solution until pH 10 and extracted with EtOAc. The organic extracts were washed with brine, dried (Na2Sθ4), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 3% NH4OH in acetonitrile) to afford an enamine. The title compound was obtained by treating the enamine with bromine water following the procedure of Halpem Aust. J. Chem .17 1964, 1282. FAB HRMS exact mass calc'd for C19H26N5O 340.213736 (MH+), found 340.213895. Step B: 2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl)acetylamino } - 3 ( S ) -methyl-N- ( naphth-2-ylsulfonyl)-ρentanamine The title compound was prepared using the protocol described in Example 40 step G using naphth-2-ylsulfonyl chloride instead of methane sulfonyl chloride. Anal, calc'd for C29H31N5O3S 0.30 H2O, 1.65 TFA; C, 53.64; H, 4.63; N, 9.68. Found: C, 53.62; H, 4.67; N, 9.69. FAB HRMS exact mass calc'd for C29H32N5O3S 530.222587 (MH+), found 530.224351. EXAMPLE 106 2(S)-[l-(4-Cyanobenzyl)-lH-imidazol-5-yl}acetyl}amino-3(S)-methyl-N- (naphth- 1 -ylsulf onyP-pentanamine The title compound was prepared using the protocol described in Example Example 105 using naphth- 1 -ylsulf onyl chloride. Anal, calc'd for C29H31N5O3S 0.40 H2O, 1.40 TFA; C, 54.84; H, 4.80; N, 10.06. Found: C, 54.87; H, 4.81; N, 10.08. FAB HRMS exact mass calc'd for C29H32N5O3S 530.222587 (MH+), found 530.221441. EXAMPLE 107 N-Acetyl-N-2-chlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yPacetyl ) amino-3(S)-methyl-pentanamine Step A: N-2-chlorobenzyl-2(S)- { l-(4-Cyanobenzyl)- lH-imidazol-5- yPacetyl)amino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 10 step G using 2-chlorobenzaldehyde and the amine from Example 105 step A. FAB MS 464 (M+l). Step B: N-Acetyl-N-2-chlorobenzyl-2(S)-{ (l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl)amino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 41 using the amine from step A. FAB HRMS exact mass calc'd for C28H33N5O2CI 506.232278 (MH+), found 506.233741. EXAMPLE 108 N-Acetyl-N-3-chlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yPacetyl 1 amino-3(S)-methyl-pentanamine Step A: N-3-Chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5*: yl)acetyllamino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 10 step G using 3-chlorobenzaldehyde and the amine from Example 105 step A. FAB MS 464 (M+l) Step B: N- Acetyl-N-3-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl } amino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 41 using the amine from step A. FAB HRMS exact mass calc'd for C28H33N5O2CI 506.232278 (MH+), found 506.231892. EXAMPLE 109 N- Acetyl-N-4-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl)acetyllamino-3(S)-methyl-pentanamine Step A: N-4-Chlorobenzyl-2(S)-{(l-(4-Cyanobenzyl)-lH-imidazol- 5-yl)acetyl)amino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 10 step G using 4-chlorobenzaldehyde and the amine from Example 105 step A. FAB MS 464 (M+l) Step B: N-Acetyl-N-4-chlorobenzyl-2(S)-{ (l-(4-Cyanobenzyl)-lH- imidazol-5-yl)acetyllamino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 41 using the amine from step A. Anal, calc'd for C28-H32N5O2CI 1.00 H2θ, 1.95 TFA; C, 51.33; H, 4.85; N. 9.38. Found: C, 51.34; H, 4.84; N, 9.28. FAB HRMS exact mass calc'd for C28H33N5O2CI 506.232278 (MH+), found 506.232238. EXAMPLE 110 N-Acetyl-N-2,3-dichlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-iιm^azol- 5-yl)acetyl}amino-3(S)-methyl-pentanamine Step A: N-2,3-Dichlorobenzyl-2(S)-{ (l-(4-Cyanobenzyl)-lH- imidazol-5-yl)acetyl \ amino-3 (S Vmethyl-pentanamine The title compound was prepared using the protocol described in Example 10 step G using 2,3-dichlorobenzaldehyde and the amine from Example 105 step A. FAB MS 498 (M+l). Step B: N-Acetyl-N-3-chlorobenzyl-2(S)-{ (l-(4-Cyanobenzyl)-lH- imidazol-5-yl)acetyl}amino-3(S)-methyl-pentanamine The title compound was prepared using the protocol described in Example 41 using the amine from step A. Anal, calc'd for C28H31N5O2CI2 0.30 H2O, 1.85 TFA; C, 50.31; H, 4.45; N, 9.25. Found: C, 50.32; H, 4.47; N, 9.43. FAB HRMS exact mass calc'd for C28H32N5O2CI2 540.193327 (MH+), found 540.193425. EX AMPLE 111 N- Allyloxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { 2(R,S)-methyl-2-( 1 -(4- cyanobenzyP-lH-imidazol-5-yl)acetyπamino-3(S)-methyl-pentanamine The title compound was prepared according to the procedures described in Example 1 using 2(R,S)-methyl-2-{(l-(4- cyanobenzyl)-lH-imidazol-5-yl } acetic acid. Anal, calc'd for C35H39N5O3 0.05 H20, 1.45 TFA; C, 61.19; H, 5.49; N, 9.41. Found: C, 61.15; H, 5.50; N, 9.58. EXAMPLE 112 N-t-Butoxycarbonylaminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4- cyanobenzyP-lH-imidazol-5-ylacetyl}amino-3(S)-methylpentanamine The title compound was prepared using the protocol described in Example 1 step H using N-t-butoxycarbonyl glycine and N- naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5- ylacetyl}amino-3(S)-methyl pentanamine from Example 2. FAB HRMS exact mass calc'd for C37H45N6O4 630.350229(MH+), found 637.350834. EXAMPLE 113 N- Aminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H- imidazol-5-ylacetyl \ amino-3 (S)-methylρentanamine The title compound was prepared using the protocol described in Example 1 step G using N-t-butoxycarbonylaminoacetyl-N- naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- lH-imidazol-5- ylacetyl}amino-3(S)-methylpentanamine. Anal, calc'd for C32H36N6O2 3.10 HCl; C, 59.16; H, 6.07; N, 12.94. Found: C, 59.09; H, 6.27; N, 12.85. FAB HRMS exact mass calc'd for C32H37N6O2 537.297800(MH+), found 537.297766. EXAMPLE 114 N- { 5-(4-Cyanobenzyl)- 1 H-imidazol- 1 -yl)ethyl } -2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 44 using 2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethyl-pyrrolidine. Anal, calc'd for C27H30N5OCI 2.00 HCl, 0.70 H2O; C, 57.75; H, 6.00; N, 12.47. Found: C, 57.75; H, 6.04; N, 12.20. EXAMPLE 115 N- { 5-(4-Cyanobenzyl)- 1 H-imidazol- 1 -yl)ethoxycarbonyl } -2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine The title compound was prepared using the protocol described in Example 44 using 2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethyl-pyrrolidine Anal, calc'd for C28H30N5O3CI 2.10 HCl, 0.60 EtOAc; C, 56.22; H, 5.73; N, 10.78. Found: C, 56.20; H, 5.48; N, 10.75. EXAMPLE 116 N-{5-(4-Cyanobenzyl)-lH-imidazol-l-ylacetyl}-2(S)-{N'-acetyl-N * -3- chlorobenzyl } aminomethylpyrrolidine The title compound was prepared using the procedure described in Example 42 using 2(S)-{N'-acetyl-N'-3-chlorobenzyl} amino¬ methylpyrrolidine Anal, calc'd for C27H28N5O2CI 1,00 HCl, 1.50 H2O, 0.16 EtOAc; C, 60.22; H, 6.06; N, 12.77. Found: C, 60.21; H, 5.82; N, 12.48. EXAMPLE 117 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)ethyl}-2(S)-{N'-acetyl-N * -3- chlorophenyl I aminomethylpyrrolidine Step A: N-t-Butoxycarbonyl-2(S)- { N'-acetylaminomethyl }- pyrrolidine The title compound was prepared using the procedure described in Example 41 using N-t-butoxycarbonyl-2(S)-aminomethyl- pyrrolidine. Step B: N-t-Butoxycarbonyl-2(S)- { N'-acetyl-N'-3-chlorophenyl } - aminomethylpyrrolidine To a solution of N-t-butoxycarbonyl-2(S)-{N'- acetyl } aminomethylpyrrolidine ( 1.55g, 6.40 mmol) and triethylamine (1.34ml, 9.60 mmol) in CH2CI2 (50 ml) was added tri-(3- chlorophenyl)bismuth (6.86g, 12.62 mmol) and copper II acetate (1.74g, 9.60 mmol). The reaction was stirred at room temperatore for 16hrs, silica gel (75g) was added and the mixture filtered. The solid was washed with 5% MeOH in CH2CI2. The filtrate was evaporated in vacuo and the residue purified by chromatography (Siθ2, 10-100% EtOAc in hexanes, gradient elution) to afford the title compound as an oil. iH NMR (CDCI3, 400 MHz) δ 7.60-7.20(4H, m), 4.25(1H, m), 3.90(1H, m), 3.80(1H, m), 3.50-3.20(2H, m), 2.20-1.80(7H, m) and 1.50-1.10(9H, m)ppm. Step C: 2(S)- { N'-Acetyl-N'-3-chlorophenyl } aminomethyl- pyrrolidine hydrochloride The title compound was prepared using the procedure described in Example 1 step G and the material prepared in step B. iH NMR (CDC13, 400 MHz) δ 7.54-7.46(3H, m), 7.35-7.30(lH, m), 4.30(1H, m), 3.75-3.65(2H,m), 3.48-3.38(2H, m), 2.20-2.02(3H,m), 1.92(3H, s), 1.78-1.66(1H, m) ppm. Step D: N-{ l-(4-Cyanobenzyl)-lH-inιidazol-5-yl)ethyl}-2(S)-{N'- acetyl-N'-3-chlorophenyl } aminomethylpyrrolidine The title compound was prepared using the procedure described in Example 63 using 2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine. FAB HRMS exact mass calc'd for C26H29N5OCI 462.206064(MH+), found 462.207329. EXAMPLE 118 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-{N * -acetyl-N'-3 chlorophenyl 1 aminomethylpyrrolidine hydrochloride The title compound was prepared using the procedure described in Example 56 using 2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethyl-pyrrolidine. Anal, calc'd for C25H26N5OCI 2.40HC1, 1.40H2O; C, 53.56; H, 5.61; N, 12.49. Found: C, 53.60; H, 5.60; N, 12.36. EXAMPLE 119 N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine The title compound was prepared using the procedure described in Example 1 step H using 2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine. Anal, calc'd for C26H26N5OCI 1.30 HCl, 0.50 H2O; C, 58.66; H, 5.36; N, 13.15. Found: C, 58.66; H, 5.37; N, 13.06. EXAMPLE 120 N-[l-(3-[lH-Imidazol-4-yl]ρropionyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)glvcine N'-(3-chlorophenyl)amide Step A: 2-Methylbenzylglycine methyl ester hydrochloride To a solution of 2-methylbenzyl alcohol (100 g, 0.82 mol) and diisopropylethylamine (171 mL, 0.98 mol) in CH2CI2 (400 mL) at -5°C was added dropwise methanesulfonyl chloride (74 mL, 0.95 mmol) with stirring under argon. After 1 hr at -5° and 3 hr at 20°C, this solution was added dropwise simultaneously with diisopropylethylamine (428 mL, 2.46 mol) to a slurry of glycine methyl ester hydrochloride (308.8 g, 2.45 mol) in DMF (400 mL) at 0°C. The reaction mixture was allowed to warm to ambient temperatore for overnight, then treated slowly with satd NaHC03 solution (1 L) and EtOAc (1 L). The layers were separated, the aqueous washed with EtOAc, and the organics combined, washed with satd NaHC03 solution, brine, and dried (MgS04). This solution was filtered, cooled to 0°C, and HCl was bubbled into the solution to precipitate the title compound. iH NMR (CDCI3) δ 7.61 (d, IH, J = 7 Hz), 7.7 -7.8 (m, 3H), 4.31 (s, 2H), 3.77 (s, 3H), 3.65 (s, 2H), 2.46 (s, 3H). Step B: N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyP-glycine methyl ester 2-Methylbenzylglycine methyl ester hydrochloride(36.7 g, 0.16 mol) and N-[(teττ-Butyloxy)carbonyl-prolinal (Pettit et al., J. Org. Chem. (1994) 59, [21] 6287-95) (31.6 g, 0.159 mol) were dissolved in CH2CI2 (500 mL), treated with 3A molecular sieves (2 Og) and stirred for 18 hrs at room temperatore under argon. The reaction mixture was filtered, quenched with aq satd NaHC03 (5 mL) and concentrated and the residue was extracted with EtOAc 3 x 200 mL). The extracts were combined, washed with aq satd NaHCθ3 solution, brine, and dried (MgSθ4). Filtration and concentration the title compound as a yellow oil which was used without further purification. Step C: N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzvP-glvcine N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)-glycine methyl ester (41.85 g, 0.111 mol) was dissolved in CH3OH (300 mL) at 0°C. and treated with 2 N NaOH solution (111 mL, 0.222 mol) and allowed to stir at ambient temperatore for 3 hr. 1 N HCl (235 mL, 0.235 mol) was added, the CH3OH was removed on a rotary evaporator, and the residue was extracted with EtOAc (2 x 1.5 L), washed with brine, and dried (MgSθ4). Filtration and concentration to dryness gave the title compound as a white solid. A H NMR (CD3OD) δ 7.56 (d, IH, J = 7.5 Hz), 7.15 -7.36 (m, 3H), 4.70 (d, IH, J = 13 Hz), 4.27 (d, IH, J = 13 Hz), 4.1 - 4.2 (m, IH), 3.73 (d, IH, J = 16 Hz), 3.59 (d, IH, J = 16 Hz), 3.15 - 3.5 (m, 4H), 2.49 (s, 3H), 2.1 - 2.2 (m, IH), 1.7 - 1.9 (m, 2H), 1.6 - 1.7 (m, IH), 1.46 (s, 9h). Step D: N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzvP- glvcine N'-3-chlorophenyl)amide N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)-glycine (5.4 g, 0.115 mol), 3-chloroaniline (2.4 mL, 0.227 mol), HOOBT ( 3.65 g, 0.224 mol), and EDC (4.28 g, 0.223 mol) were dissolved in DMF (20 mL) at ambient temperatore and the pH was adjusted with Et3N (3.10 mL, 0.222 mol). After stirring overnight, the mixture was concentrated to remove the DMF, and the residue partitioned between EtOAc and H2θ. The aqueous layer was extracted with EtOAc, the organics combined, washed with H2O, brine, and dried (MgSθ4), then filtered and concentrated to give the title compound as a yellow oil. Step E: Pyrrolidin-2(S)-ylmethyl-(N-2-methylbenzyl)- glycine N'- chlorophenyl) amide hydrochloride N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)- glycine N'-(3-chlorophenyl) amide (2.56 g, 5.42 mmol) was dissolved in EtOAc (125 mL), cooled to 0°C, and HCl gas was bubbled into the solution for 10 min followed by stirring under argon for 3 hr. Argon was bubbled into the solution and the solvent was removed in vacuo to give the title compound as a white amorphous solid. Step F: N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)- ylmethyl]-(N-2-methylbenzyl)glycine N'-(3-chlorophenyl) amide hydrochloride Pyrrolidin-2(S)-ylmethyl]-(N-2-methylbenzyl)- glycine N'- (3-chlorophenyl) amide hydrochloride (0.26 g, 0.58 mmol), lH-imidazol- 4-yl]propionic acid hydrochloride (0.26 g, 1.5 mmol), EDC (0.22 g, 1.1 mmol), HOOBT (0.19 g, 1.2 mmol) were dissolved in DMF (19 mL) at 25°C, the pH of the mixture adjusted to 8 with Et3N (0.485 mL, 3.48 mmol). After stirring for 18 h, the reaction mixture was partitioned between EtOAc and satd NaHC03 solution, the organic layer separated, washed with brine, dried (MgSθ4), filtered, and concentrated to dryness to give the title compound after preparative RP HPLC (Vydac column, 0.1% TFA/CH3CN: 0.1% TFA/H20, 95:5 to 5:95 gradient), lyophilization, and conversion to its HCl salt. Anal, calcd for C27H32N5O2CI • 2 HCl • 1.6 H2O: C, 54.43; H, 6.29; N, 11.76; found: C, 54.44; H, 6.48; N, 11.56. FAB MS 494 (M+l). EXAMPLE 121 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl] pyrrolidin-2(S)- ylmethyl]-(N-2-methylbenzyl)-glycine N'-(3-chlorophenylmethyl) amide hydrochloride l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid (0.14g, 0.494 mmol), pyrrolidin-2(S)-ylmethyl]-(N-2-methylbenzyl)-glycine N'- (3-chlorophenyl) amide hydrochloride (Example 120, Step E) (0.109 g, 0.245 mmol), EDC (0.09 g, 0.469 mmol), HOOBT (0.08 g, 0.49 mmol) were dissolved in DMF (5 mL) at 25 °C, the pH of the mixture adjusted to 8 with Et3N (0.205 mL, 1.47 mmol). After stirring for 18 h, the reaction mixture was partitioned between EtOAc and satd NaHC03 solution, the organic layer separated, washed with brine, dried (MgSθ4), filtered, and concentrated to dryness to give the title compound after preparative RP HPLC (Vydac column, 0.1% TFA/CH3CN: 0.1% TFA H2O, 95:5 to 5:95 gradient), lyophilization, and conversion to its HCl salt. Anal, calcd for C34H35N6O2CI • 2.1 HCl • 0.95 H2O: C, 59.30; H, 5.71; N, 12.20; Found: C, 59.34; H, 5.71; N, 11.85. FAB MS 595 (M+l). EXAMPLE 122 N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzvP- lvcine N'-methyl-N'-(3-chlorophenyl) amide Step A: N-[(t-Butyloxycarbonyl)-pyιτolidin-2(S)-ylmethyl]-(N-2- methylbenzvP-glvcine N'-methyl-N'-3-chlorophenyl) amide N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-(N-2- methylbenzyl)- glycine-N-3-chlorophenyl) amide (Example 120, Step D) (3.97 g, 8.41 mmol) was dissolved in dry THF (40 mL) with stirring at 0°C under Ar, treated with NaH (60% dispersion in mineral oil, 0.68 g, 17 mmol), and after 15 min treated with iodomethane (2.10 mL, 33.7 mmol). The reaction mixture was stirred at 25 °C. for 4 h, then evaporated to dryness and partitioned between EtOAc and aq satd NaHCθ3 solution. The organic layer was separated, washed with brine, dried (MgS04), filtered, and concentrated to dryness to give the title compound as a white solid. FAB MS 486 (M+l). Step B: Pyrrolidin-2(S)-ylmethyl]-(N-2-methylbenzyl)-glycine N'- methyl-N'-(3-chlorophenyl) amide hydrochloride N- [(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]- (N-2- methylbenzyl)- glycine N'-methyl-N'-(3-chlorophenyl) amide (3.75 g, 7.17 mmol) was dissolved in EtOAc (125 mL), cooled to 0°C, and HCl gas was bubbled into the solution for 10 min followed by stirring under argon for 3 hr. Argon was bubbled into the solution and the solvent was removed in vacuo to give the title compound as a white amorphous solid which was used without further purification. Step C: N-[ 1 -(3- [ 1 H-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)-y lmemyl]-(N-2-metoylbenzyl)glycine N'-methyl-N'-(3- chlorophenyl) amide hydrochloride Pyrrolidin-2(S)-ylmethyl]-(N-2-methylbenzyl)- glycine-N- methyl-N-(3-chlorophenyl) amide hydrochloride (0.43 g, 0.94 mmol), lH-imidazol-4-yl]propionic acid hydrochloride (0.33 g, 1.9 mmol), EDC (0.36 g, 1.9 mmol), HOOBT (0.31 g, 1.9 mmol) were dissolved in DMF (20 mL) at 25°C, the pH of the mixture adjusted to 8 with Et3N (0.917mL, 6.58 mmol). After stirring for 72 h, the reaction mixture was partitioned between EtOAc and satd NaHCθ3 solution, the organic layer separated, washed with brine, dried (MgSθ4), filtered, and concentrated to dryness to give the title compound after preparative RP HPLC (Vydac column, 0.1% TFA/CH3CN: 0.1% TFA/H2O, 95:5 to 5:95 gradient), lyophilization, and conversion to its HCl salt. Anal, calcd for C28H34N5O2CI • 2 HCl • 0.5 H2O: C, 57.00; H, 6.32; N, 11.87; Found: C, 56.98; H, 6.57; N, 11.51. FAB MS 508 (M+l). EXAMPLE 123 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl] pyrrolidin-2(S)- ylmethyl]-(N-2-methylbenzyl)-glycine N'-methyl-N'-(3- chlorophenylmethyl) amide hydrochloride l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid (0.14 g, 0.494 mmol), pyrrolidin-2(S)-ylmethyl]-(N-2-methylbenzyl)- glycine N'- methyl-N'-3-chlorophenyl) amide hydrochloride (Example 122, Step B) (0.107 g, 0.232 mmol), EDC (0.09 g, 0.469 mmol), HOOBT (0.08 g, 0.49 mmol) were dissolved in DMF (5 mL) at 25°C, the pH of the mixture adjusted to 8 with Et3N (0.194 mL, 1.39mmol). After stirring for 18 h, the reaction mixture was partitioned between EtOAc and satd NaHC03 solution, the organic layer separated, washed with brine, dried (MgS04), filtered, and concentrated to dryness to give the title compound after preparative RP HPLC (Vydac column, 0.1% TFA/CH3CN: 0.1% TF.A/H20, 95:5 to 5:95 gradient), lyophilization, and conversion to its HCl salt. Anal, calcd for C35H37N6O2CI • 2.15 HCl • 1.25 H2O: C, 59.22; H, 5.91; N, 11.84; Found: C, 59.22; H, 5.92; N, 11.67. FAB MS 609 (M+l). EXAMPLE 124 (S)-2-[(l-(4-cyanobenzyl)-5-inύdazolylmethyl)amm dimethylphenyPacetamidolhexane hydrochloride Step A: l-Triphenylmethyl-4-(hydroxymethyPimidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35 g) in 250 mL of dry DMF at room temperatore was added triethylamine (90.6 mL). A white solid precipitated from the solution. Chlorotriphenylmethane (76.1 g) in 500 mL of DMF was added dropwise. The reaction mixtore was stirred for 20 hours, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid which was sufficiently pure for use in the next step. Step B: l-Triphenylmethyl-4-(acetoxymethyPimidazole Alcohol from Step A was suspended in 500 mL of pyridine. Acetic anhydride (74 mL) was added dropwise, and the reaction was stirred for 48 hours during which it became homogeneous. The solution was poured into 2 L of EtOAc, washed with water (3 x 1 L), 5% aq. HCl soln. (2 x 1 L), sat. aq. NaHCθ3, and brine, then dried (Na2S04), filtered, and concentrated in vacuo to provide the cmde product. The acetate was isolated as a white powder which was sufficiently pure for use in the next step. Step C: l-(4-Cyanobenzyl)-5-(acetoxymethyl)imidazole hydrobromide A solution of the product from Step B and oc-bromo-/?- tolunitrile (50.1 g) in 500 mL of EtOAc was stirred at 60 °C for 20 hours, during which a pale yellow precipitate formed. The reaction was cooled to room temperatore and filtered to provide the solid imidazolium bromide salt. The filtrate was concentrated in vacuo to a volume 200 mL, reheated at 60 °C for two hours, cooled to room temperatore, and filtered again. The filtrate was concentrated in vacuo to a volume 100 mL, reheated at 60 °C for another two hours, cooled to room temperatore, and concentrated in vacuo to provide a pale yellow solid. All of the solid material was combined, dissolved in 500 mL of methanol, and warmed to 60 °C. After two hours, the solution was reconcentrated in vacuo to provide a white solid which was triturated with hexane to remove soluble materials. Removal of residual solvents in vacuo provided the titled product hydrobromide as a white solid which was used in the next step without further purification. Step D: l-(4-CyanobenzyP-5-(hydroxymethyl)imidazole To a solution of the acetate from Step C (50.4 g) in 1.5 L of 3:1 THF/water at 0 °C was added lithium hydroxide monohydrate (18.9 g). After one hour, the reaction was concentrated in vacuo, diluted with EtOAc (3 L), and washed with water, sat. aq. NaHCθ3 and brine. The solution was then dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the cmde product as a pale yellow fluffy solid which was sufficiently pure for use in the next step without further purification. Step E: l-(4-Cyanobenzyl)-5-imidazolecarboxaldehyde To a solution of the alcohol from Step D (21.5 g) in 500 mL of DMSO at room temperatore was added triethylamine (56 mL), then Sθ3-pyridine complex (40.5 g). After 45 minutes, the reaction was poured into 2.5 L of EtOAc, washed with water (4 x 1 L) and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the titled aldehyde as a white powder which was sufficiently pure for use in the next step without further purification. Step F: N-Methoxy-N-methyl-2(S)-(t-butoxycarbonylamino)- hexanamide 3(S)-Butoxycarbonylaminohexanoic acid (24.6 g, 0.106 mol), N,0-dimethylhydroxylamine hydrochloride (15.5 g, 0.15 mol), EDC hydrochloride ( 22.3 g, 0.117 mol) and HOBT (14.3 g, 0.106 mol) were stirred in dry, degassed DMF (300 mL) at 20°C under nitrogen. N- Methylmoφholine was added to obtain pH 7. The reaction was stirred overnight, the DMF distilled under high vacuum, and the residue partitioned between ethyl acetate and 2% potassium hydrogen suifate. The organic phase was washed with satorated sodium bicarbonate, water, and satorated brine, and dried with magnesium suifate. The solvent was removed in vacuo to give the title compound. Step G: 2(S)-(fe^Butoxycarbonylamino)hexanal A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45°C under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperatore below -35°C. When the addition was complete, the reaction was warmed to 5°C, then recooled to -45°C. A solution of potassium hydrogen suifate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperatore below -5°C. After quenching, the reaction was stirred at room temperature for lh. The mixtore was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen suifate. After washing with satorated brine, drying over magnesium suifate and solvent removal, the title compound was obtained. Step H: N-(2,3-Dimethylphenyl)-2(S)-(te7τ butoxycarbonylamino)hexanamine 2,3-Dimethylaniline (8.32 mL, 68.3 mmol) was dissolved in dichloroethane under nitrogen. Acetic acid was added to obtain pH 5, and sodium triacetoxyborohydride (17.2 g, 80.8 mmol) and cmshed molecular sieves (4 g) were added. A solution of the product from Step B (13.3 g, 62.1 mmol) in dichloroethane (80 mL) was added slowly dropwise at 20°C. The reaction was stirred overnight, then quenched with satorated sodium bicarbonate solution. The aqueous layer was removed, the organic phase washed with satorated brine and dried over magnesium suifate. Crystallization from hexane gave the title compound. Step I: 2(S)-(ter^Butoxycarbonylaπuno)-l-[N-(2,3- dimethylphenyPacetamidolhexane To a solution of the product of Step H (500 mg, 1.56 mmol) and triethylamine (0.240 mL, 1.72 mmol) in 10 mL of dichloromethane at 0 °C was added acetyl chloride (0.122 mL, 1.72 mmol). After 20 min, the solution was warmed to room temperature, then stirred another 2 hours. The reaction was poured into CH2C12, washed with 10% citric acid and brine, dried (Na2S04), filtered, and concentrated in vacuo to provide the titled product. Step J: (S)-2-[( 1 -(4-Cyanobenzyl)-5-imidazolylmethyl)amino]- 1 - r(2.3-dimethylphenyl)amino1hexane Through a solution of the product from Step I (533 mg, 1.47 mmol) in 20 mL of EtOAc at 0 °C was bubbled HCl gas. The satorated solution was warmed to room temperature and stirred for 40 minutes, then concentrated in vacuo. To a solution of this amine salt in 6 mL of 1:1 MeOH/THF at 0 °C was added the aldehyde from Step E (325 mg, 1.54 mmol) and 0.05 mL of acetic acid. After one hour, sodium cyanoborohydride was added (97 mg, 1.54 mmol), and the solution was allowed to warm to room temperatore overnight. After -16 hours, the reaction was poured into EtOAc, washed with sat. aq. NaHCθ3 and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo. The resulting product was purified by silica gel chromatography (1-2% MeOH/CHCl3). A portion of this was taken up in EtOAc/Et2θ and treated with excess HCl gas, then stripped to provide the titled compound. FAB mass spectmm m/e 458 (M+l). Analysis calculated for C28H35N5O • 2.0 HCl: C, 63.39; H, 7.03; N, 13.20; Found: C, 63.03; H, 6.97; N, 12.92. EXAMPLE 125 (S)-2-[N-(l-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(methyl)amino]-l- N-(2.3-dimethylphenyl)acetamidolhexane hydrochloride To a solution of the product from Step J of Example 124 (186 mg, 0.41 mmol) and formaldehyde (0.158 mL, 37% in H2O, 2.1 mmol) in 2 mL of acetonitrile was added sodium cyanoborohydride (41 mg, 0.66 mmol). The pH of the solution was adjusted to 5-7 by dropwise addition of AcOH. After 4 hours, another portion of sodium cyanoborohydride was added (30 mg), and the reaction was stirred overnight. The reaction was poured into EtOAc, washed with sat. aq. NaHCθ3 and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo. The resulting product was purified by silica gel chromatography (EtOAc, then 10% MeOH/CHCl3). A portion of this was taken up in EtOAc/Et2θ and treated with excess HCl gas, then stripped to provide the titled compound. FAB mass spectmm m/e 472 (M+l). Analysis calculated for C29H37N5O • 2.0 HCl: C, 58.50; H, 6.88; N, 11.62; Found: C, 58.53; H, 7.52; N, 11.53. EXAMPLE 126 N-[l-(4-cyanobenzyl)-5-iι ^azolylmethyl]-N'-(3- chlorophenyPethylenediamine hydrochloride Step A: N-(2-aminoethyl)-3-chloroaniline hydrochloride To a solution of 3-chloroaniline (30 mL) in 500 mL of dichloromethane at 0 °C was added dropwise a solution of 4 N HCl in 1,4-dioxane (80 mL). The solution was warmed to room temperatore, then concentrated to dryness in vacuo to provide a white powder. A mixtore of this powder with 2-oxazolidinone (24.6 g) was heated under nitrogen atmosphere at 160 °C for 10 hours, during which the solids melted, and gas evolution was observed. The reaction was allowed to cool, forming the titled compound as a pale brown solid. Step B: N- [ 1 -(4-cyanobenzyl)-5-imidazolylmethyl]-N'-(3- chlorophenyPethylenediamine The amine hydrochloride from Step A (978 mg) was partitioned between dilute aqueous NaHCθ3 solution and methylene chloride. The aqueous layer was washed with three portions of CH2CI2, and the combined organics were dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the free amine. To a solution of the amine in 11 mL of 1,2-dichloroethane at 0 °C was added 4 A powdered molecular sieves (2 g), followed by sodium triacetoxyborohydride (3.04 g). The aldehyde from Step E of Example 1 (1.21 g) was added, and the reaction was stirred at 0 °C. After 15 hours, , the reaction was poured into EtOAc, washed with sat. aq. NaHCθ3 , and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried (Na2S04), filtered, and concentrated in vacuo. The resulting product was taken up in 60 mL of 5: 1 benzene:CH2θ2, and propylamine (10 mL) was added. The reaction was stirred for 12 hours, then concentrated in vacuo, and purified by silica gel chromatography (5% MeOH/CHCl3) to provide the titled compound as a white foam. A portion of this was taken up in CH2CI2 and treated with excess HCl/Et2θ, then stripped to provide the titled compound. FAB mass spectmm m/e 366 (M+l). Analysis calculated for C20H20N5CI • 2.70 HCl: C, 51.77; H, 4.93; N, 15.09; Found: C, 51.81; H, 4.96; N, 13.43. EXAMPLE 127 l-(4-Cyanobenzyl)-5-[N-(3-phenylpropyl)aminomethyl] imidazole hydrochloride The titled compound was prepared from from the aldehyde product from Step E of Example 124 and 3-phenylpropylamine using the procedure described in Step B of Example 126. FAB mass spectrum m/e 331 (M+l). Analysis calculated for C21H22N4 • 2.10 HCl • 0.80 H2O: C, 59.86; H, 6.15; N, 13.30; Found: C, 59.97; H, 6.18; N, 13.09. EXAMPLE 128 (S)-2-[(l-(4-Cyanobenzyl)-5-imidazolylmethyl)amino]-N- (benzyloxycarbonyl)-N-(3-chlorobenzyl)-4-(methanesulfonyl)butanamine hydrochloride Step A: (S)-2-(tert-Butoxycarbonylamino)-N-methoxy-N-methyl- 4- (methylthio)butanamide (30.0 g, 0.120 mol), N,0- dimethylhydroxylamine hydrochloride (14.1 g, 0.144 mol), EDC hydrochloride (27.7 g, 0.144 mol) and HOBT (19.5 g, 0.144 mol) were stirred in dry DMF (300 mL) at 20°C under nitrogen. More N,0- dimethylhydroxylamine hydrochloride (2.3 g, 23 mmol) was added to obtain pH 7-8. The reaction was stirred overnight, the DMF distilled to half the original volume under high vacuum, and the residue partitioned between ethyl acetate and sat. NaHCθ3 soln. The organic phase was washed with satorated sodium bicarbonate, water, 10% citric acid, and brine, and dried with sodium suifate. The solvent was removed in vacuo to give the titled compound. Step B: (S)-2-(tø^Butoxycarbonylaιm^o)-N-metooxy-N-methyl-4- (methanesulfonyPbutanamide To solution of the product from Step A (23.1 g, 79.2 mmol) in methanol (300 mL) at 0 °C was added a suspension of magnesium monoperoxyphthalate (117 g, 238 mmol) in 500 mL MeOH. The reaction was allowed to warm to room temperatore. After 16 hours, the reaction was quenched at 0 °C by the addition of 2N Na2S2θ3 soln. The solution was poured into EtOAc and sat NaHCθ3 solution, and the organic layer was washed with brine, dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the cmde titled compound. Step C: (S)-2-(tert-Butoxycarbonylamino)-4- (methanesulfonvPbutanal A suspension of lithium aluminum hydride (5.15 g, 0.136 mol) in ether (290 mL) was stirred at room temperature for one hour. The solution was cooled to -75 °C under nitrogen, and a solution of the product from Step B (23.9 g, 73.6 mol) in THF (60 mL) was added over ca. 30 min, maintaining the temperatore below -40 °C. When the addition was complete, the reaction was warmed to -15 °C, then recooled to -35 °C. A solution of potassium hydrogen suifate (19.4 g) in 77 mL water was slowly added. The mixture was warmed to room temperatore, and stirred for one hour. The solution was filtered through a pad of celite, washed with 10% HCl solution, sat. NaHCθ3 solution and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the titled aldehyde. Step D: (S)-2-(tert-butoxycarbonylamino)-N-(3-chlorobenzyl)-4- (methanesulfonyPbutanamine To a solution of 3-chlorobenzylamine (0.628 mL, 5.14 mmol) and cmshed molecular sieves (1.5 g) in dichloroethane (10 mL) under nitrogen at 0 °C was added sodium triacetoxyborohydride (2.73 g, 12.9 mmol), followed the product from Step C (2.73 g, 5.14 mmol). The reaction was stirred overnight, allowing it to warm to room temperatore. The solution was poured into EtOAc and sat NaHC03 solution, and the organic layer was washed with brine, dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the cmde product which was purified by silica gel chromatography (2.5-5% MeOH/CHCl3) to obtain the titled compound as a white foam. Step E: (S)-2-(tert-Butoxycarbonylamino)-N- (benzyloxycarbonyl)-N-(3-chlorobenzyl)-4- (methanesulfonvPbutanamine To a solution of the amine from Step D (754 mg, 1.93 mmol) and triethylamine (0.403 mL, 2.89 mmol) in 5 mL of dichloromethane at 0 °C was added benzylchloroformate (0.303 mL, 2.12 mmol). ter 2 hours, the solution was poured into EtOAc and sat NH4CI solution, and the organic layer was washed with sat. NaHCθ3 soln. and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the cmde product which was purified by silica gel chromatography (30-40% EtOAc/hexane) to obtain the titled compound as a white foam. Step F: (S)-2-[(l-(4-cyanobenzyl)-5-imidazolylmethyl)amino]-N- (benzyloxycarbonyl)-N-(3-chlorobenzyl)-4- (methanesulfonvPbutanamine To a solution of the product from Step E (360 mg, 0.686 mmol) in 6 mL of dichloromethane was added at room temperatore dropwise 3 mL of trifluoroacetic acid. After 30 minutes, the solution was concentrated in vacuo. The resulting product was reconcentrated from benzene three times to remove excess trifluoroacetic acid. To a solution of the amine salt in 4.2 mL of 1,2-dichloroethane at 0 °C was added 4A powdered molecular sieves, followed by sodium triacetoxyborohydride (363 mg, 1.71 mmol). The aldehyde from Step E of Example 1 (159 mg, 0.754 mmol) was added at 0 °C, followed by N-methylmoφholine (0.076 mL, 0.69 mmol). The reaction was stirred overnight, allowing it to warm to room temperatore. The reaction was poured into EtOAc, washed with sat. aq. NaHC03 and brine, dried (Na2Sθ4), filtered, and concentrated in vacuo. The resulting product was purified by silica gel chromatography (50-75% acetone/hexane) to provide the desired product . A portion of this was taken up in CH2CI2 and treated with excess HCl/Et2θ, then stripped to provide the titled compound. FAB mass spectmm m/e 620 (M+l). Analysis calculated for C32H34N5O4SCI • 2.0 HCl • 0.30 H2O C, 55.03; H, 5.28; N, 10.03; Found: C, 55.00; H, 5.42; N, 9.99. EXAMPLE 129 In vitro inhibition of ras famesyl transferase Assays of famesyl-protein transferase. Partially purified bovine FPTase and Ras peptides (Ras-CVLS, Ras-CVIM and RAS-CAIL) were prepared as described by Schaber et al, J. Biol Chem. 265:14701-14704 (1990), Pompliano, et al, Biochemistry 57:3800 (1992) and Gibbs et al, PNAS U.S.A. §6:6630-6634 (1989), respectively. Bovine FPTase was assayed in a volume of 100 μl containing 100 mM 7V-(2-hydroxy ethyl) piρerazine-N'-(2-ethane sulfonic acid) (HEPES), pH 7.4, 5 mM MgCl2, 5 mM dithiothreitol (DTT), 100 mM [3H]-farnesyl diphosphate ([SHI"! 7 ??; 740 CBq/mmol, New England Nuclear), 650 nM Ras-CVLS and 10 μg/ml FPTase at 31°C for 60 min. Reactions were initiated with FPTase and stopped with 1 ml of 1.0 M HCL in ethanol. Precipitates were collected onto filter-mats using a TomTec Mach II cell harvestor, washed with 100% ethanol, dried and counted in an LKB β-plate counter. The assay was linear with respect to both substrates, FPTase levels and time; less than 10% of the [3H]-FPP was utilized during the reaction period. Purified compounds were dissolved in 100% dimethyl sulfoxide (DMSO) and were diluted 20-fold into the assay. Percentage inhibition is measured by the amount of incoφoration of radioactivity in the presence of the test compound when compared to the amount of incoφoration in the absence of the test compound. Human FPTase was prepared as described by Omer et al., Biochemistry 32:5167-5176 (1993). Human FPTase activity was assayed as described above with the exception that 0.1% (w/v) polyethylene glycol 20,000, 10 μM ZnCl 2 and 100 nM Ras-CVIM were added to the reaction mixtore. Reactions were performed for 30 min., stopped with 100 μl of 30% (v/v) trichloroacetic acid (TCA) in ethanol and processed as described above for the bovine enzyme. The compounds of the instant invention described in Examples 1-128 were tested for inhibitory activity against human FPTase by the assay described above and were found to have IC50 of < 50 μM. EXAMPLE 130 In vivo ras famesylation assay The cell line used in this assay is a v-ras line derived from either Ratl or NIH3T3 cells, which expressed viral Ha-ras p21. The assay is performed essentially as described in DeClue, J.E. et al, Cancer Research 51:112-111, (1991). Cells in 10 cm dishes at 50-75% confluency are treated with the test compound (final concentration of solvent, methanol or dimethyl sulfoxide, is 0.1%). After 4 hours at 37°C, the cells are labelled in 3 ml methionine-free DMEM supple-meted with 10% regular DMEM, 2% fetal bovine semm and 400 mCi[35S]methionine (1000 Ci/mmol). ter an additional 20 hours, the cells are lysed in 1 ml lysis buffer (1% NP40/20 mM HEPES, pH 7.5/5 mM MgCl2/lmM DTT/10 mg/ml aprotinen/2 mg/ml leupeptin/2 mg/ml antipain/0.5 mM PMSF) and the lysates cleared by centrifugation at 100,000 x g for 45 min. Aliquots of lysates containing equal numbers of acid-precipitable counts are bought to 1 ml with IP buffer (lysis buffer lacking DTT) and immunoprecipitated with the ras-specific monoclonal antibody Y13-259 (Furth, M.E. et al, J. Virol 43:294-304, (1982)). Following a 2 hour antibody incubation at 4°C, 200 ml of a 25% suspension of protein A-Sepharose coated with rabbit anti rat IgG is added for 45 min. The immunoprecipitates are washed four times with IP buffer (20 nM HEPES, pH 7.5/1 mM EDTA/1% Triton X-100.0.5% deoxycholate/0.1%/SDS/0.1 M NaCl) boiled in SDS-PAGE sample buffer and loaded on 13% acrylamide gels. When the dye front reached the bottom, the gel is fixed, soaked in Enlightening, dried and autoradiographed. The intensities of the bands corresponding to farnesylated and nonfamesylated ras proteins are compared to determine the percent inhibition of famesyl transfer to protein. EXAMPLE 131 In vivo growth inhibition assay To determine the biological consequences of FPTase inhibition, the effect of the compounds of the instant invention on the anchorage-independent growth of Rat 1 cells transformed with either a v- ras, v-raf, or v-mos oncogene is tested. Cells transformed by v-Raf and v-Mos maybe included in the analysis to evaluate the specificity of instant compounds for Ras-induced cell transformation. Rat 1 cells transformed with either v-ras, v-raf, or v-mos are seeded at a density of 1 x 10 4 cells per plate (35 mm in diameter) in a 0.3% top agarose layer in medium A (Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine semm) over a bottom agarose layer (0.6%). Both layers contain 0.1% methanol or an appropriate concentration of the instant compound (dissolved in methanol at 1000 times the final concentration used in the assay). The cells are fed twice weekly with 0.5 ml of medium A containing 0.1% methanol or the concentration of the instant compound. Photomicrographs are taken 16 days after the cultures are seeded and comparisons are made.

Claims: WHAT IS CLAIMED IS: 1. A compound which inhibits Ras farnesyl-transferase having the Formula I: wherein: Rla is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2- C20 alkynyl, Rl O-, RHs(0) m -, R 10 C(O)NRl0-, CN, Nθ2, (R!0)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO)2, or RllOC(O)NRl0-, c) C 1 -C6 alkyl unsubstitoted or substitoted by aryl, heterocyclic, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, RlOO-, RllS(0) m -, R 10 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lθC(O)-NRl - ; R!^ is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2-C20 alkenyl, C2-C20 alkynyl, Rl O-, RllS(0) m -, CN, N02, (R 10 )2N-C(NRlO)-, Rl C(O)-, RlOθC(O)-, N3 or -N(RlO) 2 , c) C1-C6 alkyl unsubstitoted or substitoted by substitoted or unsubstitoted aryl, substitoted or unsubstitoted heterocyclic, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, RlOo-, RllS(0)m-, CN, (R10) 2 N-C(NR10)-, RlOc(O)-, RlOθC(O)-, N3 or -N(RlO)2; R2 and R are independently selected from: a) a side chain of a natorally occurring amino acid, b) an oxidized form of a side chain of a natorally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substitoted or unsubstitoted C1-C20 alkyl, substitoted or unsubstitoted C2-C20 alkenyl, substitoted or unsubstitoted C3-C10 cycloalkyl, substitoted or unsubstitoted aryl or substitoted or unsubstitoted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, R 10 O-, Rl l S(0) m -, R10C(O)NR10-, CN, (Rl ) 2 N-C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, RUθC(O)NRl0- and C1-C2O alkyl, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R are combined to form - (CH2)s - ; or R2 or R3 are combined with R7 to form a ring such that R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substitoted by C2-C2O alkenyl, RIOO-, Rl lS(0)m-. R 10 C(O)NRl -, CN, N3, (RlO)2N- C(NRlO)-, RlOc(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) unsubstitoted or substitoted aryl, unsubstituted or substitoted heterocycle, C3-C10 cycloalkyl, C2- C20 alkenyl, halogen, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N02, (R 10 )2N-C(NRlO)-, RlOC(O)-, N3, -N(Rl )2, or Rl 10C(0)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; Rl3a and R 13b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substitoted by C2-C2O alkenyl, RlOO-, Rl lS(0)m-, R 10 C(O)NRl0_, CN, N3, (R 10 )2N- C(NRl )-, RlOC(O)-, -N(Rl )2, or Rl 10C(0)NR10-, c) unsubstitoted or substituted aryl, unsubstituted or substitoted heterocycle, C3-C10 cycloalkyl, C2- C20 alkenyl, halogen, Rl4θ-, RHS(0) m -, Rl0C(O)NRl0-, CN, N02, (R 10 )2N-C(NRl )-, R10C(O)-, N3, -N(Rl )2, or Rl 10C(0)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, C1-C2O perfluoroalkyl, allyloxy, F, Cl, Br, RlOO-, R π S(0)m-, R 10 C(O)NRl0-, CN, NO2, Rl0 2 N-C(NRl )-, RlOC(O)-, N3, -N(RlO) 2 , (Rl2) 2 NC(0)- or RHθC(0)NRl -, and c) C1-C6 alkyl unsubstitoted or substitoted by substitoted or unsubstituted aryl, substitoted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C20 alkynyl, C2- C20 perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R7 is independently selected from a) hydrogen, b) unsubstitoted or substitoted aryl, c) unsubstitoted or substituted heterocycle, d) unsubstitoted or substituted C3-C10 cycloalkyl, and e) C1-C6 alkyl substitoted with hydrogen or an unsubstitoted or substitoted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R8 is selected from: a) hydrogen, b) substitoted or unsubstitoted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2-C2O alkenyl, C2-C2O alkynyl, C1-C20 perfluoroalkyl, allyloxy, F, Cl, Br, RlOO-, R π S(0) m -, R 10 C(O)NRl0-, -S(O)2NRl0 2 , CN, NO2, Rlθ2N-C(NRl )-, RlOc(O)-, R10OC(O)-, N3, -N(RlO) 2 , or RHθC(O)NRl0-, and c) C1-C6 alkyl unsubstitoted or substitoted by substituted or unsubstitoted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2-C20 alkenyl, C2-C2O alkynyl, C2- C20 perfluoroalkyl, F, Cl, Br, RlOO, Rl lS(0) m -, Rl C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, Rl θC(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C20 alkenyl, C2-C20 alkynyl, C2-C20 perfluoroalkyl, F, Cl, Br, RlOO-, RllS(0) m -, R 10 C(O)NRl -, CN, N02, (RlO)2N-C-(NRlO)-, RlOC(0)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, and c) C1-C6 alkyl unsubstitoted or substitoted by C2-C20 perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Ri0C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO)2, or RHOC(O)NR10- ; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; RU is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (R12) 2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkyl substitoted with CO2R 1 °, C 1 -C6 alkyl substitoted with aryl, C 1 - C6 alkyl substitoted with substitoted aryl, C1-C6 alkyl substitoted with heterocycle, C1-C6 alkyl substitoted with substitoted heterocycle, aryl and substitoted aryl; A- A- and A3 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, O, -N(R7)-, -S(0)2N(R7)-, -N(R7)S(0)2-, or S(0) m ; A4 is selected from: a bond, O, -N(R7)- or S, V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C 1 -C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A 1 is S(0) m and V is not hydrogen if Al is a bond, n is 0 and A-2 is S(0)m; W is a heterocycle; Z is independently Rl a 2 or O; or a pharmaceutically acceptable salt thereof. 2. The compound according to Claim 1 of the formula I: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, RlOO-, -N(R O)2 or C2-C6 alkenyl, and c) C1-C6 alkyl unsubstitoted or substituted by substitoted or unsubstitoted aryl, substitoted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, Rl O-, or -N(RlO)2; R2 and R3 are independently selected from: a) a side chain of a natorally occurring amino acid, b) an oxidized form of a side chain of a natorally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substitoted or unsubstitoted Cl-ClO alkyl, substitoted or unsubstitoted C2-C10 alkenyl, substitoted or unsubstitoted C3-C10 cycloalkyl, substitoted or unsubstituted aryl or substitoted or unsubstitoted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, R 10 O-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO)2, R110C(0)NR10- and C1-C2O alkyl, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocycle and C3- ClO cycloalkyl; wherein said substitoted group is substitoted with 1 or 2 substitotents selected from: F, Cl, Br, CF3, NH2, N(Cl-C6 alkyl)2, Nθ2, CN, (C1-C6 alkyl)0-, -OH, (C1-C6 alkyl)S(0)m-, (C1-C6 alkyl)C(0)NH-, H2N-C(NH)-, (Cl- C6 alkyl)C(O)-, (C1-C6 alkyl)OC(O)-, N3 C1-C6 alkyl)OC(0)NH- and C1-C2O alkyl; or R2 or R3 are combined with R7 to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstituted or substitoted by C2-C6 alkenyl, Rl O-, Rl lS(0)m-, Rl 0 C(O)NRl0-, CN, N3, (RlO)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) substitoted or unsubstituted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, halogen, Rl O-, RllS(0) m -, Rl0C(O)NRl0-, CN, N02, (RlO)2N-(NRlO)-, Rl C(O)-, N3, -N(Rl )2, or Rl 10C(0)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; Rl3a and Rl3b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substituted by C2-C6 alkenyl, RlOO-, R lS(0)πr, R1°C(0)NR10-, CN, N3, (Rl°)2N- C(NRl )-, RlOC(O)-, -N(Rl )2, or R! 1OC(O)NR10-, c) substitoted or unsubstitoted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, halogen, Rl4θ-, RHS(0) m -, RlOC(0)NRlO-, CN, N02, (R10)2N-(NR10)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstituted heterocycle, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl O-, allyloxy, Rl0C(O)NRl0-, CN, N02, (R1°)2N-C(NR10)-, RlOc(O)-, -N(RlO)2, (Rl2) 2 NC(0)- or R11OC(O)NR1 -, and c) C l -C6 alkyl substitoted by C 1 -C6 perfluoroalkyl, R 10θ-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOc(O)-, -N(Rl )2, OΓ RHOC(O)NR10-; R7 is independently selected from a) hydrogen, b) unsubstitoted or substitoted aryl, c) unsubstituted or substitoted heterocycle, d) unsubstituted or substitoted C3-C10 cycloalkyl, and e) C1-C6 alkyl substitoted with hydrogen or an unsubstitoted or substitoted group selected from aryl, heterocycle and C3- ClO cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR10-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RHθC(O)NRl0-, and c) C 1 -C6 alkyl substitoted by C 1 -C6 perfluoroalkyl, R 1 OO-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or R11OC(O)NR1 - ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C 1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl ls(0)m-, R!°C(O)NR10-, CN, NO2, (Rl°)2N- C(NRl )-, Rl0c(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C l -C6 alkyl unsubstituted or substitoted by C l -C6 perfluoroalkyl, F, Cl, Rl O-, RHS(0) m -, R1°C(0)NR10-, CN, (RlO) 2 N-C(NRl )-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; R 2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl2) 2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkyl substitoted with Cθ2Rl°, C1-C6 alkyl substitoted with aryl, Cl- C6 alkyl substitoted with substitoted aryl, C1-C6 alkyl substitoted with heterocycle, C1-C6 alkyl substitoted with substitoted heterocycle, aryl and substitoted aryl; Al, A2 and A3 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A is selected from: a bond, O, -N(R 7 )- or S; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, and provided that V is not hydrogen if A 1 is S(0) m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, oxazolyl, isoxazolyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently R 1 a 2 or O ; or a pharmaceutically acceptable salt thereof. 3. The compound according to Claim 1 of the formula I: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstituted heterocycle, C3-C10 cycloalkyl, RlOO- or C2-C6 alkenyl, c) C 1 -C6 alkyl unsubstitoted or substitoted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO-, or R2 and R3 are independently selected from: a) a side chain of a natorally occurring amino acid, b) an oxidized form of a side chain of a natorally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substitoted or unsubstituted Cl-ClO alkyl, substitoted or unsubstitoted C2-C10 alkenyl, substitoted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substitoted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, RlOO-, RllS(0)m-, R1°C(0)NR10-, CN, (RlO)2N- C(NRl°)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, Rl lθC(O)NRl0- and C1-C2O alkyl; or R2 or R3 are combined with R to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substitoted by C2-C6 alkenyl, Rl°0-, Rl lS(0) m -, R1 C(O)NR10-, CN, N3, (RlO)2N- C(NRlO)-, RlOC(O)-, -N(Rl )2, or Rl lθC(O)NRl -, c) substitoted or unsubstituted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, RlOO-, RHS(0) m -, Rl C(0)NRlO-, CN, N02, (Rl°)2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or Rl 10C(0)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from substitoted or unsubstitoted aryl, substitoted or unsubstituted heterocyclic and C3-C10 cycloalkyl; Rl3a and Rl3b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substitoted by C2-C6 alkenyl, RlOO-, Rl lS(0)m-, R1°C(0)NR10-, CN, N3, (Rl°)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl 10C(0)NR10-, c) substitoted or unsubstitoted aryl, substituted or unsubstituted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, R 4θ-, RHS(0) m -, R10C(O)NR10-, CN, N02, (Rl°)2N-C(NRl )-, RlOC(O)-, N3, -N(RlO)2, or RUOC(O)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from substitoted or unsubstitoted aryl, substitoted or unsubstituted heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstitoted heterocycle, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, allyloxy, Rl0C(O)NRl0-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, -N(RlO)2, (Rl2)2NC(0)- or RHOC(O)NR10-, and c) C 1 -C6 alkyl substitoted by C 1 -C6 perfluoroalkyl, R 1 OO-, Rl0C(O)NRl0-, (R10) 2 N-C(NR10)-, RlOC(O)-, -N(RlO)2, or RllOC(O)NRl0-; R7 is independently selected from a) hydrogen, b) unsubstitoted or substitoted aryl, c) unsubstituted or substitoted heterocycle, d) unsubstitoted or substitoted cycloalkyl, and e) C1-C6 alkyl substitoted with hydrogen or an unsubstitoted or substituted group selected from aryl, heterocycle and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1 -C6 perfluoroalkyl, F, Cl, RlOO-, R 0C(O)NR1 -, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RHθC(0)NRlO-, and c) C 1 -C6 alkyl substitoted by C 1 -C6 perfluoroalkyl, R 1 OO-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RHOC(O)NR10-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C 1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, Nθ2, (Rl°)2N- C(NRlO)-, Rl0c(O)-, RlOθC(O)-, -N(RlO) 2 , or RllθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substitoted by C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, RHS(0) m -, R10C(O)NR10-, CN, (RlO)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, -N(RlO)2, or RHθC(O)NRl0-; RlO is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen, C1-C6 alkyl and aryl, or (Rl2)2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, Cl-C6 alkyl, Cl-C6 alkyl substitoted with Cθ2Rl°, Cl-C6 alkyl substitoted with aryl, Cl- C6 alkyl substitoted with substitoted aryl, C1-C6 alkyl substituted with heterocycle, C1-C6 alkyl substituted with substitoted heterocycle, aryl and substitoted aryl; A and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A4 is selected from: a bond, O, -N(R7)- or S; A is selected from: a bond, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently R a 2 or O; or a pharmaceutically acceptable salt thereof. 4. The compound according to Claim 1 of the formula I: ia wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) substitoted or unsubstituted aryl, substitoted or unsubstituted heterocycle, C3-C10 cycloalkyl, RlOO- or C2-C6 alkenyl, c) C1-C6 alkyl unsubstitoted or substitoted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO-, or R2 and R3 are independently selected from: a) a side chain of a natorally occurring amino acid, b) an oxidized form of a side chain of a natorally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substitoted or unsubstituted Cl-ClO alkyl, substitoted or unsubstitoted C2-C10 alkenyl, substitoted or unsubstituted C3-C10 cycloalkyl, substitoted or unsubstituted aryl or substitoted or unsubstituted heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, RlOO-, RllS(0)m-, R1°C(0)NR10-, CN, (Rl ) 2 N- C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0- and C1-C20 alkyl; or R2 or R3 are combined with R7 to form a ring such that: R4 and R5 are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substituted by C2-C6 alkenyl, RlOO-, Rl lS(0)m-, R1°C(0)NR1 -, CN, N3, (Rl°)2N- C(NRl )-, RlOC(O)-, -N(RlO)2, or RHOC(O)NR10-, c) substitoted or unsubstitoted aryl, substituted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, RlOO-, RHS(0) m -, RlOC(0)NRlO-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substituted group selected from substitoted or unsubstitoted aryl, substitoted or unsubstitoted heterocyclic and C3-C10 cycloalkyl; Rl3a and R 13b are independently selected from: a) hydrogen, b) C1-C6 alkyl unsubstitoted or substitoted by C2-C alkenyl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, N3, (RlO)2N- C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl 10C(0)NR10-, c) substitoted or unsubstitoted aryl, substitoted or unsubstitoted heterocycle, C3-C10 cycloalkyl, C2- C6 alkenyl, fluoro, chloro, Rl 0-, RllS(0) m -, RlOC(0)NRlO-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, N3, -N(RlO)2, or RHOC(O)NR10-, and d) C1-C6 alkyl substitoted with an unsubstitoted or substitoted group selected from substitoted or unsubstitoted aryl, substituted or unsubstituted heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from: a) hydrogen, b) substituted or unsubstituted aryl, substitoted or unsubstituted heterocycle, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl O-, allyloxy, Rl0C(O)NRl0-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, -N(Rl )2, (Rl2) 2 NC(0)- or RHOC(O)NR10-, and c) C 1 -C6 alkyl substitoted by C l -C6 perfluoroalkyl, R 1 OO-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, -N(RlO)2, O Γ RHOC(O)NR1 - ; R7 is independently selected from a) hydrogen, b) unsubstitoted or substitoted aryl, c) unsubstitoted or substitoted heterocycle, d) unsubstituted or substitoted cycloalkyl, and e) C1-C6 alkyl substitoted with hydrogen or an unsubstitoted or substitoted group selected from aryl, heterocycle and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, R O-, R10C(O)NR10-, CN, Nθ2, (R1 ) 2 N-C(NR1 )-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl -, and c) C1-C6 alkyl substitoted by Cχ-C6 perfluoroalkyl, RlOO-, Rl C(O)NRl0-, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or R11OC(O)NR10-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C 1-C6 perfluoroalkyl, F, Cl, RIOO, Rl lS(0)m-, R1°C(0)NR10-, CN, Nθ2, (Rl°)2N- C(NRlO)-, RlOC(O)-, Rl θC(O)-, -N(R1 ) 2J or Rl lθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R1°C(0)NR10-, CN, (Rl )2N-C(NRlO)-, Rlθc(θ)-, R10OC(O)-, -N(RlO)2, OΓ RHOC(O)NR10- ; RlO is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl2 is independently selected from hydrogen, Cl-C6 alkyl and aryl, or (Rl2)2 forms - (CH2)s - ; Rl4 is independently selected from hydrogen, Cl-C6 alkyl, Cl-C6 alkyl substitoted with Cθ2Rl°, Cl-C6 alkyl substitoted with aryl, Cl- C6 alkyl substitoted with substitoted aryl, Cl-C6 alkyl substituted with heterocycle, Cl-C6 alkyl substitoted with substitoted heterocycle, aryl and substituted aryl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, -NR7S(0)2-, O, -N(R7)-, or S(0) m ; A4 is selected from: a bond, O, -N(R7)- or S; A3 is selected from: a bond, -C(0)NR7-, -NR7C(0)-, -S(0)2NR7-, V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; Z is independently Rl a 2 or O; or a pharmaceutically acceptable salt thereof. 5. A compound which inhibits famesyl-protein transferase which is: N- Allyloxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cy anobenzyl)- lH-imidazol-5-yl)acetyl}amino-3(S)- methylpentanamine N-Naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5- yl)acetyl}amino-3(S)- methyl pentanamine N-Methoxycarbonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5-yl)acetyl}amino-3(S)- methyl pentanamine N- Acetyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cy anobenzyl)- 1 H- imidazol-5-yl)acetyl }amino-3(S)-methylpentanamine N-Propionyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Methylsulfonyl-N-naphth-l-ylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Ethylsulfonyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cy anobenzyl)- 1 H- imidazol-5-yl)acetyl } amino-3(S)- methylpentanamine N-Methylaminocarbonyl-N-naphth- 1 -ylmethyl-2(S)- { ( l-(4- cyanobenzyl)-lH-imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-Propyl-N-naphth-l-ylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol- 5-yl)acetyl}amino-3(S)- methylpentanamine N-3-Chlorobenzyl-N-naphth- 1 -ylmethyl-2(S)- { ( 1 -(4-cy anobenzyl)- 1H- imidazol-5-yl)acetyl }amino-3(S)- methylpentanamine N-(2-Imidazolylmethyl )-N-naphth-l-ylmethyl-2(S)-{ (l-(4-cyanobenzyl)- lH-imidazol-5-yl)acetyl}amino-3(S)- methylpentanamine 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyl)amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyl)amino- N-methyl-N-benzyl propionamide 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(t- butoxycarbonyPamino- N-(2-methylbenzyl) propionamide 2(RS)-{ [l-(Naρhth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3-(t- butoxycarbonyl)amino- N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-methyl-N-benzyl propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(2-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- amino- N-(3-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(3-methylbenzyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- acetylamino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)- { [ 1 -(Naphth-2-ylmethyl)- lH-imidazol-5-yl)] acetyl } amino-3-(2- methylpropionyl)amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- (phenylacetyl)amino- N-(naphth- 1 -ylmethyl)propionamide 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)] acetyl }amino-3- (phenylacetyl)amino- N-methyl-N-benzyl) propionamide [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)]-N-butylacetamide [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)]- N-methyl-N-(3,3- diρhenylρropyl)acetamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N-methyl-N-benzyl propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyPamino - N-(naphth-l -ylmethyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yll acetyl} amino -3-amino N-methyl-N-benzyl- propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino N-(3-methylbenzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-amino N-(naphth-l -ylmethyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3- (phenylacetyl)amino - N-methyl-N-benzyl) propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3- (acetyl)amino - N-(naphth-l-yl methyl)propionamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(2- methylpropionyl)amino - N-(naphth-l -ylmethyl) propionamide 2(RS)- { [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl] acetyl } amino -3-(2- methylpropionyl)amino - N-(naphth-l -ylmethyl) propionamide N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylρentyl]-N-( 1 -naphthylmethyl)glycine isopropylamide N-[2(S)-([l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylρentyl]-N-( 1 -naρhthylmethyl)glycine piperidinylamide 2(RS)-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino -3-(t- butoxycarbonyl)amino - N- methyl-N-(naphth-l -ylmethyl) propionamide N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}- 2(S){N - methanesulfonyl-N'-(naphth- 1 -ylmethyl)aminomethyl } -pyrrolidine N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl)acetyl } - 2(S)- { N'-acetyl-N * - naphth- 1 -ylmethyl-aminomethyl } -pyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl } -2(S)- [ 1 (R)- 1-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)acetyl}-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxyjmethylpyrrolidine N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-[l(R)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-[l(S)-l-(3- chlorophenyl)- 1 -hydroxylmethylpyrrolidine N- { 5-(4-Cyanobenzyl)- 1 H-imidazol- 1 -yl)acetyl } -4(R)-hydroxy-2(S)- [1 (R)- l-(3-chlorophenyl)- 1 -hydroxylmethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)acetyl }-4(R)-hydroxy-2(S)- [ 1 (S)- 1 -(3-chloroρhenyl)- 1 -hydroxylmethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl}-4(R)-hydroxy-2(S)-[l(R)- l-(3-cMorophenyl)-l-hydroxy]methylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl}-4(R)-hydroxy-2(S)-[l(S)- 1 -(3-chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyll-4(R)-hydroxy-2(S)-[l(R)- 1 -(3-chlorophenyl)- 1 -hydroxylmethylpyrrolidine N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyl]-4(R)-hydroxy-2(S)-[l(S)- 1 -(3-chlorophenyl)- 1 -hydroxylmethylpyrrolidine N- [ 1 -(4-Cyanobenzyl)- 1 -imidazol-5-ylmethyll -4(R)-hydroxy-2(S)- [ 1 (R)- 1 -(3-chlorophenyl)- 1 -hydroxylmethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { l-(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl }-4(R)-hydroxy-2(S)- { - acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N' acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { l-(4-Cyanophenethyl)-lH-imidazol-5-yl-methyl-4(R)-hydroxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl-acetyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanopheneth- 1 -yl)- lH-imidazol-5-yl-acetyl-4(R)-methoxy- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH~imidazol-5-yl-ethyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-2(S)-{N , -acetyl-N'-3- chlorobenzyl-aminomethyljpyrrolidine N-{ l-(4-Cyanophenethyl)-lH~imidazol-5-yl-ethyl}-4(R)-methoxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl pyrrolidine N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl } -4(R)-benzyloxy-2(S { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl pyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazolacetyl } -4(R)-benzyloxy-2(S)- { N 1 - acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-5-imidazol-5-ylmethyl}-4(R)-(2- henylbenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylmethyl } -4(R)-(4- chlorobenzyloxy)-2(S)- { N'-acetyl-N * -3 - chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazolemethyl }-4(R)-(4-cyanobenzyloxy)- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazol-5-ylmethyl } -4(R)-(3- pyridylmethoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylmethyl } -4(R)-(phenoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl } -4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(R)-(acetyloxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl } -4(R)-(2- methylacetyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-4(R)-(acetyloxy)-2(S)- { N'-S-chlorobenzyl-N'-acetyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl}-4(S)-(phenoxy)-2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)-5-imidazolethyl } -4(S)-(phenoxy)-2(S)- { N'-acetyl- N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-4(S)-fluoro-2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5ylethyl-4(R)-(2-phenylbenzyloxy)- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-4(R)-(4- chlorobenzyloxy)-2(S)- { N'-acetyl-N'-3 - chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-(4- cyanobenzyloxy)-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylethyl}-4(R)-(3-pyridylmethoxy)- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethyl-pyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl}-2(S)-{N'-acetyl-N , -3- cyanobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl } - 2(S)- { N'-acetyl-N'-3- methoxybenzyl } aminomethylpyrrolidine. N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-3- trifluoromethylbenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2- methoxybenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl }-2(S)- { N * -acetyl-N * -2- trifluoromethylbenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl } -2(S)- { N'-acetyl-N'-(2,2- diphenylethyl) } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'- diphenylmethyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2- chlorobenzyl } aminomethylpyrrolidine N- { 2(R)-Methyl-2-(l-(4-Cyanobenzyl)- lH-imidazol-5-yl))acetyl }- 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 2(S)-Methyl-2-( 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl))acetyl } - 2(S)- { N'-acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- { l-(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl }-2(S)- { N'-acetyl-N'-4- chlorobenzy 1 } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}-2(S)-{N'-acetyl-N'-2,3- dichlorobenzyl } aminomethylpyrrolidine N-[l-(4-Cyanobenzyl)-lH-imidazol-5-yllacetyl-4(R)-benzyloxy-2(S)- { N'-acetyl-N'-naphth- 1 -ylmethyl } aminomethylpyrrolidine N-[l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl-4(R)-benzyloxy-proline naphth- 1 -ylmethylamide N- [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yllacetylproline naphth- 1 - ylmethylamide N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)-methoxy-2(S)-{N'- acetyl-N'-5,6,7,8-tetrahydronaphm-l-ylmethyl}aminomethylpyrrolidine N-{ l-(4-cyanobenzyl)-lH-imidazol-5-yl)acetyl-4(R)-benzyloxy-2(S)- {N'-acetyl-N'-5,56,7,8-tetrahydronaphth-l-ylmethyl}aminomethyl- pyrrolidine l-(4-Cyanobenzyl)-lH-imidazol-5-ylmethyl-2(S)-{N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- Allyloxycarbonyl-2(S)- { ( 1 -(4-Cyanobenzyl)- 1 H-imidazol-5- yl)acetyl } amino-3 (S)-methyl-pentanamine 2(S)-{(l-(4-Cyanobenzyl)-lH-imidazol-5-yl)acetyl}amino-3(S)-methyl- N-(naρhth-2-ylsulfonyl)-ρentanamine N- Acetyl-N-2-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- lH-imidazol-5- yl)acetyl}amino-3(S)-methyl-pentanamine N-Acetyl-N-3-chlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yl)acetyl } amino-3(S)-methyl-pentanamine N- Acetyl-N-4-chlorobenzyl-2(S)- { ( 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl)acetyl } amino-3(S)-methyl-pentanamine N-Acetyl-N-2,3-dichlorobenzyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol- 5-yl)acetyl } amino-3(S)-methyl-pentanamine N-Allyloxycarbonyl-N-naphth-l-ylmethyl-2(S)-{2(R,S)-methyl-2-(l-(4- cyanobenzyl)-lH-imidazol-5-yl)acetyl}amino-3(S)-methyl-pentanamine N-t-Butoxycarbonylaminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4- cyanobenzyl)- 1 H-imidazol-5-ylacetyl } amino-3 (S)-methylpentanamine N- Aminoacetyl-N-naphth- 1 -ylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H- imidazol-5-ylacetyl}amino-3(S)-methylpentanamine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)ethyl } -2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -yl)ethoxycarbonyl } -2(S)- { N'- acetyl-N'-3-chlorobenzyl } aminomethylpyrrolidine N- { 5-(4-Cyanobenzyl)- IH-imidazol- 1 -ylacetyl }-2(S)-{ N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)ethyl }-2(S)- { N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine N-{ l-(4-Cyanobenzyl)-lH-imidazol-5-yl)methyl}-2(S)-{N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine hydrochloride N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)acetyl } -2(S)- { N'-acetyl-N'-3- chlorophenyl } aminomethylpyrrolidine N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)-ylmethyll-(N-2- methylbenzyl)glycine N'-(3-chlorophenyl)amide l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl] pyrrolidin-2(S)- ylmethyll-(N-2-methylbenzyl)-glycine N'-(3-chlorophenylmethyl) amide N-[l-(3-[lH-Imidazol-4-yllpropionyl)-pyrrolidin-2(S)-ylmethyll-(N-2- methylbenzyl)-glycine N'-methyl-N'-(3-chlorophenyl) amide 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl] pyrrolidin-2(S)- ylmethyl} -(N-2-methylbenzyl)-gly cine N'-methyl-N'-(3- chlorophenylmethyl) amide (S)-2-[(l-(4-cyanobenzyl)-5-imidazolylmethyl)aminol-l-[N-(2,3- dimethylphenyl)acetamidolhexane (S)-2-[N-(l-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(methyl)aminol-l- [N-(2,3-dimethylphenyl)acetamido]hexane N- [ 1 -(4-cyanobenzyl)-5-imidazolylmethyl]-N'-(3- chlorophenyl)ethylenediamine l-(4-Cyanobenzyl)-5-[N-(3-phenylpropyl)aminomethyl] imidazole or (S)-2-[( 1 -(4-Cyanobenzyl)-5-imidazolylmethyl)amino]-N- (benzyloxycarbonyl)-N-(3-chlorobenzyl)-4-(methanesulfonyl)butanamine or a pharmaceutically acceptable salt or optical isomer thereof. 6. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N- Allyloxycarbonyl-N-naphthylmethyl-2(S)- { 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl)acetyl}amino-3(S)- methyl pentanamine or a pharmaceutically acceptable salt or optical isomer thereof. 7. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-Acetyl-N-naphthylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol-5- yl)acetyl } amino-3(S)-methyl pentanamine or a pharmaceutically acceptable salt or optical isomer thereof. 8. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-Propionyl-N-naphthylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH-imidazol- 5-yl)acetyl}amino-3(S)- methyl pentanamine or a pharmaceutically acceptable salt or optical isomer thereof. 9. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-Methylsulfonyl-N-naphthylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl } amino-3(S)- methyl pentanamine or a pharmaceutically acceptable salt or optical isomer thereof. 10. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-Ethylsulfonyl-N-naphthylmethyl-2(S)-{(l-(4-cyanobenzyl)-lH- imidazol-5-yl)acetyl}amino-3(S)- methyl pentanamine or a pharmaceutically acceptable salt or optical isomer thereof. 11. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: 2(RS)-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl)l acetyl }amino-3- (phenylacetyl)amino- N-methyl-N-benzyl) propionamide or a pharmaceutically acceptable salt or optical isomer thereof. 12. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycine piperidinylamide or a pharmaceutically acceptable salt or optical isomer thereof. 13. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N- { 1 -(4-cyanobenzyl)- lH-imidazol-5-yl)acetyl } - 2(S)- { N'-acetyl-N'- naphthylmethyl-aminomethyl } -pyrrolidine or a pharmaceutically acceptable salt thereof. 14. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-(2,3-Dimethylρhenyl)-N-methoxycarbonyl-2(S)-[4-cyanobenzyl-4- (imidazolylmethyl)amino]-3(S)-methylpentamine or a pharmaceutically acceptable salt or optical isomer thereof. 15. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-{5-(4-Cyanobenzyl)-lH-imidazol-l-yl)ethyl}-2(S)-[l(R)-l-(3- chlorophenyl)-l-hydroxy]methylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 16. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N- { 1 -(4-Cyanobenzyl)- 1 H-imidazol- 1 -ylethyl } -4(R)-hydroxy-2(S)- [ 1 (R)- l-(3-chlorophenyl)-l-hydroxy}methylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 17. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N-[5-(4-Cyanobenzyl)-lH-imidazol-l-ylethyll-4(R)-hydroxy-2(S)-[l(R)- l-(3-chlorophenyl)-l-hydroxylmethylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 18. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N{ l-(4-Cyanobenzyl)- lH-imidazol-5-ylethyl }-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 19. The compound according to Claim 5 which inhibits famesyl-protein transferase which is: N- { 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)methyl } -2(S)- { N'-acetyl-N'-3- chloropheny 1 } aminomethylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 20. The compound according to Claim 5 which inhibits famesyl-protein transferase which is : N- { 5-(4-Cyanobenzyl)- IH-imidazol- l-yl)ethyl }-2(S)- { N'-acetyl-N'-3- chlorobenzyl } aminomethylpyrrolidine or a pharmaceutically acceptable salt or optical isomer thereof. 21. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 1. 22. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 2. 23. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 5. 24. A method for inhibiting farnesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 21. 25. A method for inhibiting farnesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 22. 26. A method for inhibiting farnesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 23. 27. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21. 28. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 22. 29. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 23. 30. A method for treating or preventing a disease or condition in a mammal, the disease or condition which is selected from: a) a benign proliferative disorder component of NF-1; b) infection of hepatitis delta and related vimses; c) restenosis; d) polycystic kidney disease; and e) fungal infections; which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21.

Inventors: ANTHONY NEVILLE J, BERGMAN JEFFREY M, DESOLMS S JANE, DINSMORE CHRISTOPHER J, GOMEZ ROBERT P, MACTOUGH SUZANNE C, SOLINSKY KELLY M, WILLIAMS THERESA M, ANTHONY, NEVILLE, J., BERGMAN, JEFFREY, M., DESOLMS, S., JANE, DINSMORE, CHRISTOPHER, J., GOMEZ, ROBERT, P., MACTOUGH, SUZANNE, C., SOLINSKY, KELLY, M., WILLIAMS, THERESA, M.
Applicants: ANTHONY NEVILLE J, BERGMAN JEFFREY M, DESOLMS S JANE, DINSMORE CHRISTOPHER J, GOMEZ ROBERT P, MACTOUGH SUZANNE C, MERCK & CO INC, SOLINSKY KELLY M, WILLIAMS THERESA M, ANTHONY, NEVILLE, J., BERGMAN, JEFFREY, M., DESOLMS, S., JANE, DINSMORE, CHRISTOPHER, J., GOMEZ, ROBERT, P., MACTOUGH, SUZANNE, C., MERCK & CO., INC., SOLINSKY, KELLY, M., WILLIAMS, THERESA, M.
Application year: 1996
Main classification: A61K31
IPC codes: C07D233, C07D401