THIOL-FREE INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogs differ from those previously described as inhibitors of Ras farnesyl 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: THIOL-FREE INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE RELATED APPLICATIONS The present patent application is a continuation-in-part application of copending application Serial No. 08/314,974, filed September 29, 1994. 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 farnesyl-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. 67:355-386 (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-trans lational famesylation. Other farnesylated proteins include the Ras-related GTP-binding proteins such as Rho, fungal mating factors, the nuclear lamins, and the gamma subunit of transducin. James, et al., J. 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 farnesyl-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 farnesyl-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 farnesyl-protein transferase blocks the growth of ras- dependent tumors in nude mice (N.E. Kohl et al, Proc. Natl. Acad. Sci U.SΛ., 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 recently been shown that farnesyl-protein transferase inhibitors are inhibitors of proliferation of vascular smooth muscle cells and are therefore useful in the prevention and thereapy of arteriosclerosis and diabetic disturbance of blood vessels (JP H7- 112930). Indirect inhibition of farnesyl-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 famesyl pyrophosphate. Farnesyl-protein transferase utilizes famesyl pyrophosphate to covalently modify the Cys thiol group of the Ras CAAX box with a famesyl group (Reiss et al. Cell, 62:81-88 (1990); Schaber et al, J. Biol Chem., 265:14701 -14704 (1990); Schafer et al, Science, 249:1133-1139 (1990); Manne et al, Proc. Natl Acad. Sci USA, 57:7541-7545 (1990)). Inhibition of famesyl pyrophosphate biosynthesis by inhibiting HMG-CoA reductase blocks Ras membrane localization in cultured cells. However, direct inhibition of farnesyl-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 farnesyl-protein transferase (FPTase) have been described in two general classes. The first are analogs of famesyl 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, 55:732-736 (1991)). Such inhibitors may inhibit protein prenylation while serving as alternate substrates for the farnesyl-protein transferase enzyme, or may be purely competitive inhibitors (U.S. Patent 5,141 ,851 , University of Texas; N.E. Kohl et al, 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 is, therefore, an object of this invention to develop tetrapeptide-based compounds which do not have a thiol moiety, and which will inhibit famesyl transferase and the post-translational functionalization of the oncogene Ras protein. 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 analogs of the CAAX motif of the protein Ras that is modified by famesylation in vivo. These CAAX analogs inhibit the famesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras famesyl 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 famesyl transferase inhibitors and methods for their production. The compounds of this invention are illustrated by the formulae: and IV DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention inhibit the famesylation of Ras. In a first embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the formula I: wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0) m -, R10C(0)NR 0-, CN, N02, (RlO) 2 N-C(NRlO)-, Rl0c(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lθC(O)NRl0_, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0)m-, R!OC(0)NR 10., CN, (R10) 2 N-C(NR 10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, or R 1 1OC(O)NR1 - ; R2a and R2b 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 C 1 -C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl !S(0) m -, R10C(0)NR1 -, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl0)2, R 0C(0)NR10- and -C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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 Ci -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(Rl )2, Nθ2, Rl°0-, Rl l S(0) m -, R10C(0)NR1 -, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, R lOθC(O)-, N3, -N(R lO)2, Rl lOC(O)NRl0- and C1-C20 alkyl, and d) C1-Q5 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R3 and R4 are combined to form - (CH2)s - ; R5a and R5b 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 C1-C20 alkyl, C 2 -C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocycle group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, Rl°0-, Rl lS(0) m -, R !0C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl -, -Sθ2N(RlO) 2 , R 11 SO2NR 0- and C 1 -C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R^ a and R5b are combined to form - (CH2)s - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0)m, -NC(O)-, and -N(COR lO)- ; or R5a or R5b are combined with R 14 to form a ring such that X-Y is f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R J lS(0) m -. Rl0C(O)NRl0., CN, N02, R l°2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0) m -_ RlOC(0)NH-, CN, H2N-C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO)2, or RH0C(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, RlOC(0)NRl -, CN, N02, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, Rl O-, Rl lS(0) m -, R10C(O)NR 10-, CN, (RlO)2N-C(NRl )., RIOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl 1OC(O)NR10- ; RlO is independently selected from hydrogen, -C6 alkyl and aryl; R 1 1 is independently selected from Cl -C alkyl and aryl; Rl2 is independently selected from hydrogen and C1 -C6 alkyl; Rl4 is independently selected from hydrogen,Cl -C6 alkyl and benzyl; Rl5 is independently selected from hydrogen and -C6 alkyl; Al and A are independently selected from: a bond, -CH=CH-, -CΞC-, O, -N(R lO)-, -C(O)-, -C(O)NRl -, -NRlOC(O)-, -S(0) N(RlO)-, -N(RlO)S(0)2- or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal 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 Al is S(0) and V is not hydrogen if A 1 is a bond, n is 0 and A is S(0)m or a bond; W is a heterocycle; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 4 or 5; and t is 3, 4 or 5; or the pharmaceutically acceptable salts thereof. In a second embodiment of this invention the prodrugs of compounds of formula I are illustrated by the formula II: II wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0) m -, R10C(0)NR10-, CN, N02, (Rl )2N-C(NRlO)-, Rl C(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0)m-, Rl°C(O)NRl ., CN, (R1 ) 2 N-C(NR10)-, RlOC(O)-, R 10 OC(O N3, -N(RlO) 2 , or Rl lθC(O)NRl - ; R2a and R2b 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 C1-C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, R lS(0)m-. R1°C(0)NR10-, CN, (Rl ) 2 N-C(NR O)-, RlOc(O)-, R lOθC(O)-, N3, -N(RlO)2, R lOC(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 R2a and R2b are combined to form - (CH2)s - ; R4 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 C1 -C2O alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, Rl°0-, Rl lS(0)m-, R1°C(0)NR 10-, CN, (RlO)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO)2, R1 10C(0)NR10- and -C20 alkyl, and d) C1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl; or R3 and R4 are combined to form - (CH2)s - . R5a and R5b 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 C1-C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocycle group, wherein the substituent is selected from F, Cl, Br, N(Rl0)2, Nθ2, Rl°0-, Rl lS(0) m -, R10C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, R lOθC(O)-, N3, -N(RlO) 2 , R! 1OC(O)NR10- , -SO2N(Rl ) , R lS02NRlO-and C1-C2O alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R5a and R5b are combined to form - (CH2)s - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0)m . -NC(O)-, and -N(COR l )- ; or R5a or R5b are combined with R 14 to form a ring such that R6 i is a) substituted or unsubstituted C1-C8 alkyl, wherein the substituent on the alkyl is selected from: D aryl, 4) -OR 10, or X-Y is R 7b b) \ f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, RlOC(0)NRlO-, CN, Nθ2, Rl°2N-C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl l S(0) m -, Rl C(0)NH-, CN, H2N-C(NH)-, RlOC(O)-, R lOθC(O)-, N3, -N(R l0)2, or R l lθC(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R l lS(0) m -, R l0C(O)NRl0-, CN, N02, (Rl°)2N- C(N lO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C l -Cβ alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl l S(0) m -, Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO) 2 , or R l lθC(O)NRl0. ; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl2 is independently selected from' hydrogen and C1 -C6 alkyl; R 3 is independently selected from Cl-C6 alkyl; Rl4 is independently selected from hydrogen,Ci-C6 alkyl and benzyl; Rl5 is independently selected from hydrogen and C1 -C6 alkyl; A and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NR l0-, O, -N(RlO)-, -NRl C(O)-, -S(O)2N(Rl0)-, -N(Rl )S(0)2- or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal 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 Al is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A is S(0)m or a bond; W is a heterocycle; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; p is 0, 1 , 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 4 or 5; and t is 3, 4 or 5; or the pharmaceutically acceptable salts thereof. In a third embodiment of this invention, the inhibitors of famesyl transferase are illustrated by the formula IE: wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0) m -, R!0C(O)NR10-, CN, N02, (RlO)2N-C(NRlO)-, RlOC(O)-, R10OC(O , N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, R 1 lS(0)m-, R 10 C(O)NRl0-, CN, (R1 ) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-; R2a and R2b 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 -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R 10 C(O)NRl0_. CN, (RlO)2N-C(NRlO)., RIO O)-, R lOθC(O)-, N3, -N(Rl )2, RH OC(O)NR10- and C1 -C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, Rl°0-, Rl lS(0) m -, R10C(O)NR10-, CN, (RlO)2N-C(NR 10 )-, Rl°C(0)-, RlOθC(O)-, N3, -N(RlO)2, RUOC(0)NR10- and C1-C2O alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R3 and R4 are combined to form - (CH2)s - . X-Y is f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C 1 -C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; 8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N02, R 10 2N-C(NR O)-, RlOC(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO)2, or Rl l0C(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0)m-, Rl°C(O)NRl0., CN, NO2, (Rl°)2N- C(NRl )., RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, R lOc(O)-, RlOθC(O)-, N3, -N(R lO)2, or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl2 is independently selected from hydrogen and C1 -C6 alkyl; Rl4 is independently selected from hydrogen,Cι-Q5 alkyl and benzyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NR l0-, O, -N(R10)-, -NRlOC(O)-, -S(0)2N(Rl )-, -N(R l )S(0)2- or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) Cl -C20 alkyl wherein from 0 to 4 non-terminal 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 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle; Z is independently H2 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 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; and s is 4 or 5; or the pharmaceutically acceptable salts thereof. In a fourth embodiment of this invention the prodrugs of compounds of formula III are illustrated by the formula IV: V - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - IV wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOo-, Rl lS(0)m-_ R 10 C(O)NRl0-, CN, Nθ2, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl0)2, or Rl lOC(O)NRl0-, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, R 1 !S(0) m -, Rl0c(O)NRl0-, CN, (R10) 2 N-C(NR 10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or R HOC(O)NR10- ; R2a and R2b 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 C1 -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, RlOO-, Rl lS(0)πr. R 10 C(O)NRl0-, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , Rl lθC(O)NRl0- and C1 -C20 alkyl, and d) C1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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-C2O alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, Rl°0-, Rl lS(0)m-, R1°C(0)NR 10., CN, (Rl ) N-C(NRlO)-, RlOC(O)-, R lOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and C1-C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R3 and R4 are combined to form - (CH2)s - ; X-Y is (0) m d) f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R lOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N02, R1°2N-C(NR10)-, Rl C(O)-, Rl θC(O)-, N3, -N(Rl ) 2 , or Rl lθC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, 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 Rl lθC(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0)m-, R 10C(O)NR1 -, CN, Nθ2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(R l ) 2 , or R HOC(0)NR10- ; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl is independently selected from hydrogen and -C6 alkyl; Rl4 is independently selected from hydrogen,Cl -C6 alkyl and benzyl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(0)NR 1 -, O, -N(R 10)-, -NR 10C(O)-, -S(0)2N(R l , -N(RlO)S(0)2- or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal 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 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle; Z is independently H2 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 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; and s is 4 or 5; or the pharmaceutically acceptable salts thereof. In a more preferred embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the formula I: wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, RlOO-, -N(RlO)2 or alkenyl, c) C1 -C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, RlOO-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted C l -C 10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or 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(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, Rl lOC(O)NRl0. and C1-C20 alkyl, and c) C1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; and R2b is selected from hydrogen and C1-C6 alkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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 Cj-Cio alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0) m -, RlOC(0)NRlO-, CN, (Rl ) 2 N-C(NRlO)., RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , Rl lOC(O)NRl0- and C1-C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl; R5a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from methionine and glutamine, 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 C 1 -C 10 alkyl, C2-C 10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R1 C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , Rl lOC(O)NRl0-, -Sθ2N(RlO) 2 , Rl ISO2NRIO- and -C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl; R5b i selected from: a) hydrogen, and b) Cι-C3 alkyl; or R5a or R5b are combined with R 14 to form a ring such that X-Y is θ) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl -C6 perfluoroalkyl, F, Cl, RlOO-, R10C(O)NR10-, CN, N02, (RlO)2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, -N(Rl )2, or Rl lθC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOo-, Rl0c(O)NRl0., (RlO) 2 N-C(NRlO)-, RlOC(O)-, Rl θC(O)-, -N(RlO)2, or Rl lθC(O)NRl - ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R 1 C(O)NR10-, CN, NO2, (Rl0)2N-C(NRl0)-, Rl0c(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1 -C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, R OO-, Rl lS(0)m-, RlOC(0)NRl -, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0- ; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from Cl -Cβ alkyl and aryl; Rl2 is independently selected from hydrogen and -C6 alkyl; Rl4 is independently selected from hydrogen and -C6 alkyl; Rl5 is independently selected from hydrogen and C1-C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(Rl )-, -NRlOC(O)-, -S(O)2N(Rl0)-, -N(Rl )S(O)2- or S(0) m ; V is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 2; s is 4 or 5; and t is 3, 4 or 5; or the pharmaceutically acceptable salts thereof. In a second more preferred embodiment of this invention, the prodrugs of the preferred compounds of formula I are illustrated by the formula II: (R I 8 )r ψ Z R 2a R 2b Z R 5a R 5b V - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - W - (CR 11 2 ~')P p p12 * \ Q R14 II R 3 R 4 wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, R 10θ-, -N(R 10)2 or alkenyl, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, RlOO-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl- o alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0) m -, R !0C(O)NR 10-, CN, (Rl ) 2 N-C(NRlO)-, RlOC(O)-, R lOθC(O)-, N3, -N(Rl )2, Rl lθC(O)NRl0- and C1-C20 alkyl, and c) C l -Cβ alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; and R2b is selected from hydrogen and Cl-Cβ alkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, Nθ2, Rl°0-, Rl lS(0)m-, R1°C(0)NR10-, CN, (Rl0)2N-C(NRl0)-, RlOC(O)-, RlOoC(O)-, N3, -N(R lO)2, Rl lOC(O)NRl0- and -C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R5a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from methionine and glutamine, 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-. R1°C(0)NR10-, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, Rl°OC(0)-, N3, -N(Rl )2, RH OC(O)NR10-, -SO2N(Rl0)2, Rl ISO2NRIO- and C1-C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R5a is selected from: a) hydrogen, and b) Cl-C3 alkyl; or R5a or R5b are combined with R 14 to form a ring such that a) substituted or unsubstituted Cl-CR alkyl, wherein the substituent on the alkyl is selected from: D aryl, 4) -OR 10, or b) R 12 O • TXor X-Y is )7a c) y ^ * b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C l -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C 1 -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C 1 -C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, 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 l O-, R1 C(O)NR10-, CN, N02, (R1°)2N-C(NR10)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, and c) Cl-Cfe alkyl substituted by C1 -C6 perfluoroalkyl, Rl O-, Rl0C(O)NRl0-, (R 10) 2 N-C(NR10)-, 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, Rl O-, Rl lS(0) m -, R! C(O)NR 1 -, CN, Nθ2, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, R lS(0)m-, Rl0C(O)NRl0-, CN, R IOC(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lθC(O)NRl0- ; R 1 is independently selected from hydrogen, C l -C6 alkyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and Cl -Cβ alkyl; Rl3 is 1 ,1-dimethylethyl; Rl4 is independently selected from hydrogen and C1 -C6 alkyl; Rl^ is independently selected from hydrogen and Cl -C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)., -NRlOC(O)-, -S(0)2N(RlO)-, -N(Rl )S(0)2- or S(0) m ; V is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C 1 -C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C2O alkenyl; provided that V is not hydrogen if Al is S(0) m and V is not hydrogen if A 1 is a bond, n is 0 and A is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 2; s is 4 or 5; and t is 3, 4 or 5; or the pharmaceutically acceptable salts thereof. In a third more preferred embodiment of this invention, the inhibitors of famesyl transferase are illustrated by the formula HI: wh , erein: R 1 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, Rl O-, -N(R l )2 or alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, Rl O-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl-ClO alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)nr, R 1°C(0)NR 10-, CN, (R 10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and C1-C2O alkyl, and c) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; and R2b is selected from hydrogen and C1 -C6 alkyl; or R a and R2b are combined to form - (CH2)s - ; R3 and R4 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R1°C(0)NR10-, CN, (R 10) 2 N-C(NR1 )-, RlOc(O)-, R IOOC(O)-, N3, -N(RlO)2, Rl lθC(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; X-Y is 7b b) \ X H d > y^ , or H e) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci -Cό perfluoroalkyl, F, Cl, Rl O-, R1 C(0)NR _, CN, N02, (R1°)2N-C(NR10)-, R10C(O)-, R IOOC(O)-, -N(Rl )2, or Rl lθC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, R10C(O)NR1°-, (R10)2N-C(NR10)-, Rl c(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-, Rl lS(0) m -, R!0C(O)NR1 -, CN, N02, (R10) 2 N-C(NR10)-, RlOc(O)-, RlOθC(O)-, -N(Rl )2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl !S(0)m-, Rl0c(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, R lOc(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl 1OC(O)NR10- ; RlO is independently selected from hydrogen, C1 -C6 alkyl and aryl; R l 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and Cl -C6 alkyl; R l4 is independently selected from hydrogen and C1 -C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)., -NRlOC(O)-, -S(0)2N(Rl )., -N(Rl )S(0)2- or S(0) m ; V is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 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 or 2; r is 0 to 2; and s is 4 or 5; or the pharmaceutically acceptable salts thereof. In a fourth more preferred embodiment of this invention, the prodmgs of the preferred compounds of formula in are illustrated by the formula IV: IV wherein: R1 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, RlOO-, -N(R l0)2 or alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, RlOO-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl-ClO alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, RlOO-, Rl lS(0)m-. R1°C(0)NR10-, CN, (R10) 2 N-C(NR10)., RlOc(O)-, R lOθC(O)-, N3, -N(RlO)2, RHOC(O)NR10- and C1 -C2O alkyl, and c) C 1 -Cβ alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; and R2b is selected from hydrogen and C1 -C6 alkyl; or R2a and R2b are combined to form - (CH2)s - . R3 and R4 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, Nθ2, Rl°0-, Rl lS(0)πr, R1°C(0)NR10-, CN, (R10) N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , Rl lOC(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; X-Y is e) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C l -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, 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)NR10-, CN, Nθ2, (R10) 2 N-C(NR10)., RlOc(O)-, RlOθC(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0_, and c) C 1 -C6 alkyl substituted by C 1 -C6 perfluoroalkyl, RIOQ., Rl0c(O)NRl0-, (R10)2N-C(NR10)-, Rl°C(0)-, Rl θC(O)-, -N(Rl ) 2 , or Rl 10C(0)NR 10-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)m-, R 1°C(0)NR 10-, CN, N02, (Rl0) 2 N-C(NRl0)-, Rl0c(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl OC(O)NRl0-, and c) C l -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, Rl l S(0) m -. R10C(O)NR -, CN, (Rl ) 2 N-C(NRl )-, RlOc(O)-, Rl°OC(0)-, -N(Rl ) 2 , or Rl 10C(0)NR10- ; Rl is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and C1-C6 alkyl; Rl4 is independently selected from hydrogen and C1-C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, -NRl c(O)-, -S(0)2N(Rl )-, -N(RlO)S(0)2- or S(0) m ; V is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 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 or 2; r is 0 to 2; and s is 4 or 5; or the pharmaceutically acceptable salts thereof. The preferred compounds of this invention are as follows: N-[2(S)-(l-(Phenylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-4-ylacety l)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(Phenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- 5 methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-5-y lacety l)-amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester i o N-[2(S)-( 1 -(4-Nitropheny Imethy 1)- 1 H-imidazol-4-y lacety l)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[(2S)-(l-(4-Nitrophenylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester 15 N-[2(S)-(l-(4-Nitrophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthy lmethyl-glycy 1-methionine N-[2(S)-(l-(4-Nitrophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- 2 o methy lpentyl]-N- 1 -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylacety l)amino-3(S)- methylpentyl]-N- 1 -naphthy lmethyl-glycy 1-methionine 25 N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N- [2(S)-( 1 -( 1 -Naphthylmethyl)- 1 H-imidazol-5-ylacety l)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine 30 N-[2(S)-( 1 -( 1 -Naphthylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(1 -Famesyl- 1 H-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-Fa esyl-lH-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- 5 N-1-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-Geranyl-lH-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- N- 1 -naphthylmethyl-glycyl-methionine i o N-[2(S)-( 1 -Geranyl- 1 H-imidazol-5-ylacetyl)amino-3(S)-methylpentyl] - N-1-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine 15 N-[2(S)-( 1 -(4-Pyridylmethyl)- 1 H-imidazol-4-ylacety l)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-5-ylacetyl)amino-(3S)- o methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester 5 N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthy Imethy 1-glycyl-methionine methyl ester 0 N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l-naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Ouinolinylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- 5 methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Quinolinylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester x o N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-y lacetyl)amino-3(S)- methylpenty 1]-N- 1 -phenylmethyl-glycyl-methionine N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -phenylmethyl-glycyl-methionine methyl ester 15 N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylethy l)amino-3(S)- methylpentyl]-N-l -naphthy lmethyl-glycy 1-methionine N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-y lethy l)amino-3(S)- 20 methy lpentyl]-N-l -naphthy lmethyl-glycyl-methionine methyl ester 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester 25 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine sulfone 2(S)-[N-2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylethyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine methyl ester 30 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylethyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine N-[2(S)-(l-Methyl-lH-imidazol-4-ylacetyl)-amino-3(S)-methylpentyl]- N-(l -naphthy Imethy l)-glycyl-methionine methyl ester N-[2(S)-( 1 -Methyl- lH-imidazol-4-ylacetyl)-amino -3(S)-methylpentyl]- N-( 1 -naphthy Imethy l)-glycyl-methionine N-[2(S)-N-(2-Naphthylmethyl)- 1 H-imidazol-5-ylacetyl]amino-(3S)- methylpentyl]-N-(cyclopropylmethyl)-glycylmethionine methyl ester N-[(2S)-N-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]amino-(3S)- methylpentyl]-N-(cyclopropylmethyl)-glycylmethionine N-[2(S)-[(5(R,S)-Methylpyroglutamyl)amino]-3(S)-methylpentyl]-N-(l - naphthylmethyl)-glycylmethionine methyl ester N-[2(S)-[(5(R,S)-Methylpyroglutamyl)amino]-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycylmethionine N-[2(S)-((N-Methylpyroglutamyl)amino)-3(S)-methylpentyl]-N-( 1 - naphthy lmethyl)-glycyl-methionine N-[2(S)-((N-Methylpyroglutamyl)-amino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N-Formylprolylamino)-3(S)-methylpentyl]-N-(l - naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N-Formylprolylamino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine N-[2(S)-(N'-(4-Nitrobenzyl)pyroglutamyl)-amino)-3(S)-methylpentyl]- N-(l-naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N'-(4-Nitrobenzyl)pyroglutamyl)-amino)-3(S)-methylpentyl]- N-( 1 -naphthylmethyl)-glycyl-methionine N-[2(S)-((N'-Benzylpyroglutamyl)amino)-3(S)-methylpentyl]-N-(l- 5 naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N'-Benzylpyroglutamyl)amino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine i o N-[2(S)- 1 -(4-Fluorophenylmethyl)- 1 H-imidazol-5-ylacety l)amino-3(S)- methylpentyl]-N-l -naphthy Imethy 1-glycyl-methionine methyl ester N-[2(S)- 1 -(4-Fluoropheny Imethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthy Imethy 1-glycyl-methionine 15 N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine isopropyl ester N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- o methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine sulfone methyl ester N-[2(S)-([ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthy lmethyl)glycyl-methionine sulfone 25 N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-(3-acetylamino)alanine methyl ester o N-[2(S)-([ 1 -(4-cyanobenzyl)-l H-imidazol-5-yl]acetylamino)-3(S)- methylpenty l]-N-( 1 -naphthylmethyl)glycyl-(3-acetylamino)alanine N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-2(RS) amino-3-(2 thienyl)propionic acid methyl ester 5 N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-2(RS)-amino-3-(2 thienyl)propionic acid N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- l o methy lpentyl]-N-( 1 -naphthylmethyl)glycyl-2(S) amino-4-sulfamyl- butanoic acid methyl ester N-[2(S)-([l -(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpenty l]-N-( 1 -naphthy Imethy l)glycy 1-2(S) amino-4-sulfamyl- 15 butanoic acid N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-N-methyl methionine methyl ester 0 N-[2(S)-([l -(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-N-methyl methionine N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- 5 methylpentyl]-N-(l -naphthylmethyl )glycyl-homoserine lactone N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycy 1-homoserine 0 N-[2(S)-([ l-(4-cyanobenzyl)-lH-imidazoi-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-proline methyl ester N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthy lmethyl)glycyl-proline N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l -naphthylmethyl )glycyl-D-proline methyl ester N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpenty l]-N-( 1 -naphthylmethyl)glycy 1-D-proline N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-L- pipecolinic acid N-[2(S)-([ 1 -(4-carbomethoxybenzyl)-l H-imidazol-5-yl]acetylamino)- 3(S)-methylpenty l]-N-( 1 -naphthylmethyl)glycyl-methionine methyl ester N-[2(S)-([ 1 -(4-carbomethoxybenzyl)-l H-imidazol-5-yl]acetylamino)- 3(S)-methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine 1 -(2-naphthylmethyl)- 1 H-imidazol-5-ylacetyl-isoleucinyl- phenylalaninyl-methionine methyl ester 1 -(2-naphthy Imethy 1)- 1 H-imidazol-5-y lacetyl-isoleucinyl- phenylalaninyl-methionine or the pharmaceutically acceptable salts thereof. Representative compounds of the invention are: N-[2(S)-( l-(4-Nitropheny Imethy 1)-1 H-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l -(4-Nitrophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine isopropyl ester N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l -(4-Methoxyphenyl-methyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(2-Naphthylphenyl-methyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l -naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S methylpentyl]-N-l -naphthy lmethyl-glycy 1-methionine sulfone methyl ester N-[2(S)-(l -(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthylmethyl-glycyl-methionine sulfone N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-2-(acetylamino)alanine methyl ester N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-2-(acetylamino)alanine methyl ester N-[2(S)-(1 -(4-Cyanophenylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methy lpenty 1]-N- 1 -naphthylmethyl-glycyl-N-methyl-methionine N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthylmethyl-glycyl-N-methyl-methionine methyl ester or the pharmaceutically acceptable salts 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. 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 heterocyclic 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 stmcture. 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, moφholinyl, naphthy ridinyl, oxadiazolyl, 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, thiamoφholinyl, thiamoφholinyl 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, NH2, N(Cl -C6 alkyl)2, CF3, N02, (C1 -C6 alkyOO-, -OH, (C1-C6 alkyl)S(0) m -, (C1-C6 alkyl)C(0)NH-, H2N-C(NH)-, (C1-C6 alkyl)C(O)-, (C1-C6 alkyl)OC(O)-, N3, CN, (C1-C6 alkyl)OC(0)NH- and C1 -C2O alkyl. The following stmcture: 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: When R2 and R2b and R3 and R4 are combined to form - (CH2)s -. cyclic moieties are formed. Examples of such cyclic moieties include, but are not limited to: When R 5a and R5b are combined to foim - (CH2)s -, cyclic moieties as described hereinabove for R2 and R2b and R3 and R4 are formed. In addition, such cyclic moieties may optionally include a heteroatom(s). Examples of such heteroatom-containing cyclic moieties include, but are not limited to: Preferably, Rl is selected from: hydrogen, and C1-C6 alkyl. Preferably, R2a and R2b are independently selected from: a side chain of a naturally occurring amino acid and C1-C6 alkyl unsubstituted or substituted with an aryl group. Preferably, R3 and R4 are independently selected from: a side chain of a naturally occurring amino acid and C1-C6 alkyl unsubstituted or substituted with a group selected from aryl, heterocycle and C3-C10 cycloalkyl. Preferably, R^ and R^b are independently selected from: a side chain of a naturally occurring amino acid, methionine sulfoxide, methionine sulfone and unsubstituted or substituted C1-C6 alkyl . Preferably, X-Y is selected from: R 7b \ .N and . * • - i - Preferably, R?b C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted aryl group. Preferably, R8 is selected from: hydrogen, perfluoroalkyl, F, Cl, Br, R lOO-, Rl lS(0) m -, CN, Nθ2, R 10 C(O)-, RlOθC(O)-, -N(Rl0) 2 , Rl 1OC(O)NR10- and -C6 alkyl. Preferably, R9 is hydrogen. Preferably, Rl is selected from H, -C6 alkyl and benzyl. Preferably, Al and A2 are a bond. Preferably, V is selected from hydrogen, heterocycle and aryl. 5 Preferably, n, p and r are independently 0, 1 , or 2. Preferably t is 3. 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 l o 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, 15 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 20 variable (e.g., R 10, Z, n, etc.) at a particular location in a molecule be independent of its definitions elsewhere in that molecule. Thus, -N(R10) 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 25 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. The pharmaceutically acceptable salts of the compounds of this invention can be synthesized from the compounds of this 30 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 their constituent amino acids by conventional peptide synthesis techniques, and the additional methods 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. The teachings of these works are hereby incoφorated by reference. Abbreviations used in the description of the chemistry and in the Examples that follow are: THF Tetrahydrofuran. 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 1 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. REACTION SCHEME A Reaction A. Coupling of residues to form an amide bond HCI or ? H 9 TFA N . H 2 N ^OR O R B REACTION SCHEME B Reaction B. Preparation of reduced peptide subunits by reductive alkylation NaCNBH 3 RHACTION SCHEME C Reaction C. Alkylation/reductive alkylation of reduced peptide subunits R C CH, NaCNBH 3 R b REACTION SCHEME D Reaction D. Coupling of residues to form an amide bond REACTION SCHEME E Reaction E. Preparation of reduced dipeptides from peptides where RA and RB are R2a, R2b, R3, R4, R5a or I#b as previously defined; XL is a leaving group, e.g., Br, I- or MsO-; and R s defined such that R7b is generated by the reductive alkylation process. Reaction Schemes A-E illustrate bond-forming and peptide modifying reactions incoφorating acyclic peptide units. It is well understood that such reactions are equally useful when the - NHC(RA) - moiety of the reagents and compounds illustrated is replaced with the following moiety: Certain compounds of this invention wherein X- Y is an ethenylene or ethylene unit are prepared by employing the reaction sequences shown in Reaction Schemes F and G. Reaction Scheme F outlines the preparation of the alkene isosteres utilizing standard manipulations such as Weinreb amide formation, Grignard reaction, acetylation, ozonolysis, Wittig reaction, ester hydrolysis, peptide coupling reaction, mesylation, cleavage of peptide protecting groups, reductive alkylation, etc., as may be known in the literature or exemplified in the Experimental Procedure. The key reactions are: stereoselective reduction of the Boc-amino-enone to the corresponding syn amino-alcohol (Scheme F, Step B, Part 1), and stereospecific boron triflouride or zinc chloride activated organo- magnesio, organo-lithio, or organo-zinc copper(l) cyanide SN ' displacement reaction (Scheme F, Step G). Through the use of optically pure N-Boc amino acids as starting material and these two key reactions, the stereo-chemistry of the final products is well defined. In Step H of Scheme F, R* is incoφorated using coupling reaction A and RlCOOH; the alkylation reaction C using R*CHO and a reducing agent; or alkylation reaction C using R*CH2XL. The alkane analogs are prepared in a similar manner by including an additional catalytic hydrogenation step as outlined in Reaction Scheme G. REACTION SCHEME F Step A 1. NaBH 4 OAc BocNH, 2. Ac 2 0, Py R 2a Step B 1. 0 3 , Me 2 S OAc 2. Ph 3 P=CHC0 2 Me BocNH. C0 2 Me Step C R 2a REACTION SCHEME F (CONT'D) R 3 MgCuCNCIBF 3 Step G 3 REACTION SCHEME F (CONT'D) NaOH or 10 1. HCI Alternate Step H O II 2. R x COH 15 EDC, HOBT W" NaOH 30 REACπON SCHEME G I.NaBH, OAc 1.0 3 , Me 2 S BocNH. 2. Ac 2 0,py 2. Ph 3 P=CHC0 2 Me )2a BocNH REACTION SCHEME G (CONT'D) BocNH 1. R 3 MgCuCNCI « BF 3 2. H 2 , 5% Pd/C Step K 10 15 1. HCI 2. NaCNBH 3 , R x CHO REACΗON SCHEME G (CONT'D) or o 1. HCI 2. R x COH EDC, HOBT NaOH The oxa isostere compounds of this invention are prepared according to the route outlined in Scheme H. An aminoalcohol H-l is acylated with alpha-chloroacetyl chloride in the presence of trialkylamines to yield amide H-2. Subsequent reaction of H- 2 with a deprotonation reagent (e.g., sodium hydride or potassium t-butoxide) in an ethereal solvent such as THF provides moφholinone H-3. The N-Boc derivative H-4 is then obtained by the treatment of H_θ with BOC anhydride and DMAP (4- dimethylaminopyridine) in methylene chloride. Alkylation of H-4 with R3χL. where XL is a leaving group such as Br, I- or Cl- in THF/DME (1,2-dimethoxyethane) in the presence of a suitable base, preferably NaHMDS [sodium bis(trimethylsilyl)amide], affords H-5. which is retreated with NaHMDS followed by either protonation or the addition of an alkyl halide R4χ to give H-6a or H-6b. respectively. Alternatively, H-6a can be prepared from H-4 via an aldol condensation approach. Namely, deprotonation of H-4 with NaHMDS followed by the addition of a carbonyl compound RyRzCO gives the adduct H-7 (wherein Ry and R z are selected such that R3 is eventually provided. Dehydration of H-7 can be effected by mesylation and subsequent elimination catalyzed by DBU (1 ,8- diazabicyclo[5.4.0]undec-7-ene) or the direct treatment of H-7 with phosphorus oxychloride in pyridine to give olefin H-8. Then, catalytic hydrogenation of H-8 yields H-6a. Direct hydrolysis of H-6 with lithium hydrogen peroxide in aqueous THF will produce acid H^ 9b. Sometimes, it is more efficient to carry out this conversion via a 2-step sequence, namely, hydrolysis of H-6 in hydrochloric acid to afford H-9a. which is then derivatized with BOC-ON or BOC anhydride to give H-9b. The peptide coupling of acid H-9b with either an alpha-aminolactone (e.g., homoserine lactone, etc.) or the ester of an amino acid is carried out under the conditions exemplified in the previously described references to yield derivative H-10. Treatment of H-10 with gaseous hydrogen chloride gives H-l l. which undergoes reductive alkylation in the presence of an aldehyde RxCHO (H-12) and a reducing agent (e.g., sodium cyanoboro¬ hydride); or acylation in the presence of RxCOOH (H-l 3) and a peptide coupling reagent affording the products H-l 4a and b. Hydrolysis of compounds H-14 to the corresponding hydroxy acids and acids, respectively, is accomplished by standard methods such as treatment with NaOH in alcoholic or aqueous milieux followed by careful acidifcation with dilute HC1. SCHEME H Jbl Ϊ±Z J±2 SCHEME H (CONTD) LiOOH; oraq. HCI, then BOC 2 0 ϊ±a. a, R w = H b, R w = BOC 10 H-10 ±A1 25 30 SCHEME H (CONT'D) A = The thia, oxothia and dioxothia isostere compounds of this invention are prepared in accordance to the route depicted in Scheme I. Aminoalcohol . is derivatized with BOC2O to give 1-15. Mesylation of 1-15 followed by reaction with methyl alpha- mercaptoacetate in the presence of cesium carbonate gives sulfide Ii 16. Removal of the BOC group in 1-16 with TFA followed by neutralization with di-isopropylethylamine leads to lactam 1-17. N- BOC derivative 1-18 is obtained via the reaction of 1-17 with BOC anhydride in THF catalyzed by DMAP. Sequential alkylation of 1-18 with the alkyl halides R3χ and R4χ in THF/DME using NaHDMS as the deprotonation reagent produces 1-19. Hydrolysis of 1-19 in hydro-chloride to yield I-20a. which is derivatized with Boc anhydride to yield I-20b. The coupling of I-20b with an alpha- aminolactone (e.g., homoserine lactone, etc.) or the ester of an amino acid is carried out under conventional conditions as exemplified in the previously described references to afford 1-21. Sulfide 1-21 is readily oxidized to sulfone 1-22 by the use of MCPB A (m- chloroperoxybenzoic acid). The N-BOC group of either 1-21 or 1-22 is readily removed by treatment with gaseous hydrogen chloride. The resultant amine hydrochloride 1-23 undergoes reductive alkylation in the presence of an aldehyde RxCHO (1-12) and a reducing agent (e.g., sodium cyanoborohydride); or acylation in the presence of RxCOOH (1-13) and a peptide coupling reagent to afford the products 1-24 and 1-25. SCHEME I SCHEME I (CONT'D) m=0J:2Q MCPBA m=2,L2 * 1-23 NaCNBH 3 _ \_2_1 m = 0 or 2 R 1 COOH EDC, HOBT L25 Reaction Schemes J - M illustrate reactions wherein the non- sulfhydryl-containing moiety at the N-terminus of the compounds of the instant invention is attached to an acyclic peptide unit which may be further elaborated to provide the instant compounds. 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 reactions described in Reaction Schemes A - E. The intermediates whose synthesis are illustrated in Reaction Schemes A and C can be reductively alkylated with a variety of aldehydes, such as V, as shown in Reaction Scheme J. 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, from the appropriate amino acid (Reaction Scheme J). 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 VI can be deprotected to give the final compounds VII with trifluoroacetic acid in methylene chloride. The final product VII is isolated in the salt form, for example, as a trifluoroacetate, hydrochloride or acetate salt, among others. The product diamine VII can further be selectively protected to obtain VIII, which can subsequently be reductively alkylated with a second aldehyde to obtain IX. Removal of the protecting group, and conversion to cyclized products such as the dihydroimidazole XI can be accomplished by literature procedures. Alternatively, the protected dipeptidyl analog intermediate can be reductively alkylated with other aldehydes such as 1 -trityl-4- carboxaldehyde or 1 -trityl-4-imidazolylacetaldehyde, to give products such as XII (Reaction Scheme K). The trityl protecting group can be removed from XII to give XIII, or alternatively, XII can first be treated with an alkyl halide then subsequently deprotected to give the alkylated imidazole XIV. Altematively, the dipeptidyl analog intermediate can be acylated or sulfonylated by standard techniques. The imidazole acetic acid XV can be converted to the acetate XVII by standard procedures, and XVII can be first reacted with an alkyl halide, then treated with refluxing methanol to provide the regiospecifically alkylated imidazole acetic acid ester XVIII. Hydrolysis and reaction with the protected dipeptidyl analog intermediate in the presence of condensing reagents such as l-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC) leads to acylated products such as XIX. Similar procedures as are illustrated in Reaction Schemes J- M may be employed using other peptidyl analog intermediates such as those whose synthesis is illustrated in Reaction Schemes B - 1. REACΗON SCHEME J Et 3 N , CICH 2 CH 2 CI VI VII VIII REACΗON SCHEME J (continued) REACTION SCHEME K REACTION SCHEME L XV XVI XVII XVIII 20 25 30 REACΗON SCHEME M XIX The compounds of this invention inhibit Ras famesyl transferase which catalyzes the first step in the post-translational processing of Ras and the biosynthesis of functional Ras protein. These 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, and myeloid leukemias. The compounds of this invention are also useful for inhibiting 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, the benign proliferative disorder neurofibromatosis, or tumors in which the Ras is activated due to mutation or overexpression of tyrosine kinase oncogenes (e.g., neu, src, abl, lck, and fyn) may be inhibited by the compounds of this invention. Furthermore, arteriosclerosis and diabetic disturbance of blood vessels may be prevented or treated by use of the instant compounds to inhibit proliferation of vascular smooth muscle cells. 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 com starch, and lubricating agents, such as magnesium stearate, are commonly added. For oral administration in capsule form, useful diluents include lactose and dried com 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. 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 famesylate 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. The standard workup referred to in the examples refers to solvent extraction and washing the organic solution with 10% citric acid, 10% sodium bicarbonate and brine as appropriate. Solutions were dried over sodium sulfate and evaporated in vacuo on a rotary evaporator. EXAMPLE 1 Preparation of N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-4-yl- acetyl)amino-3(S)-methylpentyl]-N-l-naphthylmethyl-glycyl-methionine bis trifluoroacetate (13) and N-[2(S)-(1 -(Phenylmethyl)- 1 H-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate (14) Step A: Preparation of 1 H-Imidazole-4-acetic acid methyl ester- hydrochloride (1) Into a solution of lH-imidazole-4-acetic acid hydrochloride (4 g, 24.6 mmol) in methanol (100 ml) was bubbled hydrogen chloride gas until saturated. This solution was allowed to stand for 18 h at room temperature and the solvent evaporated in vacuo to give (1) as a white solid. lH NMR (CDC13, 400 MHz) δ 8.85 (1H, s), 7.45 (1H, s), 3.89 (2H, s) and 3.75 (3H, s) ppm. Step B: Preparation of 1 -(Phenylmethyl)- 1 H-imidazol-4-ylacetic acid methyl ester (2) and 1 -(Phenylmethyl)- lH-imidazol-5- ylacetic acid methyl ester (3) (3:1 mixture) To a solution of sodium hydride (37.3 mg, 1.56 mmol) in dimethylformamide (2 ml) cooled to 0°C (ice bath) was added, via cannula, a solution of 1 (1 15 mg, 0.707 mmol) in dimethylformamide (3 ml). This suspension was allowed to stir at 0°C for 15 min. To this suspension was added benzyl bromide (84 μL, 0.707 mmol) and the mixture was stirred at room temperature for 2h. After this time, the mixture was quenched with sat. aq. sodium bicarbonate (15 ml) and water (20 ml) and extracted with methylene chloride (2 x 50 ml). The combined extracts were washed with brine (20 ml), dried (MgSθ4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography eluting with acetonitrile to give a 3: 1 mixture of 2 and 3. !H NMR (CDC13, 400 MHz) δ 7.53 (0.25H, s), 7.48 (0.75H, s), 7.35 (3H,m), 7.18 (1.5H, d, J=7.4 Hz), 7.06 (0.5H, d, J=7.2 Hz), 7.00 (0.25H, s), 6.87 (0.75H, s), 5.16 (0.5H, s), 5.08 (1.5H, s), 3.72 (1.5H, s), 3.65 (2.25H, s), 3.63 (0.75H, s) and 3.48 (0.5H, s) ppm. Step C: Preparation of 1 -(Phenylmethyl)- lH-imidazol-4-ylacetic acid hydrochloride (4) and 1 -(Phenylmethyl)- lH-imidazol- 5-ylacetic acid hydrochloride (5) (3: 1 mixture) A solution of 2 and 3 (3: 1 mixture, 106 mg) in 1.0 N HCI (3 ml) was heated to 45°C for 4 h. After this time, the solution was evaporated in vacuo to give a 3:1 mixture of 4 and 5. iH NMR (DMSO, 400 MHz) δ 9.26 (0.75H, s), 9.23 (0.25H, s), 7.60 (0.25H, m), 7.58 (0.75H, s), 7.45-7.26 (5H, m), 5.43 (0.5H, s), 5.41 (0.5H, s), 3.77 (1.5H, s), 3.75 (0.5H, s) ppm. Step D: Preparation of N-(2(S)-(t-butoxycarbonylamino)-3(S)- methylpentvPglvcine methyl ester (6) 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 to a small volume and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2 x 50 mL). The combined organic phase was washed with aqueous saturated NaHCθ3 solution, brine, and dried (Na2Sθ4). Filtration and concentration afforded a residue which was purified by flash chromatography (Siθ2, EtOAc:hexane, 1 :3) to give (6). IH NMR (CDC13) δ 4.69 (IH, m), 3.72 (3H, s), 3.48-3.62 (IH, m), 3.42 (2H, ABq), 2.65 (2H, d, J=6 Hz), 1.4-1.6 (2H, m), 1.48 (9H, s), 1.04-1.2 (IH, m), 0.85-0.95 (6H, m) ppm. Step E: Preparation of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyn-N-(l -naphthylmethyl)glvcine methyl ester (7) N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methyl-pentyl]- glycine methyl ester (6, 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 triacetoxy- borohydride (6.65 g, 31.4 mmol). The mixture was stirred at ambient temperature for 16 h, and filtered through glass fiber paper and concentrated. The residue was partitioned between EtOAc and sat. NaHCθ3 (100 ml/25 ml). The aqueous layer was extracted with EtOAc (3x50 ml). The organic layers were combined, dried (Na2Sθ4), filtered, and concentrated to give 5.0 g of crude product which was purified by chromatography (Siθ2, 15-33% ethyl acetate/hexane) to give 7 . IH NMR (CD3OD) 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, ABq), 3.66 (3H, s), 3.40-3.23 (IH, m), 2.90 (IH, dd, J=6 and 15Hz), 2.63 (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 F: Preparation of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyl1-N-( 1 -naphthylmethvDglvcine (8) N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-( 1 - naphthylmethy glycine methyl ester (7, 2.61 g, 6.10 mmol) was dissolved in MeOH (50 ml) and IN NaOH (24.4 ml, 24.4 mmol) was added. The mixture was stirred at ambient temperature for 4 h and concentrated. The resulting residue was dissolved in water (25 ml) and neutralized with IN HCI (24.4 ml). The aqueous layer was washed with EtOAc (3x50 ml). The organic layers were combined, dried with Na2Sθ4, filtered, and concentrated to give the product. H NMR (CD3OD) δ 8.43 (IH, d, J=6Hz), 7.97 (2H, t, J=6 Hz) 7.75-7.48 (4H, m), 4.96 (IH, d, J=12Hz), 4.72 (IH, d, J=12 Hz), 3.80-3.58 (3H, m), 3.49- 3.40 (IH, dd„ J=3 and 12 Hz), 3.03 (IH, dd, J=3 and 12 Hz), 1.42 (9H, s,), 1.37-1.28 (2H, m), 1.80-1.00 (IH, m), 0.94-0.78 (6H, m,) ppm. Step G: Preparation of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycine-methionine methyl ester (9) N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(l - naphthylmethyl)glycine (8, 2.29g, 5.53 mmol), dissolved in DMF (20 mL), was treated with HOBT (0.822 g, 6.08 mmol), EDC (1.17 g, 6.08 mmol), and methionine methyl ester hydrochloride (1.21 g, 6.08 mmol). The pH was adjusted to 7.5 with Et3N (1.7 mL, 12 mmol) and the mixture was stirred at ambient temperature for 24 h. The mixture was concentrated, and the residue was partitioned between EtOAc (50 mL) and saturated NaHCθ3 solution (25 mL). The aqueous layer was extracted with EtOAc (1x30 mL). The organic layers were combined, washed with brine (1x25 mL), dried (Na2Sθ4), filtered, and concentrated to give 3.2 g of crude product which was purified by chromatography (silica gel eluting with 1 :3 to 1 :2 ethyl acetate in hexane) to give pure product. *H NMR (CD3OD) δ 8.33 (IH, d, J=6 Hz), 7.90 (IH, d, J=6 Hz), 7.82 (IH, d, J=6 Hz), 7.61 -7.39 (4H, m), 6.60-6.52 (IH, m), 4.32- 4.06 (2H, m), 3.90-3.69 (IH, m), 3.65 (3H, s), 3.27-3.14 (2H, m), 2.93- 2.70 (2H, m), 2.19-1.78 (6H, m), 1.63-1.30 (13H, m), 1.19-1.05 (lH, m), 0.95-0.81 (6H, m) ppm. Step H: Preparation of N-(2(S)-amino-3(S)-methylpentyl)-N-( 1 - naphthylmethyl)-glycyl-methionine methyl ester hydrochloride (10) N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(l - naphthylmethyl)-glycyl-methionine methyl ester (9, 2.82 g, 5.04 mmol) was dissolved in EtOAc (50 mL) and cooled to -25°C. HCI was bubbled through the mixture until TLC (95:5 CH2θ2:MeOH) indicated complete reaction. Nitrogen was bubbled through the mixture to remove excess HCI and the mixture was then concentrated to give the title compound. l H NMR (CD3OD) δ 8.31 (IH, d, J=6 Hz), 7.96 (2H, d, J=6 Hz), 7.83- 7.71 (IH, m), 7.68-7.49 (3H, m), 4.76-4.55 (4H, m), 3.84-3.75 (2H, m), 3.71 (3H, s), 3.70-3.59 (IH, m), 3.21-3.00 (2H, m), 2.57-2.38 (3H, m), 2.17-2.04 (4H, m), 1.97-1.81 (lH, m), 1.63-1.50 (IH, m), 1.39-1.20 (IH, m), 1.19-1.00 (IH, m), 0.95-0.79 (6H, m) ppm. Step I: Preparation of N-[2(S)-(1 -(Phenylmethyl)- 1 H-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - gylycyl-methionine methyl ester bis trifluoroacetate (11) and N-[2(S)-(1 -(Phenylmethyl)- lH-imidazol-5-ylacetyl)-amino- 3(S)-methylpentyl]-N- 1 -naphthylmethyl - g 1 vc vl-methi onine methyl ester bis trifluoroacetate (12) To a solution of a 1 -(phenylmethyl)- lH-imidazol-4-ylacetic acid hydrochloride (4) and 1 -(phenylmethyl)- lH-imidazol-5-ylacetic acid hydrochloride (5, 3:1 mixture, 1 15 mg, 0.455 mmol), N-[2(S)-amino- 3(S)-methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester bis hydrochloride (10, 244 mg, 0.455 mmol) and 3-hydroxy- 1 ,2,3- benzotriazin-4(3H)-one (HOOBT, 74 mg, 0.46 mmol) in dimethylformamide (5 ml) was added l-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC, 87 mg, 0.455 mmol) and triethylamine (190 μl, 1.36 mmol) and the solution stirred overnight. After this time, sat. aq. sodium bicarbonate (20 ml) and water (25 ml) were added and the mixture was extracted with ethyl acetate (2 X 50 ml). The combined extracts were washed with brine (5 ml) and the solvent evaporated in vacuo. The regioisomers were separated by Prep HPLC using a Nova Prep 5000 Semi preparative HPLC system and a Waters PrepPak cartridge (47 X 300mm, C 18, 15 urn, 100 A) eluting with 5 - 95% acetonitrile/water (0.1% TF A) at 100 ml/min (chromatography method A) to give after lyophilization pure 11 and 12. 11: IH NMR (CD3OD, 400MHz) δ 8.95 (IH, s), 8.27 (IH, m), 7.96 (2H, m), 7.68 (IH, d), 7.60-7.37 (9H, m), 5.38 (2H, s), 5.0-4.8 (IH, m), 4.52 (IH, t, J=10.6 Hz), 4.42 (IH, dd, J=4 and 6.6 Hz), 4.14 (IH, m), 3.92 (IH, d, J=13.3 Hz), 3.83 (IH, d, J=13.3 Hz), 3.70 (IH, s), 3.64 (IH, m), 3.54 (2H, m), 3.22 (IH, dd, J=7 and 8 Hz), 2.37 (IH, m), 2.10 (IH, m), 2.00 (3H, s), 1.98 (IH, m), 1.79 (IH, m), 1.58 (IH, m), 1.42 (IH, m), 1.17 ( 1 H, m) and 0.90 (6H, m) ppm. Anal. Calcd for C37H47N5O4S « 3.0 TFA « 0.15 H20: C, 51.51 ; H, 5.06; N, 6.98. Found: C, 51.52; H, 4.98; N, 7.18. FAB HRMS exact mass calcd for C37H48N5O4S 658.342702 (MH+), found 658.341278. 12: !H NMR (CD3OD, 400 MHz) δ 8.8 (IH, s), 8.26 (IH, m), 7.89 (2H, m), 7.66-7.24 (8H, m), 7.21 (2H, s), 5,36 (2H, m), 4.37 (3H, m), 4.09 (lH.br s), 3.66 (3H, s), 3.56 (3H, m), 3.50-2.90 (3H, m), 2.27 (IH, br s), 2.20 (IH, br s), 1.96 (3H, s), 1.90 (IH, br s), 1.68 (IH, br s), 1.58 (IH, br s), 1.40 (IH, m), 1.18 (IH, m) and 0.89 (6H, m) ppm. Anal. Calcd for C37H47N504S-1.85 TFA-0.10 H2O: C, 56.15; H, 5.68; N, 8.04. Found: C, 56.14; H, 5.62; N, 8.44. FAB HRMS exact mass calcd for C37H48N5O4S 658.342702 (MH+), found 658.343754. Step J: Preparation of N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-4- ylacetyl)amino-3(S)-methylpentyl] -N- 1 -naphthylmethyl - glycyl-methionine bis trifluoroacetate (13) and N-[2(S)-( 1 - (Phenylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthylmethyl-glycyl-methionine bis trifluoroacetate (14) To a solution of N-[2(S)-(1 -(Phenylmethyl)- 1 H-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine methyl ester bis trifluoroacetate (11) and N-[2(S)-(1- (phenylmethyl)- 1 H-imidazol-5-yl)acetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate (12, 2:1 mixture, 50 mg, 0.057 mmol) in methanol ( 5 ml ) was added 1.0N lithium hydroxide (570 μl, 0.547 mmol ). This solution was stirred for 4 h and treated with trifluoroacetic acid (100 μl). This mixture was purified by preparative HPLC using chromatography method A to give the title compounds. 13: !H NMR (CD3OD, 400 MHz) δ 8.83 (IH, s), 8.21 (IH, d, J=9.5 Hz), 7.88 (2H, m), 7.54 (IH, d, J=6.9 Hz), 7.5 - 7.3 (9H, m), 5.32 (2H, s), 4.56 (IH, br d, J = 10 Hz), 4.36 (2H, m), 4.09 (IH, m), 3.55 (4H, m), 3.17 (IH, br d, J = 10 Hz), 2.98 (IH, t, J = 10Hz), 2.29 (IH, m), 2.18 (IH, m), 1.96 (IH, m), 1.95 (3H, s), 1.67 (IH, m), 1.56 (IH, m), 1.37 (IH, m), 1.11 (IH, m) and 0.88 (6H, m) ppm. Anal. Calcd for C36H45N5θ4S«2.15 TFA: C, 54.45; H, 5.35; N, 7.88. Found: C, 54.42; H, 5.30; N, 7.97. FAB HRMS exact mass calcd for C36H46N5O4S 644.327052 (MH+), found 644.326691. 14: Ϊ H NMR (CD3OD, 400 MHz) δ 8.80 (IH, s), 8.29 (IH, m), 7.92 (2H, m), 7.61 (IH, br), 7.32-7.53 (7H, m), 7.21 (2H, br s), 5.37 (2H, s), 4.37 (2H, m), 4.08 (IH, m), 3.57 (4H, br m), 3.05 (2H, m), 2.29 (2H, m), 2.20 (IH, m), 1.96 (3H, s), 1.70 (IH, m), 1.62 (IH, m), 1.57 (IH, m), 1.39 (IH, m), 1.13 (IH, m) and 0.88 (6H, m) ppm. FAB HRMS exact mass calcd for C36H46N5O4S 644.327052 (MH+), found 644.327917. EXAMPLE 2 Preparation of N-[2(S)-(l-(4-Nitrophenylmethyl)-lH-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate (21) and N-[2(S)-(1 -(4- Nitrophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- N-1-naphthylmethyl-glvcyl-methionine bis trifluoroacetate (22). Step A: Preparation of l-(4-Nitrophenylmethyl)-lH-imidazol-4- ylacetic acid methyl ester (15) and 1 -(4-Nitrophenylmethyl)- lH-imidazol-5-ylacetic acid methyl ester (16) (3:1 mixture) To a solution of sodium hydride (60% in mineral oil, 99 mg, 2.5 mmol) in dimethylformamide (2 ml) cooled to 0°C was added, via cannula, a solution of lH-imidazole-4-acetic acid methyl ester hydrochloride (1, 200 mg, 1.13 mmol) in dimethylformamide (3 ml). This suspension was allowed to stir at 0°C for 15 min. To this suspension was added 4-nitrobenzyl bromide (244 mg, 1.13 mmol) and stirred at room temperature for 2 h. After this time, the mixture was quenched with sat. aq. sodium bicarbonate (15 ml) and water (20 ml) and extracted with methylene chloride (2 x 50 ml). The combined organic extracts were washed with brine (20 ml), dried (MgS04), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography using acetonitrile as eluent to give the title compounds as a yellow oil. Ϊ H NMR (CDC13, 400 MHz) δ 8.20 (2H, d, J=8.5 Hz), 7.49 (IH, s), 7.27 (2H, d, J=8.5 Hz), 7.03 (0.25H, s), 6.87 (0.75H, s), 5.28 (0.5H, s), 5.1 (1.5H, s), 3.70 (2.25H, s), 3.65 (1.5H, s), 3.61 (0.75H, s) and 3.44 (0.5H, s) ppm. Step B: Preparation of 1 -(4-Nitropheny Imethy 1)-1 H-imidazol-4- ylacetic acid hydrochloride (17) and l-(4-Nitrophenyl- methyl)-lH-imidazol-5-ylacetic acid (18) (3:l mixftιre) To a solution of a mixture of l -(4-Nitrophenylmethyl)-lH- imidazol-4-ylacetic acid methyl ester (15) and 1 -(4-Nitrophenylmethyl)- lH-imidazol-5-ylacetic acid methyl ester (16, 3: lmixture, 216 mg, 0.785 mmol) in methanol (3 ml) and tetrahydrofuran (3 ml) under argon was added 1.0 M sodium hydroxide (1.18 ml, 1.18 mmol) and stirred for 18 h. After this time, 1.0 N hydrochloric acid (2.36 ml, 2.36 mmol) was added 5 and the mixture evaporated in vacuo to give the title compounds. !H NMR (CDC13, 400 MHz) δ 9.04 (0.75H, s), 8.83 (0.25H, s), 8.28 (2H, d, J=8.8 Hz), 7.61 (2H, d, J=8.8 Hz), 7.54 (0.75H, s), 7.43 (0.25H, s), 5.61 (0.5H, s), 5.58 (1.5H, s), 3.84 (0.5H, s) and 3.82 (1.5H, s) ppm. l o Step C: Preparation of N-[(2S)-( 1 -(4-Nitropheny Imethyl)- 1 H- imidazol-4-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate (19) and N-[2(S)-(l-(4-Nitrophenyl-methyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - 1 5 naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate (20) To a solution of l-(4-nitrophenylmethyl)-lH-imidazol-4- ylacetic acid hydrochloride (17) and l-(4-nitrophenylmethyl)-lH- imidazol-5-ylacetic acid hydrochloride (18, 3: 1 mixture, 153 mg, 0.392 o mmol), N-[2(S)-amino-3(S)-methylpentyl]-N-naphthylmethyl-glycyl- methionine methyl ester bis hydrochloride (10, 209 mg, 0.392 mmol) and 3-hydroxy-l ,2,3-benzotriazin-4(3H)-one (HOOBT, 64 mg, 0.39 mmol) in methylene chloride (10 ml) was added 1 -(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC, 75.2 mg, 0.392 mmol) and 25 triethylamine (219 μl, 1.57 mmol) and the mixture stirred ovemight at room temperature. After this time, sat. aq. sodium bicarbonate (10 ml) was added and the mixture was extracted with methylene chloride. The combined extracts were washed with sat. aq. sodium bicarbonate (10 ml) and the solvent evaporated in vacuo. The regioisomers were separated 0 by preparative HPLC (chromatography method A ) to give after lyophilization 19 and 20. 19: *H NMR (CD3OD, 400 MHz) δ 8.96 (IH, s), 8.17 (IH, m), 8.23 (2H, d, J=8.7 Hz), 7.92 (2H, d, J=8.9 Hz), 7.61 (IH, d, J=6.9 Hz), 7.56 (2H, d, J=8.9 Hz), 7.50 (2H, m), 7.44 (2H, m), 5.52 (2H, s), 4.70 (IH, d, J=9.4 Hz), 4.49 (IH, d, J=l 1.9 Hz), 4.38 (IH, dd, J=4.7 and 8.9 Hz), 4.13 (IH, m), 3.67 (3H, s), 3.65 (4H, m), 3.30 (IH, m), 3.06 (IH, m), 2.31 (IH, m), 2.23 (IH, m), 1.97 (3H, s), 1.94 (IH, m), 1.71 (IH, m), 1.57 (IH, m), 1.42 (IH, m), 1.17 (IH, m), 0.90 (3H, d, J=6.9 Hz) and 0.87 (3H, t, J=7.4 Hz) ppm. Anal. Calcd for C37H46N6O6S-2.40 TFA-0.25 H2O: C, 51.18; H,5.02; N, 8.57. Found: C, 51.17; H, 5.03; N, 8.80. FAB MS calcd for C37H47N6O6S 703 (MH+), found 703. 20: *H NMR (CD3OD, 400 MHz) δ 8.91 (IH, s), 8.26 (IH, d, J=12.8 Hz), 8.21 (2H, d, J=10.7 Hz), 7.91 (2H, m), 7.65-7.36 (7H, m), 5.51 (2H, s), 4.72-3.99 (4H, m), 3.66 (3H, s), 3.66-3.24 (4H, m), 3.20-2.85 (2H, m), 2.29 (lH, m), 2.20 (lH, m), 1.96 (3H, s), 1.91 (lH, br s), 1.70 (lH, d, J=16 Hz), 1.56 (IH, m), 1.38 (IH, m), 1.13 (IH, m) and 0.88 (6H, m) PPm. FAB HRMS exact mass calcd for C37H47N6O6S 703.32778 (MH+), found 703.32852. Step D: Preparation of N-[2(S)-(1 -(4-Nitropheny Imethy 1)-1 H- imidazol-4-ylacetyl)am o-3(S)-methylpentyl]-N-l- naphthylmethyl-glvcyl-methionine bis trifluoroacetate (21) To a solution of N-[2(S)-(l -(4-nitrophenylmethyl)-lH- imidazol-4-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl- glycy 1-methionine methyl ester bis trifluoroacetate (19, 21 mg, 0.023 mmol) in methanol (1 ml ) at room temperature was added 1.0N lithium hydroxide (135 μl, 0.135 mmol). This solution was stirred for 4 h and treated with trifluoroacetic acid (100 μl). This mixture was purified by preparative HPLC using chromatography method A to give 21. lH NMR (CD3OD, 400 MHz) δ 8.86 (IH, s), 8.23 (2H, d, J= 8.8Hz), 8.22 (IH, m), 7.90 (2H, dd, J=7.3 Hz), 7.55 (2H, d, J=8.4 Hz), 7.44-7.28 (5H, m), 5.50 (2H, s), 4.53 (IH, m), 4.35 (2H, m), 4.12 (IH, m), 3.79- 3.25 (4H, m), 3.26-2.86 (2H, m), 2.27 (IH, m), 2.18 (IH, m), 1.96 (3H, s), 1.9 (IH, m), 1.67 (IH, m), 1.57 (IH, m), 1.42 (IH, m), 1.15 (IH, m), 0.90 (3H, d, J=6.9 Hz) and 0.86 (3H, t, J=7.3 Hz) ppm. FAB HRMS exact mass calcd for C36H45N6O6S 689.31213 (MH+), found 689.31262. Step E: Preparation of N-[2(S)-(l-(4-NitrophenylmethyI)-lH- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glvcyl-methionine bis trifluoroacetate (22) To a solution of N- [2(S)-N'-(1 -(4-nitropheny Imethy 1)-1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N-l-naphthylmethyl- glycyl-methionine methyl ester bis trifluoroacetate (20, 29 mg, 0.031 mmol) in methanol (1 ml ) was added 1.0N lithium hydroxide (187 μl, 0.187 mmol ). This solution was stirred for 4 h and treated with trifluoroacetic acid (100 μl). This mixture was purified by preparative HPLC using chromatography method A to give 22. *H NMR (CD3OD, 400 MHz) δ 8.89 (IH, s), 8.25 (IH, m), 8.21 (2H, d, J= 9.0Hz), 7.89 (2H, m), 7.64-7.34 (7H, m), 5.52 (2H, s), 4.59-3.88 (4H, m), 3.77-3.38 (4H, m), 3.18-2.75 (2H, m), 2.27 (IH, m), 2.18 (IH, m), 1.96 (3H, s), 1.9 (IH, m), 1.67 (IH, m), 1.57 (IH, m), 1.42 (IH, m), 1.15 (lH, m), 0.89 (6H, m) ppm. FAB HRMS exact mass calcd for C36H45N6O6S 689.31213 (MH+), found 689.31135. EXAMPLE 3 Regioselective preparation of N-[2(S)-(l-(4-Nitrophenylmethyl)-lH- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glvcyl-methionine methyl ester bis trifluoroacetate (20) Step A: Preparation of 1 -(Tripheny Imethy 1)- 1 H-imidazol-4-ylacetic acid methyl ester (23) To a suspension of lH-imidazole-4-acetic acid methyl ester hydrochloride (1, 7.48, 42.4 mmol) in methylene chloride (200 ml) was added triethylamine (17.7 ml, 127 mmol) and triphenylmethyl bromide (16.4 g, 50.8 mmol) and stirred for 72 h. After this time, reaction mixture was washed with sat. aq. sodium bicarbonate (100 ml) and water (100 ml). The organic layer was evaporated in vacuo and purified by flash chromatography (30-100% ethyl acetate/hexanes gradient elution) to provide 23 as a white solid. IH NMR (CDC13, 400 MHz) δ 7.35 (IH, s), 7.31 (9H, m), 7.22 (6H, m), 6.76 (IH, s), 3.68 (3H, s) and 3.60 (2H, s) ppm. Step B: Preparation of l-(4-Nitrophenylmethyl)-lH-imidazol-5- ylacetic acid methyl ester (16) To a solution of 1 -(triphenylmethyl)- lH-imidazol-4-ylacetic acid methyl ester (23, 274 mg, 0.736 mmol) in acetonitrile (10 ml) was added 4-nitrobenzylbromide (159 mg, 0.736 mmol) and heated to 55°C for 16 h. After this time, the reaction was cooled to room temperature, treated with ethyl acetate (20 ml) and the resulting precipitate was filtered. The filtrate was concentrated to dryness in vacuo and the residue was redissolved in acetonitrile (4 ml) and heated to 65°C for 3 h. After this time, the reaction mixture was evaporated to dryness and combined with initial precipitate. This residue was dissolved in methanol (5 ml ) and heated to reflux for 30 min. The resulting solution was evaporated in vacuo and the residue was purified by flash chromatography (2-5% methanol/methylene chloride gradient elution ) to provide 16. !H NMR (CDC13, 400 MHz) δ 8.20 (2H, d, J=8.8 Hz), 7.53 (IH, s), 7.19 (2H, d, J=8.8 Hz), 7.03 (IH, s), 5.28 (2H, s), 3.61 (3H, s) and 3.44 (2H, s) PP m - Step C: Preparation of 1 -(4-Nitropheny Imethy 1)- 1 H-imidazol-5 - ylacetic acid hydrochloride (18) - 111 - 1 -(4-Nitrophenylmethyl)- 1 H-imidazol-5-ylacetic acid methyl ester (0.115 g, 0.42 mmol ) was dissolved in 1.0N hydrochloric acid (10 ml ) and heated at 55°C for 3 h. The solution was evaporated in vacuo to give 18 as a white solid. 5 iH NMR (CD3OD, 400 MHz) δ 9.06 (IH, s), 8.27 (2H, d, J=8.8 Hz), 7.61 (IH, s), 7.55 (2H, d, J=8.8 Hz), 5.63 (2H, s) and 3.81 (2H, s) ppm. Step D: Preparation of N-[2(S)-( 1 -(4-Nitropheny Imethy 1)- 1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - 10 naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate (20) Following the procedure described in Example 2, Step C, but using the l -(4-nitrophenylmethyl)-lH-imidazol-5-ylacetic acid hydrochloride, prepared as described in Step C provided the title 15 compound. EXAMPLE 4 Preparation of N-[2(S)-(l-(2-Naphthylmethyl)- lH-imidazol-5- 2 0 ylacetyl)amino-3(S)-methylρentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-( 1 -(2-Naphthylmethy 1)- 1 H-imidazol- 5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - 25 glycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps B-D, but using 2-(bromomethyl)naphthlene in place of 4-nitrobenzylbromide provided the title compound. 30 iH NMR (CD3OD, 400 MHz) δ 8.89 (IH, s), 8.29 (IH, d, J=9 Hz), 7.92 (4H, m), 7.83 (IH, d, J=9 Hz), 7.68 (IH, s), 7.58-7.42 (7H, m), 7.33 (IH, d, J=9 Hz), 5.54 (2H, s), 4.90-4.50 (2H, m), 4.38 (IH, m), 4.05 (IH, m), 3.93-3.32 (5H, m), 3.65 (3H, s), 3.12 (IH, m), 2.24 (2H, m), 1.93 (3H, s), 1.87 (IH, br s), 1.72 (IH, br s), 1.52 (IH, br s), 1.38 (IH, br s), 1.13 (I br s) and 0.87 (6H, m) ppm. Anal. Calcd for C4lH49N5θ4S«3.20 TFA-0.75 H2θ: C, 52.41; H, 4.9 N, 6.45. Found: C, 52.40; H, 4.96; N, 6.63. FAB HRMS exact mass calcd for C41H50N5O4S 708.358352 (MH+), found 708.357618. Step B: Preparation of N-[2(S)-(l-(2-Naphthylmethyl)-lH- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glvcyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Step E, using the methyl ester prepared as described in Step A provided the titl compound. iH NMR (CD3OD, 400 MHz) δ 8.88 (IH, s), 8.28 (IH, d, J=9 Hz), 7.96-7.78 (5H, m), 7.67 (IH, s), 7.57-7.41 (7H, m), 7.32 (IH, d, J=9 Hz 5.55 (2H, s), 4.81(1H, m), 4.56 (IH, m), 4.37 (IH, m), 4.06 (IH, m), 3.89-3.50 (4H, m), 3.42 (IH, m), 3.10 (IH, m), 2.28 (IH, m), 2.19 (IH, m), 2.03-1.86 (lH, m), 1.93 (3H, s), 1.90 (lH, m), 1.71 (lH, m), 1.52 (IH, m), 1.37 (IH, m) and 0.87 (6H, m) ppm. Anal. Calcd for C40H47N5O4S-2.95 TFA-0.5 H2O: C, 53.05; H, 4.94; N, 6.74. Found: C, 53.03; H, 4.95; N, 7.10. FAB HRMS exact mass calcd for C40H48N5O4S 694.342702 (MH+), found 694.342837. EXAMPLE 5 Preparation of N-[2(S)-(1-(1 -Naphthylmethyl)- lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthy Imethy 1-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-^SMl-U-NaphthylmethyD-lH-imidazo S-ylacety ammo-S^-memylpentyll-N-l-naphthylmethyl- lycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps A-D, but using 1 -(bromomethyl)naphthlene in place of 4-nitrobenzylbromide provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.42 (IH, s) 8.31 (IH, d, J=8.9 Hz), 8.04-7.80 (5H, m), 7.69 (IH, m), 7.59-7.39 (7H, m), 7.20 (IH, d, J=8.2 Hz), 5.80 (2H, s), 5.0-4.5 (2H, m), 4.26 (IH, m), 4.13 (IH, m), 4.0-3.6 (4H, m), 3.64 (3H, s), 3.49 (IH, m), 3.18 (IH, m), 2.17 (2H, m), 1.91 (3H, s), 1.86 (IH, m), 1.67 (IH, m), 1.55 (IH, m), 1.41 (IH, m), 1.16 (IH, br s), and 0.88 (6H, m) ppm. 0 Anal. Calcd for C4lH49N5O4S « 3.10 TFA«0.55 H2O: C, 52.92; H, 5.01 ; N, 6.54. Found: C, 52.90; H, 4.99; N, 6.59. FAB HRMS exact mass calcd for C41H50N5O4S 708.358352 (MH+), found 708.357618. 5 Step B: Preparation of N-[2(S)-( 1 -( 1 -Naphthylmethyl)- 1 H-imidazol- 5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - lvcyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Step E, but using the methyl ester prepared as described in Step A provided the title 0 compound. iH NMR (CD3OD, 400 MHz) δ 8.41 (IH, s), 8.19 (IH, d, J=7.7 Hz), 7.99 (2H, m), 7.87 (3H, m), 7.64 (IH, m), 7.56 (IH, t, J=7 Hz), 7.46 (6H, m), 7.16 (IH, d, J=8 Hz), 5.79 (2H, s), 5.04-4.71 (IH, m), 4.61-4.38 (IH, m), 4.38-4.21 (IH, m), 4.14 (IH, m), 3.97-3.51 (4H, m), 3.51 -3.21 (IH, 5 m), 3.21-2.85 (IH, m), 2.21 (IH, m), 2.13 (IH, m), 1.98 (IH, m), 1.91 (3H, s), 1.66 (IH, m), 1.56 (IH, m), 1.40 (IH, m), 1.15 (IH, m), and 0.87 (6H, m) ppm. Anal. Calcd for C40H47N5O4S-2.70 TFA-0.5 H2O: C, 53.95; H, 5.06; N, 6.93. Found: C, 53.97; H, 5.06; N, 7.10. o FAB HRMS exact mass calcd for C40H48N5O4S 694.342702 (MH+), found 694.342837. EXAMPLE 6 Preparation of N-[2(S)-(l-Famesyl-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthylmethyl-glycyl-methionine bis trifluoroacetate Step A: Preparation of 1 -Famesyl- 1 H-imidazol-5-y lacetic acid methyl ester To a solution of 1 -(triphenylmethyl)- lH-imidazol-4-y lacetic acid methyl ester (200 mg, 0.523 mmol) in acetonitrile (5 ml) was added trans, trans-famesyl bromide (156 μl, 0.575 mmol) and heated at 55°C for 16 h. After this time, the reaction was heated at 80°C for 3 h and then the reaction mixture was evaporated in vacuo. The residue was dissolved in methanol (5 ml ) and heated to reflux for 30 min and then evaporated in vacuo. The residue was purified by flash chromatography (2-4% methanol/methylene chloride gradient elution) to provide the title compound. !H NMR (CDC13, 400 MHz) δ 7.50 (IH, s), 6.92 (IH, s), 5.24 (IH, t, J=5.9 Hz), 5.09 (2H, m), 4.49 (2H, d, J=6.9 Hz), 3.69 (3H, s), 3.60 (2H, s), 1.91-2.15 (8H, m), 1.72 (3H, s), 1.65 (3H, s), 1.59 (3H, s) and 1.57 (3H, s) ppm. Step B: Preparation of N-[2(S)-(l-(l-Farnesyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glvcyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps C-D, but using 1 -famesyl- lH-imidazol-5-ylacetic acid methyl ester described in Step A in place of l-(4-nitrophenylmethyl)-lH-imidazol-5-ylacetic acid methyl ester provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.70 (IH, s), 8.26 (IH, m), 7.91 (2H, m), 7.52 (3H, m), 7.48 (IH, m), 7.37 (IH, s), 5.40 (IH, m), 5.08 (2H, m), 4.94-4.72 (3H, m), 4.71 (IH, m), 4.40 (IH, m), 4.13 (IH, m), 3.95-2.80 (6H, m), 3.68 (3H, s), 2.27 (IH, m), 2.21 (IH, m), 2.09 (8H, m), 1.97 (3H, s), 1.92 (2H, m), 1.72 (3H, s), 1.65 (IH, m), 1.65 (3H, s), 1.60 (3H, s), 1.58 (3H, s), 1.42 (IH, m), 1.18 (IH, m) and 0.90 (6H, m) ppm. FAB HRMS exact mass Calcd for C45H66N5O4S 772.483553 (MH+), found 772.481709. Step C: Preparation of N-[2(S)-[ 1 -( 1 -Famesyl)- 1 H-imidazol-5- ylacetyl]amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - lycyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Step E, but using the methyl ester prepared as described in Step B provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.68 (IH, s), 8.18 (IH, m), 7.90 (2H, m), 7.52 (3H, m), 7.44 (IH, t, J=7.5 Hz), 7.37 (IH, s), 5.29 (IH, br t, J=7 Hz), 5.08 (2H, m), 4.95-4.64 (IH, m), 4.73 (2H, m), 4.37 (2H, m), 4.12 (lH, m), 3.71 (2H, m), 3.47 (2H, m), 3.11 (IH, m), 2.95 (IH, m), 2.27 (lH, m), 2.23-2.01 (9H, m), 2.01-1.89 (lH, m), 1.97 (3H, s), 1.77-1.54 (2H, m), 1.71 (3H, s), 1.65 (3H, s), 1.60 (3H, s), 1.58 (3H, s), 1.42 (IH, m), 1.16 (IH, m), 0.91 (3H, t, J=7 Hz) and 0.87 (3H, d, J=7.5 Hz) ppm. FAB HRMS exact mass calcd for C44H64N5O4S 758.467903 (MH+), found 758.467591. EXAMPLE 7 Preparation of N-[2(S)-(l-Geranyl-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-(1 -Geranyl- 1 H-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 6, Steps A-B, but using trans-geranyl bromide in place of famesyl bromide provided the title compound. lH NMR (CD3OD, 400 MHz) δ 8.67 (IH, s), 8.27 (IH, m), 7.92 (2H, m), 7.57 (IH, m), 7.53 (2H, m), 7.46 (IH, dd, J=9 Hz), 7.36 (IH, s), 5.29 (IH, t, J=6 Hz), 5.08 (IH, t, J=6 Hz), 4.71 (IH, m), 4.71-4.12 (IH, m), 4.38 (IH, m), 4.12 (IH, m), 3.80-3.33 (4H, m), 3.68 (3H, s), 3.14 (IH, m), 2.96 (IH, m), 2.29 (IH, m), 2.21 (IH, m), 2.12 (4H, m), 2.11 (IH, m), 1.97 (3H, s), 1.97 (IH, m), 1.70 (3H, s), 1.68 (3H, s), 1.65 (IH, m), 1.60 (3H, s), 1.41 (IH, m), 1.15 (IH, m), 0.91 (3H, d, J=7 Hz) and 0.88 (3H, t, J=7.5 Hz) ppm. Anal. Calcd for C40H57N5O4S-1.80 TFA-0.25 H2O: C, 57.31 ; H, 6.54; N, 7.66. Found: C, 57.28; H, 6.54; N, 7.90. FAB HRMS exact mass calcd for C40H58N5O4S 704.420953 (MH+), found 704.420223. Step B: Preparation of N-[2(S)-( 1 -Geranyl- 1 H-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - lycyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Step E, but using the methyl ester prepared as described in Step A provided the title compound. lH NMR (CD3OD, 400 MHz) δ 8.67 (IH, s), 8.27 (IH, m), 7.92 (2H, m), 7.59 (IH, m), 7.52 (2H, m), 7.46 (IH, t, J=7.8 Hz), 7.38 (IH, s), 5.28 (IH, t, J=l 1.2 Hz), 5.04 (IH, m), 4.96-4.54 (IH, m), 4.72 (2H, s), 4.54- 4.31 (IH, m), 4.39 (IH, m), 4.13 (IH, m), 3.82-3.31 (4H, m), 3.68 (2H, m), 3.31-2.79 (2H, m), 2.30 (IH, m), 2.12 (5H, m), 1.97 (3H, s), 1.97 (IH, m), 1.73 (IH, m), 1.71 (3H, s), 1.70 (3H, s), 1.60 (3H, s), 1.44 (IH, m), 1.18 (IH, m) and 0.92 (3H, d, J=6.8 Hz), and 0.90 (3H, t, J=7.5 Hz) ppm. FAB HRMS exact mass calcd for C39H56N5O4S 690.405303 (MH+), found 690.405157. EXAMPLE 8 Preparation of N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- 5 methionine tris trifluoroacetate (28) and N-[2(S)-(l-(4-Pyridylmethyl)- 1 H-imidazol-5-ylacetyl)amino-(3S)-methylpentyl]-N- 1 -naphthylmethyl; glvcyl-methionine tris trifluoroacetate (29) Step A: Preparation of l-(4-Pyridylmethyl)-lH-imidazol-4-ylacetic i o acid methyl ester (24) and 1 -(4-Pyridy Imethyl)- 1 H-imidazol- 5-ylacetic acid methyl ester (25) (3: 1 mixture) To a solution of sodium hydride (60% in mineral oil, 99 mg, 2.5 mmol) in dimethylformamide (2 ml) cooled at 0°C over ice bath was added, via cannula, a solution of lH-imidazole-4-acetic acid methyl ester 15 hydrochloride (1, 115 mg, 0.707 mmol) in dimethylformamide (2 ml). The suspension was stirred at 0°C for 15 min. This suspension was added to a solution prepared by adding 4-picolyl chloride hydrochloride (185 mg, 0.707 mmol) to sodium hydride (60% in mineral oil, 45.2 mg, 1.13 mmol) in dimethylformamide (2 ml ) at 0°C. After the addition was 0 complete, the mixture was stirred at 0°C for 15 min and then at room temperature for 1.5 h. After this time, the mixture was quenched with sat. aq. sodium bicarbonate (50 ml) and extracted with methylene chloride (2 X 50 ml). The combined organic extracts were washed with brine (50 ml), dried(MgS04), filtered and the solvent evaporated in 5 vacuo. The residue was purified by flash chromatography( 3-7% methanol/methylene chloride gradient elution) to give a 3:1 mixture of 24 and 25. *H NMR (CDCL3, 400MHz) δ 8.57 (1.5H, d, J=5 Hz), 8.56 (0.5H, d, J=7 Hz), 7.51 (0.25H, s), 7.46 (0.75H, s), 7.01 (0.25H, s), 6.99 (1.5H, d, 0 J=5 Hz), 6.90 (0.5H, d, J=7 Hz), 6.86 (0.75H, s), 5.17 (0.5H, s), 5.08 (1.5H, s), 3.69 (2.25H, s), 3.64 (1.5H, s), 3.58 (0.75H, s) and 3.43 (0.5H, s) ppm. Step B: Preparation of N-[2(S)-( 1 -(4-Pyridylmethyl)- 1 H-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glycyl-methionine methyl ester tris trifluoroacetate (26) and N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl- glvcyl-methionine methyl ester tris trifluoroacetate (27) Following the procedure described in Example 2, Steps B-C, but using the mixture of pyridylmethylimidazolylacetic acid from Step A provided the title compounds after preparative HPLC. 26: !H NMR (CD3OD, 400 MHz) δ 8.99 (IH, s), 8.65 (2H, d, J=4.9 Hz), 8.28 (IH, d, J=9.4 Hz), 7.91 (2H, m), 7.69 (IH, d, J=6.5 Hz), 7.61- 7.44 (6H, m), 5.59 (2H, s), 4.90 (IH, m), 4.68 (IH, d, J=13.4 Hz), 4.42 (IH, m), 4.16 (IH, m), 3.90 (IH, d, J=15.6 Hz), 3.82 (IH, d, J=15.6 Hz), 3.75-3.55 (2H, m), 3.69 (3H, s), 3.50 (IH, d, J=13.1 Hz), 3.20 (IH, m), 2.37 (IH, m), 2.29 (IH, m), 1.99 (3H, s), 1.96 (IH, m), 1.77 (IH, m), 1.58 (IH, m), 1.23 (IH, m), 1.19 (IH, m) and 0.91( 6H, m) ppm. Anal. Calcd for C36H46N6θ4S-4.95 TFA-2.2 H2θ: C, 43.65; H, 4.42; N, 6.65. Found: C, 43.65; H, 4.16; N, 6.68. FAB HRMS exact mass calcd for C36H47N6O4S 659.337951 (MH+), found 659.336943 27: iH NMR (CD3OD, 400 MHz) δ 9.01 (IH, s), 8.63 (2H, m), 8.28 (IH, m), 7.98 (2H, m), 7.70 (IH, d, J=6.0 Hz), 7.52 (4H, m), 7.41 (2H, d, J=6.2 Hz), 5.62 (2H, s), 4.94 (IH, m), 4.72 (IH, m), 4.42 (IH, m), 4.07 (IH, m), 3.89 (2H, m), 3.68 (lH,m), 3.69 (3H, s), 3.55 (2H, m), 3.24 (IH, m), 2.39 (IH, m), 2.31 (IH, m), 2.00 (3H, s), 1.98 (IH, m), 1.79 (IH, m), 1.58 (IH, m), 1.42 (IH, m), 1.18 (IH, m) and 0.91 (6H, m) ppm. FAB HRMS exact mass calcd for C36H47N6O4S 659.337951 (MH+), found 659.336826. Step C: Preparation of N-[2(S)-(1 -(4-Pyridylmethyl)-lH-imidazol-4- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glycyl-methionine methyl ester tris trifluoroacetate (28) Following the procedure described in Example 2, Step D, but using the methyl ester 26 prepared as described in Step B provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.96 (IH, s), 8.55 (2H, d, J=5.2Hz), 8.21 (IH, d, J=7.2 Hz), 7.97 (2H, m), 7.69 (IH, d, J=7.2 Hz), 7.60-7.40 (6H, m), 5.58 (2H, s), 4.91 (IH, d, J=13.2 Hz), 4.69 (IH, d, J=13.2 Hz), 4.38 (IH, dd, J=4.6 and 8.8 Hz), 4.15 (IH, m), 3.89 (IH, d, J=16.1 Hz), 3.81 (IH, d, J=16.1 Hz), 3.71 (lH, d, J=17 Hz), 3.62 (IH, d, J=17 Hz), 3.50 (IH, dd, J=3.4 and 12 Hz), 3.21 (IH, m), 2.38 (IH, m), 2.27 (IH, m), 1.99 (IH, m), 1.99 (3H, s), 1.77 (IH, m), 1.58 (IH, m), 1.43 (I H, m), 1.16 (lH, m), and 0.88 (6H, m) ppm. FAB HRMS exact mass calcd for C35H45N6O4S 645.322301 (MH+), found 645.323649. Step D: Preparation of N-[2(S)--(l -(4-Pyridy Imethyl)- lH-imidazol- 5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - glvcyl-methionine tris trifluoroacetate (29) Following the procedure described in Example 2, Step E, but using the methyl ester 27 prepared as described in Step B provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.97 (IH, s), 8.58 (2H, s), 8.27 (IH, m), 7.95 (2H, m), 7.64 (IH, m), 7.50 (4H, m), 7.31 (2H, d, J=4.4 Hz), 5.57 (2H, s), 4.63 (2H, m), 4.38 (IH, m), 4.09 (IH, m), 3.78 (2H, m), 3.60 (2H, m), 3.42 (IH, m), 3.15 (IH, m), 2.36 (IH, m), 2.15 (IH, m), 2.01 (IH, m), 1.98 (3H, s), 1.76 (IH, m), 1.55 (IH, m), 1.41 (IH, m), 1.15 (IH, m) and 0.88 (6H, m) ppm. FAB HRMS exact mass calcd for C35H45N6O4 645.322301 (MH+), found 645.321321. EXAMPLE 9 Preparation of N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthy Imethy 1-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-( 1 -(4-Cyanophenylmethyl)- 1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps B-D, but using a-bromo-p-tolunitrile in place of 4-nitrobenzylbromide provided the title compound. !H NMR (CD3OD, 400 MHz) δ 8.92 (IH, s), 8.31 (IH, m), 8.01 (IH, d, J=8 Hz), 7.96 (IH, m), 7.75 (2H, d, J=8 Hz), 7.62 (IH, s), 7.58-7.48 (3H, m), 7.45 (IH, m), 7.41 (2H, d, J=8 Hz), 5.51 (2H, s), 4.97 (IH, m), 4.76 (IH, m), 4.41 (IH, m), 4.10 (IH, m) 3.92 (2H, m), 3.75-3.47 (3H, m), 3.69 (3H, s), 3.25 (IH, m), 2.37 (IH, m), 2.30 (IH, m), 2.00 (3H, s), 1.97 (lHjn), 1.79 (IH, m), 1.58 (IH, m), 1.43 (IH, m), 1.19 (IH, m) and 0.91 (6H, m) ppm. Anal. Calcd for C38H46N6O4S-2.40 TFA-1.90 H2O: C, 51.89; H, 5.31 ; N, 8.48. Found: C, 51.88; H, 5.29; N, 8.72. FAB HRMS exact mass calcd for C38H47N6O4S 683.337951 (MH+), found 683.338437. Step B: Preparation of N-[2(S)-( 1 -(4-Cyanophenylmethyl)- 1 H- imidazol-5-y lacety l)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glvcyl-methionine bis trifluoroacetate To a solution of N-[2(S)-(l-(4-cyanophenylmethyl)-lH- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl- glycyl-methionine methyl ester bis trifluoroacetate (25.6 mg, 0.028 mmol) in methanol (1 ml ) was added 1.0N sodium hydroxide (280 μl, 0.280 mmol) and stirred for 2 h. After this time, the mixture was treated with trifluoroacetic acid (to pH <3) and purified by preparative HPLC (chromatography method A) to give after lyophilization, the title compound. iH NMR (CD3OD, 400 MHz) δ 8.87 (IH, s), 8.27 (IH, d, J=9.2 Hz), 7.90 (2H, m), 7.73 (2H, d, J=8 Hz), 7.60 (IH, s), 7.46 (4H, m), 7.36 (2H, d, J=8 Hz), 5.48 (2H, s), 4.95-4.28 (2H, m), 4.36 (IH, m), 4.09 (IH, m), 3.59 (4H, m), 3.51-2.73 (2H, m), 2.29 (IH, m), 2.19 (IH, m), 2.03-1.85 (lH, m), 1.97 (3H, s), 1.70 (lH, m), 1.56 (lH, m), 1.39 (lH, m), 1.14 (IH, m) and 0.89 (6H, m) ppm. Anal. Calcd for C37H44N604S-2.45 TFA-1.3 H2O: C, 51.80; H, 5.09; N, 8.65. Found: C, 51.78; H, 5.07; N, 8.95. FAB HRMS exact mass Calcd for C37H44N6O4S 669.322301 (MH+), found 669.323148. EXAMPLE 10 Preparation of N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-(1 -(4- Methoxyphenylmethyl)-lH- imidazol-5-yl)acetyl)amino-3(S)-methylpentyl]-N-l- naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps B-D, but using 4-methoxybenzyl chloride in place of 4-nitrobenzylbromide provided the title compound. !H NMR (CD3OD, 400 MHz) δ 8.70 (IH, s), 8.27 (IH, m), 7.92 (2H, m), 7.70-7.35 (5H, m), 7.18 (2H, d, J=8.5 Hz), 6.92 (2H, d, J=8.5 Hz), 5.27 (2H, s), 4.60-4.00 (4H, m), 3.79 (3H, s), 3.67 (3H, s), 3.61 (4H, m), 3.40-2.75 (2H, m), 2.28 (IH, m), 2.19 (IH, m), 1.96 (3H, s), 1.91 (IH, m), 1.70 (IH, m), 1.60 (IH, m), 1.43 (IH, m), 1.18 (IH, m) and 0.91 (6H, m) ppm. Anal. Calcd for C38H49N5θ5S-1.75 TFA-1.75 H2θ: C, 54.45; H, 5.98; N, 7.67. Found: C, 54.44; H, 5.95; N, 7.85. FAB HRMS exact mass calcd for C38H50N5O5S 688.353267 (MH+), found 688.352186. Step B: Preparation of N-[2(S)-(1 -(4-Methoxyphenylmethy 1)- 1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glvcyl-methionine bis trifluoroacetate Following the procedure described in Example 9, Step B, but substituting the methyl ester from Step A provided the title compound. iH NMR (CD30D, 400 MHz) δ 8.70 (IH, s), 8.27 (IH, m), 7.92 (2H, m), 7.63 (IH, s), 7.56-7.35 (4H, m), 7.18(2H, d, J=8.6 Hz), 6.93 (2H, d, J=8.6 Hz), 5.27 (2H, s), 4.93-4.29 (2H, m), 4.36 (IH, m), 4.12 (IH, m), 3.79 (3H, s), 3.63 (4H, m), 3.07 (2H, m), 2.28 (IH, m), 2.19 (IH, m), 2.02-1.88 (IH, m), 1.95 (3H, s), 1.70 (IH, m), 1.60 (IH, m), 1.43 (IH, m), 1.18 (lH, m) and 0.91 (6H, m) ppm. FAB HRMS exact mass calcd for C37H48N5O5S 674.337617 (MH+), found 674.338053. EXAMPLE 11 Preparation of N-[2(S)-(1 -(4-Quinolinylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-(1 -(4-Quinolinylmethyl)-lH- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N-l- naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 3, Steps B-D, but using 4-(bromomethyI)quinoline hydrochloride in place of 4- nitrobenzylbromide provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.88 (IH, s), 8.83 (IH, d, J=4.8 Hz), 8.28 (IH, m), 8.15 (IH, d, J=8.6 Hz), 7.99-7.85 (4H, m), 7.67 (2H, m), 7.57 (IH, s), 7.48 (3H, m), 6.96 (IH, m), 6.02 (2H, s), 4.90 (IH, m), 4.62 (1H, m), 4.18 (IH, m), 4.07 (IH, m), 3.94-3.50 (4H, m), 3.64 (3H, s), 3.45 (IH, m), 3.13 (IH, m), 2.28 (IH, m), 2.21 (IH, m), 1.95 (3H, s), 1.87 (IH, m), 1.69 (IH, m), 1.48 (IH, m), 1.35 (IH, m), 1.11 (IH, m) and 0.84 (6H, m) ppm. FAB HRMS exact mass calcd for C40H49N6O4S 709.353601 (MH+), found 709.353711. Step B: Preparation of N-[2(S)-( 1 -(4-Quinolinylmethyl)- 1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - naphthylmethyl-glvcyl-methionine bis trifluoroacetate Following the procedure described in Example 9, Step B, but substituting the methyl ester from Step A provided the title compound. !H NMR (CD3OD, 400 MHz) δ 8.87 (IH, s), 8.82 (IH, d, J=5 Hz), 8.28 OH, m), 8.15 (IH, d, J=8.6 Hz),8.06-7.82 (4H, m), 7.67 (2H, m), 7.58 (IH, s), 7.48 (3H, s), 6.96 (IH, m), 6.03 (2H, s), 4.93-4.57 (2H, m), 4.22 (IH, m), 4.08 (IH, m), 3.72 (4H, m), 3.47 (IH, m), 3.13 (IH, m), 2.28 (IH, m), 2.21 (IH, m), 1,95 (3H, s), 1.87 (IH, m), 1.70 (IH, m), 1.48 (IH, m), 1.35 (IH, m), 1.09 (IH, m) and 0.84 (6H, m) ppm. FAB HRMS exact mass calcd for C39H47N6O4S 695.33795 (MH+), found 695.33893. EXAMPLE 12 Preparation of N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N-l -phenylmethyl-glycyl-methionine bis trifluoroacetate Step A: Preparation of N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol- 5-ylacetyl)amino-3(S)-memylpentyl]-N-l-phenylmethyl- lvcyl-methionine methyl ester bis trifluoroacetate To a solution of l-(2-naphthylmethyl)-lH-imidazol-5- ylacetic acid hydrochloride (prepared in Example 4, 75 mg, 0.25 mmol), N-[2(S)-amino-3(S)-methylpentyl]-N-pheny Imethy 1-glycyl-methionine methyl ester bis hydrochloride (prepared analogously to 10, 112 mg, 0.248 mmol) and 3-hydroxy-l,2,3-benzotriazin-4(3H)-one (HOOBT, 44 mg, 0.27 mmol) in dimethylformamide (5 ml) was added l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 52 mg, 0.272 mmol) and triethylamine (171 μl, 1.23 mmol) and the suspension stirred for 3 days. After this time, sat. aq. sodium bicarbonate (10 ml) and water (10 ml) was added and the mixture was extracted with ethyl acetate (2 x 50 ml). The combined extracts were washed with brine (20 ml) and the solvent evaporated in vacuo. Purification by preparative o HPLC (chromatography method A ) gave, after lyophilization, the title compound. iH NMR (CD3OD, 400 MHz) δ 8.94 (IH, s), 7.93 (IH, d, J=8.5 Hz), 7.88 (2H, m), 7.81 (IH, s), 7.55 (5H, m), 7.43 (4H, m), 5.68 (2H, s), 4.60 (IH, m), 4.46 (IH, dd, J=4.5 Hz), 4.27 (IH, d, J=13 Hz), 4.14 (IH, m), 5 3.95 (IH, d, J=15.5 Hz), 3.85 (IH, d, J=15.5 Hz), 3.83 (2H , s), 3.67 (3H, s), 3.48 (IH, d, J=13 Hz), 3.24 (I H, d, J=13 Hz), 2.40 (IH, m), 2.31 (IH, m), 2.00 (IH, m), 1.96 (3H, s), 1.85 (IH, m), 1.57 (IH, m), 1.44 (IH, m), 1.19 (IH, m), 0.93 (3H, d, J=6.7 Hz) amd 0.91 (3H, t, J=7 Hz) ppm. Anal. Calcd for C37H47N504S-2.85 TFA-0.40 H2O: C, 51.80; H, 5.16; 0 N, 7.07. Found: C, 51.80; H, 5.14; N, 7.31. Step B: Preparation of N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol- 5-ylacetyl)amino-3(S)-methylpentyl]-N-l-phenylmethyl- lycyl-methionine bis trifluoroacetate 5 Following the procedure described in Example 9, Steps B, but substituting the methyl ester from Step A provided the title compound. !H NMR (CD3OD, 400 MHz) δ 8.92 (IH, s), 7.93 (IH, d, J=8.6 Hz), 7.87 (2H, m), 7.78 (IH, s), 7.55 (3H, m), 7.43 (2H, m), 7.39 (IH, d, J=8.4Hz), 7.35 (3H, m), 5.67 (2H, s), 4.46 (IH, dd, J=4.5 Hz), 4.41-3.90 (IH, m), 4.11 (IH, m), 4.00 (IH, m), 3.75 (2H, m), 3.64 (2H, m), 3.20 (IH, m), 2.98 (IH, m), 2.43 (IH, m), 2.35 (IH, m), 2.08 (IH, m), 1.97 (3H, s), 1.91 (IH, m), 1.54 (IH, m), 1.40 (IH, m), 1.15 (IH, m) and 0.89 (6H, m) ppm. Anal. Calcd for C36H45N5O4S-2.70 TFA-0.70 H2θ: C, 51.57; H, 5.13; N, 7.26. Found: C, 51.54; H, 5.1 1 ; N, 7.43. FAB HRMS exact mass calcd for C36H46N5O4S 644.327052 (MH+), found 644.326203. EXAMPLE 13 Preparation of N-[2(S)-(1 -(2-Naphthy Imethy l)-lH-imidazol-5- ylethyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine bis trifluoroacetate Step A: Preparation of N-Methoxy-N-methyl-l-(2-naphthylmethyl)- 1 H-imidazol-5- ylacetamide To a solution of l-(2-naphthylmethyl)-lH-imidazol-5- ylacetic acid hydrochloride (prepared in Example 4, 0.819 mg, 2.70 mmol) in dimethylformamide (15 ml ) was added sequentially N, O- dimethylhydroxylamine hydrochloride (293 mg, 3.0 mmol), 3-hydroxy- l,2,3-benzotriazin-4(3H)-one (HOOBT, 489 mg, 3.0 mmol), l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 575 mg, 3.0 mmol) and triethylamine (1.67 ml, 12.0 mmol) and the resulting mixture stirred at room temperature for 18 h. Saturated aq. sodium bicarbonate (30 ml) and water (30 ml) were added and the mixture was extracted with methylene chloride (2 x 50 ml). The combined organic extracts were washed with brine (50 ml) and the solvent evaporated in vacuo. The residue was purified by flash chromatography (2-4% methanol/methylene chloride gradient elution) to provide the title compound as an oil. iH NMR (CDC13, 400 MHz) δ 7.80 (2H, m), 7.74 (IH, m), 7.56 (IH, s), 7.47 (3H, m), 7.22 (IH, d, J=8.6 Hz), 6.97 (IH, s), 5.37 (2H, s), 3.58 (2H, s), 3.51 (3H, s) and 3.12 (3H, s) ppm. Step B: 1 -(2-NaphthylmethvD- 1 H-imidazol-5- ylacetaldehvde (30) To a suspension of lithium aluminum hydride (40.8 mg, 1.07 mmol) in tetrahydrofuran (5 ml) at -45°C was added a solution of N- methoxy-N-methyl- 1 -(2-naphthylmethyl)- 1 H-imidazol-5-ylacetamide (243 mg, 0.895 mmol) in tetrahydrofuran (5 ml) via cannula at such a rate to maintain the temperature at <-35°C. After the addition was complete, the reaction was allowed to warm to +5°C and then recooled to -35°C. To this solution was added a solution of potassium bisulfate (272 mg) in water (1 ml). The mixture was stirred for 30 min at room temperature and then filtered through celite. The celite pad was washed with ethyl acetate (25 ml). The combined filtrates were washed with sat. sodium bicarbonate (10 ml) and then water (10 ml). The organic layer was dried(MgS04), filtered and evaporated in vacuo to give 30 as a clear oil. This material was used as is in the next step. !H NMR (CDC13, 400 MHz) δ 9.50 (IH, t, J=2 Hz), 7.85-7.70 (3H, m), 7.64 (IH, s), 7.53-7.40 (3H, m), 7.16 (IH, d, J=12 Hz), 7.06 (IH, s), 5.20 (2H, s) and 3.53 (2H, m) ppm. Step C: Preparation of N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol- 5-ylethyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl - lvcyl-methionine methyl ester bis trifluoroacetate To a solution of l-(2-naphthylmethyl)-lH-imidazol-5- ylacetaldehyde (116.8 mg, 0.465 mmol) and N-[2(S)-amino-3(S)- methylpentyl]-N-naphthylmethyl-glycyl-methionine methyl ester bis hydrochloride (10, 297 mg, 0.558 mmol) in 1 ,2-dichloroethane (10 ml) and dimethylformamide (5 ml) was added 3A molecular sieves (500 mg) and sodium triacetoxyborohydride (473 mg, 2.23 mmol). This mixture was stirred at room temperature for 18 h. After this time, the mixture was filtered through a sintered glass funnel. The filtrate was diluted with methylene chloride (100 ml) and washed with sat. sodium bicarbonate (50 ml). The organic layer was dried over magnesium sulfate, filtered and the solvent was evaporated in vacuo. The residue was purified first by flash chromatography eluting with 2-5% methanol/methylene chloride and then by preparative HPLC (chromatography method A) to provide the title compound as a white foam. iH NMR (CD3OD, 400 MHz) δ 9.05 (IH, s), 8.10 (IH, d, J=7.5 Hz), 8.02-7.79 (5H, m), 7.75 (IH, s), 7.65-7.27 (7H, m), 7.21 (IH, s), 5.59 (2H, s), 4.65 (IH, dd, J=4.7 and 9.4 Hz), 4.31 (IH, d, J=13 Hz), 4.17 (IH, d, J=13 Hz), 3.69 (3H, s), 3.65 (IH, d, J=17 Hz), 3.55 (IH, d, J=17 Hz), 3.00 (IH, dd, J=3.5 and 14 Hz), 2.93-2.42 (6H, m), 2.33 (IH, m), 2.23 (IH, m), 2.13 (IH, m), 2.06 (3H, s), 1.96 (IH, m), 1.41 (IH, m), 1.07 (2H, m), 0.75 (3H, d, J=6.5 Hz) and 0.70 (3H, t, J=7.5 Hz) ppm. FAB HRMS exact mass calcd for C41H52N5O3S 694.37909 (MH+), found 694.37959. Step D: Preparation of N-[2(S)-( 1 -(2-Naphthylmethy 1)- 1 H-imidazol- 5-ylethyl)ammo-3(S)-methylpentyl]-N-l-naphthylmethyl- lvcyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Steps D, but substituting the methyl ester from Step C provided the title compound. Ϊ H NMR (CD3OD, 400 MHz) δ 8.95 (IH, s), 8.09 (IH, d, J=7.7 Hz), 7.94 (IH, d, J=8.5 Hz), 7.93-7.78 (4H, m), 7.73 (IH, s), 7.62-7.24 (7H, m), 7.17 (IH, s), 5.56 (2H, s), 4.61 (IH, dd, J=4.3 and 10 Hz), 4.31 (IH, d, J=13 Hz), 4.14 (IH, d, J=13 Hz), 3.65 (IH, d, J=17 Hz), 3.55 (IH, d, J=17 Hz), 2.99 (IH, d, J=15 Hz), 2.91-2.43 (6H, m), 2.25-1.91 (4H, m), 2.06 (3H, s), 1.33 (IH, m), 1.01 (2H, m), 0.72 (3H, d, J=6.7 Hz) and 0.65 (3H, t, J=7.5 Hz) ppm. FAB HRMS exact mass calcd for C40H50N5O3S 680.36344 (MH+), found 680.36282 EXAMPLE 14 Preparation of 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester hydrochloride Step A: Preparation of N-(α-chloroacetyl)-L-isoleucinol To a stirred solution of L-isoleucinol (20 g, 0.17 mol) and triethylamine (28.56 ml, 0.204 mol) in CH2CI2 (500 ml) at -78°C was added chloroacetyl chloride (16.3 ml, 0.204 mol) over 5 minutes. The cooling bath was removed and the solution allowed to warm to -20°C. The mixture was diluted with EtOAc and washed sequentially with 1 M HCI, and brine and dried (Na2Sθ4). Evaporation in vacuo afforded the title compound Rf = 0.3 CH2C12: MeOH (95:5); IH NMR (CDCI3) δ 6.80 (IH, brd, J = 5 Hz), 4.10 (2H, s), 3.84 (IH, m), 3.79 (2H, m), 2.65 (IH, brs), 1.72 (IH, m), 1.55 (IH, m), 1.17 (IH, m), 0.96 (3H, d, J = 6Hz) 0.90 (3H,t, J=6 Hz). Step B: Preparation of 5(S)-[1 (S)-methyl]propyl-2,3,5,6-tetra-hydro- 4H-1.4-oxazin-3-one . To a stirred solution of N-(α-chloroacetyl)-L-isoleucinol (68, 7.4 g, 0.038 mol) in THF (125 ml) under argon at 0°C was slowly added sodium hydride (2.2 g of a 60% dispersion in mineral oil, 0.055 mol) with concomitant gas evolution. After completing the addition, the mixture was warmed to room temperature (R.T.) and stirred for 16 hr. Water (2.8 ml) was added and the solvents evaporated in vacuo. The residue was dissolved in CHCI3 (70 ml) and washed with saturated NaCl solution. The organic layer was dried (Na2S04) and evaporated in vacuo. The residue was chromatographed using silica gel eluting with CH2Cl2-"MeOH (96:4) to afford the title compound as a white solid. Rf = 0.35 CH2Cl2:MeOH (95:5); IH NMR (CDCI3) δ 6.72 (IH, brs), 4.20 (IH, d, J = 14.5 Hz), 4.10 (IH, d, J = 14.5 Hz), 3.88 (IH, dd, J = 9 and 3.5 Hz), 3.58 (IH, dd, J = 9 and 6.5 Hz), 3.45 (IH, brqt, J = 3.5 Hz), 1.70-1.45 (2H, m), 1.34 - 1.15 (IH, m), 0.96 (3H, t, J = 6.5 Hz), 0.94 (3H, d, J = 6.5 Hz). Step C: Preparation of N-(tert-butoxycarbonyl)-5(S)-[l (S)- methyllpropyl-2.3.5.6-tetrahydro-4H-1.4-oxazin-3-one. 5(S)-[l(S)-Methyl]propyl-2,3,5,6-tetrahydro 4H-l,4-oxazin- 3-one (12.2 g, 0.0776 mol) and DMAP (18.9 g, 0.155 mol) were dissolved in methylene chloride (120 ml) under argon at room temperature. Boc anhydride (33.9 g, 0.155 mol) was added to the stirred solution in one portion, with concomitant gas evolution and the mixture was stirred at for 16 hr. The solvent was evaporated in vacuo and the residue was taken up in ethyl acetate and washed sequentially with 10% citric acid, 50% NaHC03 and finally brine. The organic extract was dried (Na2Sθ4) and evaporated in vacuo. Chromatography of the residue over silica gel eluting with 20% EtOAc in hexanes afforded the title compound as a white solid. Rf = 0.75 EtOAc:hexanes (20:80); mp 59-60°C Anal. Calcd for C13H23O4N : C, 60.68; H,9.01 ; N, 5.44. Found: C, 60.75; H, 9.01 ; N, 5.58. IH NMR (CDCI3) δ 4.25 (IH, d, J = 15 Hz), 4.15 (IH, d, J = 15 Hz), 4.15 - 4.00 (2H, m), 3.73 (IH, dd, J = 10 and 2 Hz), 1.88 (IH, qt, J = 6 Hz), 1.55 (9H, s), 1.50 - 1.36 (l H, m), 1.35 - 1.19 (l H, m), 1.00 (3H, d, J = 6 Hz), 0.95 (3H, d, J = 6.5 Hz). Step D: Preparation of N-(tert-Butoxycarbonyl)-2(S)-benzyl-5(S)- [ 1 (S)-methyl]propyl-2,3,5,6-tetrahydro-4H-l ,4-oxazin-3- one A solution of N-(tert-butoxycarbonyl)-5(S)-[l(S)- methyl]propyl-2,3,5,6-tetrahydro-4H-l ,4-oxazin-3-one (5.75 g, 22.3 mmol) in DME (100 ml) under argon was cooled to -60°C. The cold solution was transferred via canula to a second flask containing sodium bis(trimethylsilyl)amide (24.58 ml of a IM solution in THF, 24.58 mmol) at -78°C under argon. After stirring for 10 minutes, benzyl bromide (2.25 ml, 19.0 mmol) was added over 5 minutes and the resulting mixture was stirred at -78°C for 3 hours. After this time, the reaction mixture was transferred via cannula to another flask containing sodium bis(trimethylsilyl)amide (24.58 ml of a IM solution in THF, 24.58 mmol) at -78°C, under argon. After stirring for a further 5 minutes, the reaction was quenched by the addition of saturated aqueous ammonium chloride solution (24.6 ml) and allowed to warm to room temperature. This mixture was diluted with brine (50 ml) and water (20 ml) and then extracted with ethyl acetate (2 x 100 ml). The organic extracts were washed with brine (50 ml) and evaporated in vacuo to afford an oil. Chromatography of the residue over silica gel (230-400 mesh, 300 g) eluting with 10-20% ethyl acetate in hexanes afforded the title compound as a clear oil. Rf = 0.25 EtOAc:Hexanes (20:80); IH NMR (CDC13) δ 7.35 - 7.15 (5H, m), 4.31 (IH, dd, J = 6 and 2 Hz), 4.03 (IH, d, J = 12 Hz), 3.88 (IH, dd, J = 6 and 1 Hz), 3.66 (IH, dd, J = 12 and 2 Hz), 3.29 (IH, dd, J = 12 and 3 Hz), 1.54 (9H, s), 3.12 (IH, dd, J = 12 and 7 Hz), 1.47 (IH, m), 1.25 (IH, m), 1.10 (IH, m), 0.83 (3H, d, J = 6 Hz), 0.80 (3H, t, J = 6 Hz). Step E: Preparation of N-(tert-butoxycarbonyl)-2(S)-[2(S)-amino- 3(S)-methyllpentyloxy-3-phenyl-propionic acid To a stirred solution of N-(tert-butoxycarbonyl)-2(S)-benzyl- 5(S)-[l (S)-methyl]-propyl-2,3,5,6-tetrahydro-4H-l,4-oxazin-3-one (5.1 g, 14.7 mmol) in THF (150 ml) and water (50 ml) at 0°C was added hydrogen peroxide (15 ml of a 30% aqueous solution, 132 mmol) and lithium hydroxide (3.0 g, 63.9 mmol). After stirring for 30 minutes, the reaction was quenched with a solution of sodium sulfite (28.25 g, 0.224 mol) in water (70 ml). The THF was evaporated in vacuo and the aqueous phase was acidified to pH 3-4 by addition of 10% citric acid solution and extracted with EtOAc. The organic extracts were dried (Na2Sθ4), evaporated in vacuo and the residue purified by chromatography over silica gel eluting with 4% MeOH in CH2CI2 to give 2(S)-benzyl-5(S)-[ 1 (S)-methyl]propyl-2,3,5,6-tetrahydro-4H- 1 ,4- oxazin-3-one and then with 20% MeOH in CH2CI2 to afford the title compound as a white solid (pet ether, mp 68-70°C). Rf = 0.4 MeOH:CH2Cl2 (5:95) + 0.3% AcOH; lH NMR (d6 DMSO) δ 7.35 - 7.10 (5H, m), 6.68 (IH, br, s), 3.75 (IH, dd, J = 7.5 and 2.5 Hz) 3.54 (IH, m), 3.5 - 3.2 (2H, m) 2.99 (IH, dd, J = 12.5 and 2.5 Hz), 2.75 (IH, dd, J = 12.5 and 7.5 Hz), 1.50 - 1.35 (1 IH, m), 0.98 (IH, sept, J = 6 Hz), 0.78 (3H, t, J = 6 Hz), 0.65 (3H, d, J = 6 Hz); FAB MS 366 (MH+) 266 (MH2+ - Cθ2tBu). Step F: Preparation of N-(tert-Butoxycarbonyl)-2(S)-[2(S)-amino- 3(S)-methyl]-pentyloxy-3-phenyl-propionyl-methione sulfone methyl ester The title compound was prepared by EDC coupling of N- (tert-butoxycarbonyl)-2(S)-[2(S)-amino-3(S)-methyl]pentyloxy-3- phenylpropionic acid with methionine sulfone methyl ester. IH NMR (CD3OD) δ 0.80 (3H, d, J=6 Hz), 0.88 (3H, t, J=6 Hz), 1.12 (IH, m), 1.40-1.55 (lH,m), 1.47 (9H, s), 2.10 (IH, m), 2.32 (I H, m), 2.80-3.10 (4H,m), 2.93 (3H, s), 3.40 (lH,m), 3.5-3.7 (2H, m), 3.74 (3H, s), 4.01 (H, m), 4.60 (H, m), 6.60 (H, d, J=8 Hz), 7.25 (5H, m). Step G: Preparation of 2(S)-[2(S)-Amino-3(S)-methyl]pentyloxy-3- phenylpropionyl-methionine sulfone methyl ester hydrochloride N-(tert-butoxycarbonyl-2(S)-[2(S)-amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester was treated with HCI gas in ethyl acetate and the solvent was evaporated in vacuo to afford the title compound. Ϊ H NMR (CD3OD) δ 0.85 (3H, d, J=6 Hz), 0.94 (3H, t, J=6 Hz), 1.20 (IH, m), 1.52 (IH, m), 1.72 (IH, m), 2.14 (IH, m), 2.38 (IH, m), 2.98 (3H, s), 2.90-3.20 (4H, m), 3.25 (IH, m), 3.57 (IH, dd, J=12 and 6 Hz), 3.73 (IH, dd, J=12 and 9 Hz), 3.78 (3H, s), 4.15 (IH, m), 4.63 (IH, d, J=8.5 Hz), 7.30 (5H, m). Step H: Preparation of 2(S)-[N-2(S)-( 1 -(2-Naphthy Imethyl)- 1 H- imidazol-5-ylacetyl)amino-3(S)-methyl]pentyloxy-3- phenylpropionyl-methionine sulfone methyl ester hydrochloride To a solution of l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetic acid hydrochloride (prepared in Example 4, 67 mg, 0.21 mmol), 2(S)-[2(S)-amino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester hydrochloride (100 mg, 0.209 mmol) and 3- hydroxy-l,2,3-benzotriazin-4(3H)-one (HOOBT, 37.5 mg, 0.209 mmol) in dimethylformamide (4 ml) was added 1 -(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC, 44 mg, 0.21 mmol) and triethylamine (109 ul, 0.78 mmol) and the suspension stirred ovemight. After this time, sat. aq. sodium bicarbonate (7 ml) was added and the resulting precipitate filtered. The precipitate was partitioned between water (25 ml) and methylene chloride (50 ml). The organic extract was evaporated in vacuo. The residue was purified by flash chromatography eluting with 2-3% methanol/methylene chloride gradient to provide a gum. The gum was dissolved in methanol (5 ml) and treated with gaseous hydrogen chloride to pH=2 and the solution was evaporated in vacuo. The resulting gum was dissolved in methanol (2 ml) and water (20 ml) and lyophilized to give the title compoundas a white foam. !H NMR (CD3OD, 400 MHz) δ 8.93 (IH, s), 8.35 (IH, d, J=8.7 Hz), 8.14 (IH, d, J=8.7 Hz), 7.94 (IH, d, J=8.6 Hz), 7.92-7.83 (2H, m), 7.77 (IH, s), 7.58-7.49 (3H, m), 7.38 (IH, d, J=8.4 Hz), 7.23-7.10 (5H, m), 5.62 (IH, d, J=15.5 Hz), 5.61 (IH, d, J=15.5 Hz), 4.56 (IH, m), 4.05 (IH, dd, J=4.0 and 7.4 Hz), 3.90 (IH, m), 3.70 (2H, s), 3.66 (3H, s), 3.57 (IH, dd, J=3.5 and 9.9 Hz), 3.47 (IH, dd, J=7.0 and 9.9 Hz), 3.04 (IH, dd, J=4.0 and 14.1 Hz), 2.96 (IH, m), 2.91 (IH, dd, J=7.5 and 14.1 Hz), 2.90 (3H, s), 2.80 (IH, m), 2.27 (IH, m), 2.09 (IH, m), 1.50 (IH, m), 1.43 (IH, m), 1.07 (IH, m), 0.84 (3H, t, J=7.4 Hz) and 0.77 (3H, d, J=6.7 Hz) ppm. Anal. Calcd for C37H46N4θ7S-2.3 HCI: C, 57.36; H,6.28; N, 7.23. Found: C, 57.40; H, 6.20; N, 7.38. FAB HRMS exact mass calcd for C37H47N4O7S 691.316547 (MH+), found 691.316460. EXAMPLE 15 Preparation of 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine sulfone trifluoroacetate Following the procedure described in Example 9, Step B, but substituting the methyl ester from Example 14 provided the title compound. lH NMR (CD3OD, 400 MHz) δ 8.93 (IH, s), 8.27 (IH, d, J=8.3 Hz), 8.10 (IH, d, J=9.3 Hz), 7.94 (IH, d, J=8.6 Hz), 7.92-7.83 (2H, m), 7.75 (IH, s), 7.57-7.52 (2H, m), 7.50 (IH, s), 7.37 (IH, d, J=8.6 Hz), 7.23- 7.11 (5H, m), 5.60 (IH, d, J=15 Hz), 6.59 (IH, d, J=15 Hz), 4.54 (IH, m), 4.03 (IH, dd, J=4.1 and 7.9 Hz), 3.91 (IH, m), 3.69 (IH, d, J=16.7 Hz), 3.66 (IH, d, J=16.7 Hz), 3.56 (IH, dd, J=3.4 and 10.3 Hz), 3.45 (IH, dd, J=7.0 and 9.7 Hz), 3.04 (IH, dd, J=4.2 and 15.1 Hz), 3.00 (IH, m), 2.94- 2.85 (IH, m), 2.89 (3H, s), 2.80 (IH, m), 2.30 (IH, m), 2.09 (IH, m), 1.50 (IH, m), 1.43 (IH, m), 1.07 (IH, m), 0.83 (3H, t, J=6.4 Hz) and 0.75 (3H, d, J=6.7 Hz) ppm. Anal. Calcd for C36H44N4O7S-2.10 TFA-0.90 H2O: C, 51.78; H,5.18; N, 6.01. Found: C, 51.78; H, 5.17; N, 6.42. FAB HRMS exact mass calcd for C36H45N4O7S 677.300897 (MH+), found 677.299827. EXAMPLE 16 Preparation of 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylethyl)amino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine methyl ester bis trifluoroacetate Step A: Preparation of 2(S)-[2(S)-t-butoxycarbonylamino-3(S)- methyl]-pentyloxy-3-phenylpropionyl-methionine methyl ester The title compound was prepared in the same fashion as that described in Example 14 , Step F , using methionine methyl ester in place of methionine sulfone methyl ester. NMR (CD3OD) δ 0.78 (3H, d, J=6 Hz), 0.89 (3H, t, J=6 Hz). 1.1 1 (IH, m), 1.40-1.60 (2H, m), 1.47 (9H, s), 1.90-2.10 (2H,m), 2.06 (3H, s), 2.20-2.40 (2H, m), 2.90 (IH, dd, J=14.7 and 5.0 Hz), 3.05 (H,dd, J=14.5 and 3.0 Hz), 3.38 (IH, dd, J=8.6 and 7.0 Hz), 3.50-3.60 (2H, m), 3.71 (3H, s), 3.97 (IH, dd, J=7.5 and 4.0 Hz), 4.60 (IH, m), 6.60 (IH, d, J=10 Hz), 7.24 (5H, m). Step B: Preparation of 2(S)-[2(S)-amino-3(S)-methyl]-pentyloxy-3- phenylpropionyl -methionine methyl ester hydrochloride The product of Step A was converted to the title compound using the method of Example 14, Step G. iH NMR (CD3OD) δ 0.84 (3H, d, J=6 Hz), 0.93 (3H, t, J=6 Hz), 1.20 (lH, m), 1.45-1.60 (lH, m), 1.70 (lH, m), 1.80-2.20 (2H, m) 2.08 (3H, s), 2.50-2.30 (2H, m), 2.98 (IH, dd, J=14.7 and 5 Hz), 3.11 (IH, dd, J=14.5 and 3.0 Hz), 3.20-3.30 (IH, m), 3.57 (IH, m), 3.70 (IH, m), 3.73 (3H, s), 4.12 (H, dd, J=8.6 and 6.0 Hz), 4.60 (IH, m), 7.30 (5H, m). Step C: Preparation of 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-l H- imidazol-5-ylethyl)amino-3(S)-methyl]pentyloxy-3- phenylpropionyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 13, Step C, but substituting l-(2-naphthylmethyl)- lH-imidazol-5-ylacetaldehyde (30) and 2(S)-[2(S)-amino-3(S)-methyl]pentyloxy-3-phenylpropionyl- methionine methyl ester hydrochloride, the title compound was obtained. !H NMR (CD3OD, 400 MHz) δ 8.95 (IH, s), 7.96 (IH, d, J=8.5 Hz), 7.89 (2H, m), 7.79 (IH, s), 7.55 (2H, m), 7.47 (IH, s), 7.38 (IH, d, 8.4 Hz), 7.21 (4H, m), 7.15 (IH, m), 5.65 (2H, s, 4.63 (IH, dd, J=4.4 and 19.5 Hz), 4.15 (IH, dd, J=4.3 and 18.7 Hz), 3.67 (3H, s), 3.57 (2H, m), 3.43-3.15 (2H, m), 3.11-3.00 (4H, m), 2.88 (IH, dd, J=9 and 14.4 Hz), 2.51 (IH, m), 2.40 (IH, m), 2.10 (IH, m), 2.03 (3H, s), 1.95 (IH, m), 1.68 (IH, m), 1.35 (IH, m), 1.09 (IH, m), 0.86 (3H, t, J=7.2 Hz) and 0.74 (3H, d, J=6.9 Hz) ppm. Anal. Calcd for C37H48N404S-2.45 TFA: C, 54.45; H,5.50; N, 6.06. Found: C, 54.37; H, 5.51; N, 6.15. FAB HRMS exact mass calcd for C37H49N4O4S 645.34745 (MH+), found 645.34518. EX AMPLE 17 Preparation of 2(S)-[N-2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5- ylethyl)amino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine bis trifluoroacetate Following the procedure described in Example 2, Step D, but substituting the methyl ester from Example 16 provided the title compound. iH NMR (CD3OD, 400 MHz) δ 8.89 (IH, s), 7.95 (IH, d, J=8.5 Hz), 7.93-7.84 (2H, m), 7.77 (IH, s), 7.58-7.51 (2H, m), 7.45 (IH, s), 7.37 (I H, dd, J=1.7 and 8.3 Hz), 7.26-7.17 (4H, m), 7.15 (IH, m), 5.65 (2H, s), 4.59 (IH, dd, J=4.5 and 9.4 Hz), 4.14 (IH, dd, J=3.8 and 8.9 Hz), 3.56 (2H, d, J=3.8 Hz), 3.37-2.96 (6H, m), 2.88 (IH, dd, J=8.8 and 14.2 Hz), 2.52 (IH, m), 2.41 (IH, m), 2.16 (IH, m), 2.03 (3H, s), 1.97 (IH, m), 1.66 (IH, m), 1.32 (IH, m), 1.08 (IH, m), 0.85 (3H, t, J=7.1 Hz) and 0.74 (3H, d, J=7.1 Hz) ppm. Anal. Calcd for C36H46N404S-2.95 TFA-1.00 H2O: C, 51.08; H.5.21 ; N, 5.69. Found: C, 51.07; H, 5.22; N, 5.83. FAB MS calcd for C36H47N4O4S, 631 (MH+), found 631. EXAMPLE 18 Preparation of N-[2(S)-(l-methyl-imidazol-4-yl acetyl)amino-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester trifluoroacetate salt 1 -Methyl-4-imidazole acetic acid (0.070 g, 0.395 mmol), dissolved in DMF (5 mL), was treated with HOBT (0.053 g, 0.040 mmol), EDC (0.075 g, 0.395 mmol), and N-[2(S)-amino-3- methylpentyl)-N-(l-naphthylmethyl)-glycyl-methionine methyl ester hydrochloride (10, 0.175 g, 0.395 mmol). The pH was adjusted to 7.5 with Et3N (0.055 mL, 0.395 mmol) and the mixture was stirred at ambient temperature for 72 h. The mixture was concentrated and the residue was partitioned between EtOAc (30 mL) and saturated NaHCθ3 solution (25 mL). The aqueous layer was extracted with EtOAc (2x20 mL). The combined organic layer was washed with brine (1x25 mL), dried (Na2Sθ4), and evaporated in vacuo to give a crude product which was purified by chromatography (silica gel, eluting with 99:1 to 97:3 CH2θ2:MeOH) to give the amine. This material was converted to the trifluroracetate salt by dissolving in 0.1% TFA in H2θ and lyophilization to give the title compound. *H NMR (CD3OD) δ 8.72 (IH, s), 8.30- 8.20 (IH, m), 8.00-7.90 (2H, m), 7.45-7.70 (4H, m), 7.34 (IH, s), 4.80- 4.65 (IH, m), 4.60-4.40 (2H, m ), 4.20-4.10 (IH, m ), 3.86 (3H, s ), 3.70 (3H, s ), 3.85-3.50 (4H, m ), 3.40-3.30 (IH, m), 3.20-3.05 (IH, m), 2.40- 2.20 (2H, m), 2.00 (3H, s ), 2.00-1.90 (IH, m), 1.82-1.65(1H, m), 1.65- 1.52 (IH, m), 1.50-1.35 (IH, m), 1.25-1.07 (IH, m), 1.00-0.85 (6H, m). Anal. Calcd for C31H43N504S-3 TFA: C, 48.10; H, 5.02; N, 7.58. Found: C, 48.36; H, 5.30; N, 7.77. EXAMPLE 19 Preparation of N-[2(S)-(1 -methyl- lH-imidazoleacetyl) amino -3(S)- methylpentyll-N-( 1 -naphthylmethvD-glvcyl-methionine N-[2(S)-(1 -Methyl-4-imidazoleacetyl) amino-3(S)- methylpenty l]-N-( 1 -naphthylmethyl)-glycyl-methionine methyl ester (prepared in Example 18, 0.081 g, 0.139 mmol) was dissolved in MeOH (5 ml), cooled to 0°C, and IN NaOH (0.557 ml, 0.557 mmol) was added. The mixture was stirred at ambient temperature for 4 h and evaporated in vacuo. The resulting residue was dissolved in H2O (5 ml) and neutralized with IN HCI (0.557 ml, 0.557 mmol). The aqueous layer was washed with EtOAc (3x10 ml). The organic layers were combined, dried ( Na2S04), and evaporated in vacuo to give a cmde product. Purification by preparative HPLC (Vydac column eluting with acetonitrile/0.1 % TFA in H2O gradient) and lyophilization gave the title compound. iH NMR (CD3OD) δ 8.72 (IH, s), 8.31-8.23 (IH, m), 8.02-7.90 (2H, m), 7.70- 7.45 (4H, m), 7.35 (IH, s), 4.93-4.74 (IH, m), 4.58 (IH, d, J=13 Hz), 4.45-4.36 (IH, m), 4.20-4.10 (IH, m), 3.89 (3H, s), 3.86-3.52 (4H, m), 3.45-3.30 (IH, m), 3.22-3.09 (IH, m), 2.45-2.20 (2H, m), 2.00 (3H, s), 2.10-1.92 (IH, m), 1.83-1.68 (IH, m), 1.68-1.52 (IH, m), 1.52-1.37 (IH, m), 1.26-1.08 (IH, m), 1.00-0.85 (6H, m). Anal. Calcd for C3θH4lN5θ4S-2.75 CF3CO2H: C, 48.38; H, 5.00; N, 7.95. Found: C, 48.53; H, 5.05; N, 8.11. EXAMPLE 20 Preparation of N-[2(S)-l-(2-naphthylmethyl)-lH-imidazol-5- ylacetyl]amino-3(S)-me ylpentyl]-N-(cyclopropylmethyl)- lycylmethionine methyl ester bis trifluoroacetate salt Step A: Preparation of N-[2(S)-t-Butoxycarbonylamino)-3- methylpentyll-N-(cvclopropylmethyl)glvcine methyl ester N-[2(S)-t-Butoxycarbonylamino)-3(S)-methylpentyl]glycine methyl ester (6, 287.8 mg, 0.9980 mmol) was dissolved in 1,2-dichloro- ethane (7.0 ml). 4A Molecular sieves (207 mg), cyclopropane- carboxaldehyde (75 ml, 1.0 mmol), and sodium triacetoxyborohydride (1.075 g, 5.072 mmol) were added. The mixture was stirred under argon at ambient temperature for 16 h and filtered. The filtrate was diluted with EtOAc (50 mL) and washed with saturated aq NaHCθ3 (2 x 25 ml) and saturated aq NaCl (25 mL). The organic layer was dried (Na2Sθ4) and evaporated in vacuo. The cmde product was purified by chromatography (silica gel, 1 : 19 to 1:9 EtOAc/CH2Cl2) to give the title compound. !H NMR (CDCI3, 400 MHz): δ 4.85 (IH, br s), 3.69 (3H, s), 3.64-3.54 (IH, m), 3.70 (IH, d, J = 18 Hz), 3.30 (IH, d, J = 18 Hz), 2.74 (IH, dd, J = 14 and 5 Hz), 2.57-2.42 (3H, m), 1.80-1.68 (IH, m), 1.50-1.36 (IH, m), 1.44 (9H, s), 1.15-1.02 (IH, m), 0.91 (3H, t, J=7 Hz), 0.86 (3H, d, J=7 Hz), 0.86-0.76 (IH, m), 0.54-0.43 (2H, m), 0.09 (2H, d, J=5 Hz). Step B: Preparation of N-[2(S)-t-Butoxycarbonylamino)-3- methylpentyll-N-(cvclopropylmethyl)glvcine N-[2(S)-t-Butoxycarbonylamino)-3-methylpentyl]-N- (cyclopropylmethyl)glycine methyl ester (268 mg, 0.783 mmol) was dissolved in MeOH (40 ml). After cooling to 0°C under argon, IN aq LiOH (1.0 ml, 1.0 mmol) was added. After stirring at ambient temperature for 18 h, additional IN aq LiOH (1.0 ml, 1.0 mmol) was added. After stirring at ambient temperature for 6 h, additional IN aq LiOH (1.0 ml, 1.0 mmol) was added. After stirring for 18 h at ambient temperature, 1 N aq HCI (4.0 mL, 4 mmol) was added and the reaction was evaporated in vacuo. The resulting residue was dissolved in H2O (10 ml) and acidified with IN aq HCI to pH = 2. Residual methanol was evaporated in vacuo and the remaining aqueous material lyophilized to give the title compound. J H NMR (CD3OD, 400 MHz): δ 3.86-3.76 (2H, m), 3.62 (IH, d, J = 15 Hz), 3.47 (IH, br d), 3.28-3.14 (2H, m), 3.12-3.03 (IH, m), 1.64-1.43 (2H, m), 1.47 (9H, s), 1.26-1.10 (2H, m), 0.98-0.90 (6H, m), 0.80-0.68 (2H, m), 0.51-0.41 (2H, m). Step C: Preparation of N-[2(S)-t-Butoxycarbonylamino)-3- methy lpenty 1] -N-(cyclopropy Imethy 1 )gly cy lmethi onine methyl ester The title compound was prepared in the same fashion as that described in Example 1 , Step G , but using the compound described in Step B. iH NMR (CDCI3, 400 MHz): δ 8.02 (IH, br d), 4.78-4.68 (IH, m), 4.67 (IH, td, J = 9 and 6 Hz), 3.75 (3H, s), 3.70-3.60 (IH, m), 3.31 (IH, d, J = 17Hz), 3.18 (IH, d, J = 17 Hz), 2.67 (IH, dd, J = 9 and 4 Hz), 2.54 (2H, t, J = 8 Hz), 2.54-2.44 (2H, m), 2.43-2.35 (IH, m), 2.30-2.20 (IH, m), 2.16- 2.06 (IH, m), 2.10 (3H, s), 1.63-1.52 (IH, m), 1.50-1.40 (IH, m), 1.44 (9H, s), 1.17-1.05 (IH, m), 0.93 (3H, d, J = 8 Hz), 0.91 (3H, t, J = 8 Hz), 0.90-0.80 (IH, m), 0.56-0.46 (2H, m), 0.15 (2H, d, J = 6 Hz). Step D: Preparation of N-[2(S)- Amino-3-methylpentyl)-N- (cyclopropylmethyl)glycylmethionine methyl ester hydrochloride N- [2(S)-t-Butoxycarbonylamino)-3 -methy lpenty 1] -N- (cyclopropylmethyl)-glycylmethionine methyl ester (22.8 mg, 0.0481 mmol) was dissolved in EtOAc (1.5 mL) and cooled to 0°C. HCI was bubbled through the mixture until saturated. After 30 min, the mixture was evaporated in vacuo to give the title compound. iH NMR (CD3OD, 400 MHz): δ 4.68 (IH, dd, J = 9 and 5 Hz), 4.28- 4.00 (2H, m), 3.74 (3H, s), 3.70-3.45 (2H, m), 3.40-3.00 (3H, m), 2.67- 2.51 (2H, m), 2.23-1.95 (2H, m), 2.10 (3H, br s), 1.87-1.86 (IH, m), 1.60- 1.49 (IH, ), 1.34-1.21 (IH, m), 1.20-1.10 (IH, m), 1.03 (3H, d, J = 7 Hz), 1.01 (3H, t, J = 7 Hz), 0.82-0.72 (2H, m), 0.50-0.40 (2H, m). Step E: Preparation of N-[(2S)-l-(2-naphthylmethyl)-lH-imidazol- 5-ylacetyl]amino-(3S)-me ylpentyl]-N-cyclopropylmethyl)- glycylmethionine methyl ester bis trifluoroacetate salt The title compound was prepared in the same fashion as that described in Example 1 , Step I , but using the compound prepared in Step D. *H NMR (CD3OD, 400 MHz): δ 8.93 (IH, s), 7.95 (IH, d, J = 9 Hz), 7.93-7.85 (2H, m), 7.80 (IH, s), 7.60-7.53 (3H, m), 7.42 (IH, dd, J = 9 and 2 Hz), 5.68 (2H, s), 4.69-4.45 (IH, m), 4.30-3.90 (3H, m), 3.90-3.80 (2H, m), 3.69 (3H, s), 3.60-3.45 (IH, m), 3.40-3.14 (3H, m), 2.60-2.40 (2H, m), 2.15-2.05 (IH, m), 2.03 (3H, s), 2.00-1.85 (IH, m), 1.60-1.52 (lH, m), 1.50-1.40 (lH, m), 1.25-1.15 (lH, m), 1.12-1.05 (lH, m), 0.98- 0.90 (6H, m), 0.80-0.68 (2H, m), 0.50-0.40 (2H, m). FAB HRMS exact mass calcd for C34H48N5O4S: 622.342702 (MH+); found 622.343884. EXAMPLE 21 Preparation of N-[(2S)-l-(2-naphthylmethyl)-lH-imidazol-5- ylacetyl]amino-(3S)-methylpentyl]-N-(cyclopropylmethyl)- lvcylmethionine bis trifluoroacetate salt N-[(2S)-N-(2-Napthylmethyl)lH-imidazol-5- ylacetyl]amino-(3S)-methylpentyl]-N-(cyclopropylmethyl)- glycylmethionine methyl ester (19.8 mg, 0.0319 mmol) was dissolved in MeOH (0.60 ml), cooled to 0°C under argon, and treated with 1.0 N aq LiOH (38 ml, 0.038 mmol). After stirring at ambient temperature for 16 h, the reaction was diluted with MeOH (1.5 ml) and purified by preparative HPLC (chromatography method A) to give the title compound as its bis trifluoroacetate salt after lyophilization. *H NMR (CD3OD, 400 MHz): δ 8.95 (IH, s), 7.95 (IH, d, J = 9 Hz), 7.94-7.85 (2H, m), 7.82 (IH, s), 7.62-7.52 (3H, m), 7.44 (IH, dd, J = 9 and 1 Hz), 5.60 (2H, s), 4.65-4.50 (IH, m), 4.23-4.05 (2H, m), 4.01-3.93 (IH, m), 3.89 (IH, d, J = 19 Hz), 3.82 (IH, d, J = 19 Hz), 3.52 (IH, d, J = 14 Hz), 3.30-3.05 (3H, m), 2.61-2.40 (2H, m), 2.20-2.10 (IH, m), 2.05 (3H, s), 2.00-1.89 (lH, m), 1.62-1.52 (lH, m), 1.50-1.40 (lH, m), 1.25-1.04 (2H, m), 0.97 (3H, d, J = 7 Hz), 0.92 (3H, t, J = 7 Hz), 0.79-0.65 (2H, m), 0.50-0.40 (2H, m). Anal. Calcd for C33H45N5O4S-2.70 TFA-0.45 H2O: C, 49.93; H, 5.30; N, 7.58. Found: C, 49.90; H, 5.29; N, 7.92. FAB HRMS exact mass calcd for C33H46N5O4S: 608.327052 (MH+); found 608.326603. EXAMPLE 22 Preparation of N-[2(S)-[(5(R,S)-Methylpyroglutamyl)amino]-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycylmethionine methyl ester trifluoroacetate salt-diastereomers A (31) and B (32) N-[2(S)-amino-3-methylpentyl)-N-(l -naphthylmethyl)- glycyl-methionine methyl ester hydrochloride (10, 186.1 mg, 0.349 mmol) was dissolved in methylene chloride (3 mL). DL-2-Methyl-5- pyrrolidone-2-carboxylic acid (K. Pfister IH, W. J. Leanza, J. P. Conbere, H. J. Becker, A. R. Matzuk, and E. F. Rogers, J. Am. Chem. Soc, 77:697- 700 (1955), 50.2 mg, 0.351 mmol) was added followed by triethylamine (270 mL, 1.94 mmol). The mixture was cooled to 0°C under argon and treated with bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-C1, 133.3 mg. 0.5236 mmol). The reaction was stirred for 18 h at ambient temperature, diluted with EtOAc (20 mL), washed with saturated aq NaHC03 (20 mL), saturated aq NaCl (20 mL), dried (Na2S04) and evaporated in vacuo to give the cmde product as a mixture of diastereomers. Purification by chromatography (silica gel, 1:40 MeOH/CH2θ2) gave the two diastereomeric products as an inseparable mixture. Separation of the diastereomers was accomplished through prep plate chromatographies (silica gel, 3-5% MeOH/CH2Cl2) to give the high Rf diastereomer (31) and the low Rf diastereomer (32) as colorless residues. Final purification of each diastereomer was accomplished by chromatography method A. Compounds 31 and 32 were obtained as the trifluoroacetate salts by lyophilization of appropriate column fractions. 31: lH NMR (CD3θD, 400 MHz): δ 8.25-8.17 (IH, m), 7.95-7.82 (2H, m), 7.68-7.40 (4H, m), 5.10-2.80 (6H, m), 4.50-4.30 (IH, m), 4.10-3.95 (IH, m), 3.65 (3H, s), 2.60-0.90 (17H, m), 0.83 (3H, d, J = 7 Hz), 0.78 (3H, t, J = 8 Hz). Anal. Calcd for C3lH44N4θ5S*1.10 TFA-0.10 H2θ: C, 56.01 ; H, 6.41 ; N, 7.87. Found: C, 56.02; H, 6.29; N, 8.04. FAB HRMS exact mass calcd for C31H45N4O5S: 585.311068 (MH+); found 585.311 153. 32: iH NMR (CD3OD, 400 MHz): δ 8.25-8.15 (IH, m), 7.95-7.81 (2H, m), 7.65-7.38 (4H, m), 5.00-2.80 (6H, m), 4.42-4.28 (IH, m), 4.05-3.95 (IH, m), 3.63 (3H, s), 2.70-1.00 (17H, m), 0.85 (3H, br d, J = 7 Hz), 0.80 (3H, br t, J = 7 Hz). Anal. Calcd for C31 H44N405S- 1.05 TFA-0.20 H20: C, 56.14; H, 6.47; N, 7.91. Found: C, 56.17; H, 6.47; N, 8.12. FAB HRMS exact mass calcd for C31H45N4O5S: 585.311068 (MH+); found 585.311694. EXAMPLE 23 Preparation of N-[2(S)-[(5(R,S)-methyl-pyroglutamyl)amino]-3(S)- methylpentyl]-N-(l -naphthy lmethyl)-glycylmethionine trifluoroacetate salt. N-[2(S)-[(5(R,S)-Methyl-pyroglutamyl)amino]-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester (31, 32.3 mg, 0.0552 mmol) was dissolved in MeOH (1.5 mL) under argon and treated with 1.0 N aq LiOH (66 μL, 0.066 mmol). The reaction was stirred at ambient temperature for 18 h, treated with glacial acetic acid (2 drops), and purified by chromatography method A to give, after lyophilization, the title compound as a 2: 1 mixture of diastereomers as their trifluoroacetate salts. *H NMR (CD3OD, 400 MHz): δ 8.29 (IH, d, J = 8 Hz), 8.00-7.89 (2H, m), 7.78-7.45 (4H, m), 5.00-2.80 (8H, m), 2.60-1.00 (17H, m), 0.96-0.84 (6H, m). Anal. Calcd for C30H42N4O5S-1.25 TFA-0.20 H2O: C, 54.45; H, 6.14; N, 7.82. Found: C, 54.46; H, 6.14; N, 7.91. FAB HRMS exact mass calcd for C30H43N4O5S: 571.295418 (MH+); found 571.295373. EXAMPLE 24 Preparation of N-[2(S)-[(5(R,S)-methylpyroglutamyl)amino]-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)-glycylmethionine trifluoroacetate salt Following the procedure described in Example 23, but substituting the methyl ester 32 from Example 22, the title compound was prepared. iH NMR (CD3OD, 400 MHz): δ 8.36-8.26 (IH, m), 7.97 (2H, br d, J = 8 Hz), 7.80-7.44 (4H, m), 5.00-3.00 (8H, m), 2.60-1.10 (17H, m), 0.99- 0.84 (6H, m). Anal. Calcd for C30H42N4O5S-1.40 TFA-0.15 H2O: C, 53.74; H, 6.01 ; N. 7.64. Found: C, 53.73; H, 5.99; N, 7.74. FAB HRMS exact mass calcd for C30H43N4O5S: 571.295418 (MH+); found 571.296351. EXAMPLE 25 Preparation of N-[2(S)-((N-methylpyroglutamyl)amino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester trifluoroacetate salt N-methylpyroglutamate [E. Hardegger and H. Ott, Helv. Chim Acta, 38:312 (1955), 51 mg, 0.35 mmol)], dissolved in DMF (2.5 ml), was treated with HOBT (48 mg, 0.35 mmol), EDC (81 mg, 0.42 mmol), N-[2(S)-amino-3(S)-methylpentyl)-N-(l -naphthylmethyl)glycyl- methionine methyl ester hydrochloride (10, 150 mg, 0.28 mmol), and triethylamine (0.079 ml, 0.56 mmol). The mixture was stirred at room temperature for 24 hours. The mixture was partitioned between ethyl acetate and 10% citric acid solution and the organic phase was washed three times with saturated NaHC03, brine, and dried (MgSθ4). The solution was filtered through celite and evaporated in vacuo . The crude product was chromatographed (5% MeOH in EtOAc) and further purified by preparative HPLC (Waters PrepPak C-18 eluting with CH3CN/0.1 % TFA in H2θ) to give, after lyophilization, the title compound. -H NMR (CD3OD) δ 8.35(lH,d), 8.0(2H,m), 7.7(4H,m), 5.1(lH,m), 4.75(lH,m), 4.55(lH,m), 4.05(4H,m), 3.75(3H,s), 3.60(lH,m), 3.20(lH,m), 2.70(3H,s), 2.30(6H,m), 2.00(4H,m), 1.85(lH,m), 1.65(lH,m), 1.45(lH,m), 1.25(lH,m), 0.95(6H,m). FAB MS calcd for C31H45N4O5S 585 (MH+), found 585. Anal. Calcd for C31H44N4O5S-1.35TFA-1.60H2O: C, 52.73; H,6.38; N, 7.30. Found: C, 52.75; H, 6.00; N, 7.70 EXAMPLE 26 Preparation of N-[2(S)-((N-me ylpyroglutamyl)-amino)-3(S)- methylpentyll-N-( 1 -naphthylmethvD-glvcyl-methionine N-[2(S)-((N-Methylpyroglutamyl)-amino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester trifluoroacetate salt (prepared in Example 25, 112 mg, 0.19 mmol) was dissolved in methanol (5 ml) and treated with 0.76 ml of IN LiOH. The mixture was stirred for 4 hours at room temperature, then treated with 0.76 ml of IN HCI. The solvent was evacuated in vacuo. The cmde product was purified by preparative HPLC (Waters PrepPak C-18 eluting with CH3CN/O.I % TFA in H2O) to give, after lyophilization, the title compound. ΪH NMR (CD3OD) δ 8.35 (lH,d), 8.00 (2H,m), 7.65 (4H,m), 5.10 (lH,m), 4.75 (lH,m), 4.50 (lH,m), 4.05 (4H,m), 3.60 (lH,m), 3.25 (lH,m), 2.70 (3H,s), 2.30 (6H,m), 2.05 (3H,s), 1.85 (2H,m), 1.60 (lH,m), 1.45 (lH,m), 1.20 (lH,m), 0.95 (6H,m). FAB MS calcd for C30H43N4O5S: 571 (MH+), found 571. Anal. Calcd for C30H42N4O5S-1.60TFA-0.55H2O: C, 52.25; H, 5.90; N, 7.34. Found: C, 52.27; H, 5.92; N, 7.71. EXAMPLE 27 Preparation of N-[2(S)-(N-formylprolylamino)-3(S)-methylpentyl]-N-(l- naphthylmethvD-glvcyl-methionine methyl ester trifluoroacetate salt N-formyl-L-proline [T. Sawayama, et al, Chem. Pharm. Bull, 38 (2), 529-531 (1990), 44.3 mg, 0.31 mmol], dissolved in DMF (3 ml), was treated with HOBT (46 mg, 0.34 mmol), EDC (81 mg, 0.42 mmol), N-[2(S)-amino-3-methylpentyl)-N-( 1 -naphthylmethyl)glycy 1- methionine methyl ester hydrochloride (10, 150 mg, 0.28 mmol), and triethylamine (0.079 ml, 0.56 mmol). The mixture was stirred at room temperature for 72 h, then partitioned between ethyl acetate and 10% citric acid solution. The organic extract was washed with saturated NaHC03 three times, then brine, and dried (MgS04). After filtration through celite and evaporation of solvent in vacuo., the cmde product was purified by preparative HPLC (Waters PrepPak C-18 eluting with CH3CN/0.1 %TFA in H2θ) to give, after lyophilization, the title compound. J H NMR (CD3OD) 8.35 (lH,m), 8.20 (lH,s), 8.00 (2H,m), 7.65 (4H,m), 5.10 (lH,m), 4.65 (2H,m), 4.10 (4H,m), 3.75 (3H,s), 3.60 (3H,m), 3.10 (lH,m), 2.40 (2H,m), 1.90 (8H,m), 1.55 (3H,m), 1.20 (lH,m), 0.90 (6H,m). FAB MS calcd for C31H45N4O5S 585 (MH+), found 571. Anal. Calcd for C31H44N4O5S-1.40TFA-0.20H2O: C, 54.28; H, 6.1 1 ; N, 7.47. Found: C, 54.25; H, 6.16; N, 7.69. EXAMPLE 28 Preparation of N-[2(S)-(N-formylprolylamino)-3(S)-methylpentyl]-N-( 1 - naphthylmethyl)- ive yl-methionine The procedure described in Example 26, substituting the methyl ester prepared in Example 27 was used to obtain the title compound. FAB MS m/z 571 (M+l). Anal. Calcd for C30H42N4θ5Sl-1.75 TFA: C, 52.24; H, 5.72; N, 7.27. Found: C, 52.19; H, 5.82; N, 7.61. EXAMPLE 29 Preparation of N-[2(S)-(N'-(4-nitrobenzyl)-pyroglutamyl)-amino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester hydrochloride saltO Step A: Preparation of (S)-N-(4-nitrobenzyl)pyroglutamic acid methyl ester (S)-Pyroglutamic acid methyl ester (0.200 g, 1.40 mmol) was dissolved in dry THF (5 ml) and NaH (0.061 g, 1.5 mmol) was added. After gas evolution ceased, 4-nitrobenzyl bromide (0.332 g, 1.54 mmol) was added and the mixture stirred for 1 h. The reaction was quenched with saturated NaHCθ3 solution (40 mL) and extracted with EtOAc (2 x 50 ml). The organic layers were washed with water, brine, dried (MgSθ4), filtered, and concentrated to give the title compoundas a solid. iH NMR (CDCI3) δ 8.19 (d, 2H, J=8.6 Hz), 7.40 (d, 2H, J=8.6 Hz), 5.29 (d, IH, J=15 Hz), 4.19 (d, IH, J=15 Hz), 4.02 (dd, IH, J=3,9 Hz), 3.79 (s, 3H), 2.54-2.67 (m, IH), 2.42-2.51 (m, IH), 2.27-2.39 (m, IH), 2.11-2.21 (m, IH). Step B: Preparation of (S)-N-(4-nitrobenzyl)pyroglutamic acid (S)-N-(4-Nitrobenzyl)pyroglutamic acid methyl ester (0.365 g, 1.31 mmol) was dissolved in 10 ml MeOH, cooled to 0°C, and IN NaOH (5.2 ml, 5.2 mmol) was added. The reaction was stirred at room temperature for lh. Water (50 ml) was added and the aqueous was washed with 2 x 50 ml EtOAc. The aqueous was acidified with 1 N HCI and extracted with 3 x 40 ml EtOAc. The organic layers were dried (MgS04), filtered, and concentrated to give the title compound as a solid. lH NMR (d6-DMSO) δ 8.19 (d, 2H, J=8.7 Hz), 7.51 (d, 2H, J=8.6 Hz), 4.86 (d, IH, J=16 Hz), 4.19 (d, IH, J=16 Hz), 4.02-4.10 (m, IH), 3.30 (br s, IH), 2.29-2.41 (m, 3H), 1.96-2.05 (m, IH). 5 Step C: Preparation of N-[2(S)-((4- Nitrobenzyl)pyroglutamyl)amino)-3(S)-methylpentyl]-N-( 1 - naphthylmethyP-glycyl-methionine methyl ester hydrochloride salt (S)-N-(4-Nitrobenzyl)pyroglutamic acid (0.95 g, 0.36 l o mmol), N-[2(S)-amino-3-methylpentyl)-N-( 1 -naphthylmethyl)-glycyl- methionine methyl ester hydrochloride (10, 0.160 g, 0.300 mmol) and diisopropylethylamine (0.261 mL, 1.50 mmol) were dissolved in DMF (3 mL). BOP-C1 (0.137 g, 0.539 mmol) was added and the mixture was stirred at ambient temperature for 24 h. The mixture was concentrated 15 and the residue was partitioned between EtOAc (80 mL) and saturated NaHC03 solution (25 mL). The aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was washed with brine (25 mL), dried (MgSθ4), filtered, and concentrated to give a cmde product which was purified by chromatography (silica gel, eluting with 98:2 20 CH2Cl2:MeOH). Further purification by preparative HPLC (Waters C- 18 Prep Pak eluting with acetonitrile/0.1 % TFA in H2O gradient) gave the amine trifluoroacetate, which was converted to the hydrochloride salt by dissolving in EtOAc, bubbling HCI gas, filtering, and drying under vacuum to give the title compound. !H NMR (CD3OD) δ 8.29-8.41 (m, 25 IH), 8.17 (d, 2H, J=8 Hz), 7.92-8.08 (m, 2H), 7.64-7.76 (m, 2H), 7.48- 7.64 (m, 2H), 7.33-7.48 (m, 2H), 5.03-5.18 (m, IH), 4.59-4.72 (m, IH), 4.39-4.52 (m, IH), 3.81-4.27 (m, 4H), 3.72 (s, 3H),3.14-3.28 (m, IH), 2.50-2.73 (m, IH), 2.19-2.50 (m, 6H), 1.85-2.13 (m, 4H), 2.01 (s, 3H), 1.67-1.85 (m, IH), 1.41-1.53 (m, IH), 1.24-1.38 (m, IH), 1.02-1.19 (m, 30 IH), 0.72-0.94 (m, 6H). Anal. Calcd for C37H46N507S-1.95 HC1-0.95 H2O: C, 56.04; H, 6.34; N, 8.83. Found: C, 56.07; H, 6.28; N, 8.71. EXAMPLE 30 Preparation of N-[2(S)-((4-nitrobenzyl)pyroglutamyl)-amino)-3(S)- methy lpenty 1]-N-(1 -naphthylmethyl)-glycyl-methionine trifluoroacetate sail N-[2(S)-((4-Nitrobenzyl)pyroglutamyl)amino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester (0.050 g, 0.071 mmol) was dissolved in MeOH (1 ml), cooled to 0°, and IN NaOH (0.283 ml, 0.283 mmol) was added. The mixture was stirred at ambient temperature for lh. The mixture was neutralized with IN HCI (0.283 ml, 0.283 mmol). The aqueous layer was washed with EtOAc (3x10 ml). The organic layers were combined, dried with MgSθ4, filtered, and concentrated to give a cmde product. Preparative HPLC (Waters C-18 Prep Pak eluting with acetonitrile/0.1 % TFA in H2θ gradient) gave the pure title compound. 1 H NMR (CD3OD); δ 8.35 (d, IH, J=8 Hz), 8.17 (d, 2H, J=8 Hz), 7.94-8.04 (m, 2H), 7.70-7.77 (m, I H), 7.61 (t, IH, J=8 Hz), 7.52-7.63 (m, 2H), 7.42 (d, 2H, J=8 Hz), 4.93-5.10 (m, IH), 4.62-4.75 (m, IH), 4.43-4.56 (m, IH), 4.08-4.21 (m, IH), 3.81 - 4.21 (m, 4H), 3.45-3.61 (m, IH), 3.10-3.26 (m, 2H), 2.28-2.53 (m, 6H), 1.95-2.19 (m, 3H), 2.03 (s, 3H) 1.76-1.92 (m, IH), 1.41-1.54 (m, IH), 1.24-1.38 (m, IH), 1.03-1.17 (m, IH), 0.77-0.94 (m, 6H). Anal. Calcd for C36H44N507S-1.9 TFA-0.85 H2θ: C, 51.80; H, 5.20; N, 7.59. Found: C, 51.81 ; H, 5.36; N, 7.53. EXAMPLE 31 Preparation of N-[2(S)-((N'-benzylpyroglutamyl)amino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)-glycyl-methionine methyl ester trifluoroacetate salt Using the method of Example 29, substituting benzyl bromide for the p-nitrobenzyl bromide used therein, the title compound was obtained. Anal. Calcd for C37H48N405S-1.65 TFA: C, 57.01 ; H, 5.89; N, 6.60. Found: C, 56.96; H, 5.94; N, 6.91. EXAMPLE 32 5 Preparation of N-[2(S)-(N'-benzylpyro-glutamyl)amino)-3(S)- methy lpenty l]-N-( 1 -naphthylmethyl)-glycyl-methionine trifluoroacetate salt The product of Example 31 was converted to the title compound as described in Example 30. ! o FAB MS calcd for C36H47N4O5S 647 (MH+), found 647 Anal. Calcd for C36H46N4θ5S-1.5 TFA: C, 57.27; H, 5.85; N, 6.85. Found: C, 57.17; H, 5.94; N, 6.79. EXAMPLE 33 15 Preparation of N-[2(S)-l-(4-Fluorophenylmethyl)-lH-imidazol-5- ylacetyl)amino-3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl- methionine 20 Step A: Preparation of 1 -(4-Fluorophenylmethyl)- 1 H-imidazol-5- ylacetic acid The title compound was prepared as the hydrogen bromide salt using the procedures described in Example 3 steps B and C replacing 4-nitrobenzyl bromide with 4-fluorobenzyl bromide. iH NMR(CD3θD, 400 MHz) δ 8.89(1H, d, J=1.3Hz), 7.55(1H, s), 7.50- 25 7.30(2H, m), 7.17(2H, t, J=8.8Hz), 5.43(2H, s) and 3.82(2H, s) ppm. Step B: Preparation of N-[2(S)- 1 -(4-Fluoropheny Imethy 1)-1 H- imidazol-5-ylacetyl)amino-3(S)-methylpentyl]-N- 1 - 30 naphthylmethyl-glycyl-methionine methyl ester bis trifluoroacetate The title compound was prepared as the bis trifluoroacetate salt using the procedures described in example 2 step C using l-(4- Fluorophenylmethyl)- 1 H-imidazol-5-ylacetic acid. lH NMR(CD3θD, 400 MHz) δ 8.77(1H, s), 8.28(lH,m), 8.00- 7.80(2H,m)), 7.65-7.40(5H,m), 7.30-7.20(2H,m), 7.14(2H,t, J=8.6Hz),5.34(2H, m) 4.39(2H,m), 4.13(lH,m), 3.68(3H,s), 3.65- 3.40(4H,m), 2.95(lH,m), 2.40-2.15(2H,m), 1.97(3H,s), 1.95(lH,m), 1.70(lH,m), 1.60(lH,m), 1.43(lH,m), 1.07(lH,m), and 1.00-0.80(6H,m) ppm. FAB Mass spectrum, m/z = 676 (M+l). Anal, calc'd for C37H46N5O4S 0.45H2O, 1.65TFA; C, 55.50 H, 5.61 N, 8.03. Found: C, 55.50; H, 5.60; N, 8.23. Step C: Preparation of N-[2(S)- 1 -(4-Fluorophenylmethy 1)- 1 H- imidazol-5-ylacetyl)ammo-3(S)-methylpentyl]-N-l - naphthylmethyl-glvcyl-methionine bis trifluoroacetate. The title compound was prepared as the bis trifluoroacetate salt using the procedure described in Example 2 step D. iH NMR(CD3θD, 400 MHz) δ 8.79(1H, s), 8.30(lH,m), 8.00- 7.80(2H,m)), 7.65-7.40(5H,m), 7.30-7.20(2H,m), 7.13(2H,t, J=8.7Hz),5.35(2H, m) 4.38(2H,m), 4.13(lH,m), 3.80-3.40(4H,m), 3.10(lH,m), 2.40-2.15(2H,m), 1.97(3H,s), 1.95(lH,m), 1.70(lH,m), 1.60(lH,m), 1.43(lH,m), 1.07(lH,m), and 1.00-0.80(6H,m) ppm. FAB Mass spectrum, m/z = 662 (M+l). Anal, calc'd for C36H44N5O4S O.6OH2O, 2.30TFA; C, 52.16 H, 5.12 N, 7.49. Found: C, 52.18; H, 5.13; N, 7.76. EXAMPLE 34 Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl- methionine isopropyl ester Step A: Preparation of lH-Imidazole-4- acetic acid methyl ester hydrochloride. A solution of 1 H-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. !H 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 1 -(Triphenylmethyl)- 1 H-imidazol-4-ylacetic acid methyl ester. To a solution of the product from Step A (24.85g, 0.141 mol) in dimethyl formamide (DMF) (1 15ml) 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 (Na2S04) 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. !H NMR (CDC13, 400 MHz) δ 7.35(1 H, s), 7.31(9H, m), 7.22(6H, m), 6.76(1 H, s), 3.68(3H, s) and 3.60(2H, s) ppm. Step C: Preparation of [ 1 -(4-cyanobenzyl)- 1 H-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-toluonitrile (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 (MgSθ4) 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-yl]acetic 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 hydroxide (17.4 ml, 17.4 mmol) was stirred at RT for 18 hr. 1 M HCI (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. iH NMR(CD3θD, 400 MHz) d 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-[2(S)-(amino)-3(S)-methylpentyl]-N-( 1 - naphthylmethvPglvcine methyl ester hydrochloride. A solution of N-[2(S)-(t-Butoxycarbonylamino)-3(S)- methylpentyl]N( 1 -naphthylmethyl) glycine methyl ester from example 1 step E (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. lH NMR(CD30D 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 F: Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol- 5- yl] acetylamino)-3(S)-methylpentyl]-N-(l- naphthylmethyl) glycine methyl ester. To a solution of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid. (4.09g, 10.24 mmol), the amine hydrochloride salt from step E(5.07g, 10.24 mmol), HOOBT (1.67g, 10.24mmol), and N- methylmorpholine (2.36ml, 21.5mmol) in DMF (50ml) at 0°C, was added EDC (2.16g, 1 1.26 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. The residue was chromatographed (Siθ2, 3-4% MeOH in CH2CI2) to afford the title compound as a white solid. NMR(CX>30D, 400 MHz) δ 8.30(1 H,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(1 H,m), 3.65(3H,s), 3.40-3.20(2H,m), 2.92(1 H,dd, J=13.3 and 4.3Hz), 2.60(lH,dd, J=13.3 and 10.0Hz), 1.48(lH,m), 1.25(l H,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 spectrum, m/z = 552 (M+l). Step G: Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol- 5-yl]acetylamino)-3(S)-methylpentyl] -N-( 1 -naphthylmethyl) glycine. A solution of the methyl ester from step F (2.32g, 4.21mmol) 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 (Mg2S04), and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 20% MeOH in CH2CI2) to afford the title compound as a white solid. J H 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 H: Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H- imidazol-5-yl]acetylamino)-3(S)-methylpenty l]-N-( 1 - naphthylmethvDglvcyl-methionine isopropyl ester To a solution of the acid from step G (lOOmg, 0.186mmol) and methionine isopropyl ester hydrochloride (42.4mg,0.186mmol), HOOBT (30.4mg, 0.186mmol) and triethylamine (0.077ml, 0.56mmol) in DMF (1.0ml) was added EDC (37.5mg, 1.96mmol). 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 chromatographed (Siθ2, 5% MeOH in CH2CI2), evaporated to dryness and converted to the hydrochloride salt by treatment with aqueous HCI (0.32ml of a 1 M solution) and acetonitrile and lyophilisation, to afford the title compound as a white powder. Ϊ H NMR(CD3θD, 400 MHz) δ 9.00-8.90(lH, m), 8.38(1H, m),8.10- 7.10(1 lH,m),5.80-4.80 (4H, m), 4.60-3.30(1 lH,m), 2.60-1.70(8H,m), 1.60(lH,m), 1.42(lH,m), 1.21(6H,d, J=6.2Hz), 0.918(6H,br t, J=7.3Hz) ppm. FAB HRMS exact mass calc'd for C40H51 N6O4S 711.369251 (MH+), found 711367663. Anal, calc'd for C40H50N6O4S 0.55H2O and 2.80HC1 C, 58.38; H, 6.60 N, 10.21. Found: C, 58.40; H, 6.60; N, 10.36. EXAMPLE 35 Preparation of N-[2(S)-([1 -(4-cyanobenzyl)-lH- imidazol-5-yl]acetylamino)-3(S)-methylpentyl]-N-( 1 - naphthylmethyl) give yl-methionine sulfone methyl ester The title compound was prepared as the hydrogen chloride salt using the procedures described in Example 34 Steps H using methionine sulfone methyl ester hydrochloride. iH NMR(CD3θD, 400 MHz) δ 8.93(1H, m), 8.39(1H, m),8.20- 7.15(1 lH,m),5.50(2H,m), 5.40-3.00 (15H, m), 2.95(3H,s), 2.30(lH,m), 2.05(lH,m), 1.60(lH,m), 1.45(lH,m), 1.22(lH,m), 0.915(6H,m) ppm. FAB HRMS exact mass calc'd for C38H47N6O6S 715.327781 (MH+), found 715.327372. Anal, calc'd for C38H47N6O6S 0.35H2O and 3.25HC1 C, 54.36; H, 6.00 N, 10.01. Found: C, 54.36; H, 5.99; N, 10.21. EXAMPLE 36 Preparation of N-[2(S)-([1 -(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl- methionine sulfone A stirred solution of the methyl ester from Example 35 (23.7mg, O.033mmol) in THF(0.20ml) and 1 M lithium hydroxide (0.033ml, O.033mmol)was allowed to warm from 0°C to room temperature over 18hrs. The reaction was quenched by the addition of trifluoroacetic acid and the solvent evaporated in vacuo. The residue was purified by preparative hplc to afford the title compound after lyophilisation. ΪH NMR(CD30D, 400 MHz) δ 8.89(1H, m), 8.16(1H, m), 7.85- 7.20(1 lH,m),5.38(2H,m), 4.31(lH,m), 4.00(1 H,m), 3.60-3.30(7H,m), 3.00-2.90(3H,m), 2.81(3H,s), 2.14(lH,m), 1.94(lH,m), 1.431H,m), 1.29(lH,m), 1.04(lH,m), 0.78(6H,m) ppm. Anal. calc'd for C37H44N6O6S 0.45H2O, 2.30 TFA C, 51.45; H, 4.90 N, 8.65. Found: C, 51.44 H, 4.89; N, 8.62. FAB HRMS exact mass calc'd for C37H45N6O6S 701.312130(MH+), found 701.313179. EXAMPLE 37 Preparation of N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl-(3- acetylamino)alanine methyl ester The title compound was prepared as the hydrochloride salt using the procedures described in Example 34 Step H using (S)-N'-acetyl diaminopropionic acid methylester hydrochloride. iH NMR(CD3θD, 400 MHz) δ 8.90(1H, m), 8.38(1H, m),8.10- 7.20(1 lH,m), 5.60(2H,m), 5.20-3.00(10H,m), 3.60(3H,s), 1.92(3H,s), 1.83(lH,s), 1.57(lH,m), 1.43(lH,m), 1.19(lH,m), 0.90(6H,m) ppm. FAB HRMS exact mass calc'd for C38H46N7O5 680.356043(MH+), found 680.356735. Anal, calc'd for C38H45N7O5 0.35H2O and 3.05 HCI C, 57.24; H, 6.16 N, 12.30. Found: C, 57.26; H, 6.16; N, 12.40. EXAMPLE 38 Preparation of N-[2(S)-([1 -(4-cyanobenzy 1)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl-(3- acetylamino)alanine The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 37 iH NMR(CD3θD, 400 MHz) δ 8.82(1H, m), 8.40(1H, m), 7.70(2H,m), 7.65(2H,d, J=8.0Hz), 7.60-7.30(5H,m), 7.27(2H,d, J=8.0Hz), 5.40(2H,m), 4.32(lH,m), 4.00(lH,m), 3.70-3.10(10H,m), 1.75(3H,s), 1.48(lH,s), 1.33(lH,m), 1.08(lH,m), 0.80(6H,m) ppm. FAB HRMS exact mass calc'd for C37H44N7O5 666.340393(MH+), found 666.340627. 5 Anal, calc'd for C37H43N7O5 0.30H2O and2.35 TFA C, 53.33; H, 4.93 N, 10.44. Found: C, 53.33; H, 4.95; N, 10.22. EXAMPLE 39 λ 0 Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl-2(RS) amino-3-(2 thienvDpropionic acid methyl ester The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H using 2(RS) amino- 15 3-(2 thienyl)propionic acid methyl ester hydrochloride. iH NMR(CD30D, 400 MHz) δ 8.81(1H, m), 8.19(1H, d, J=9.0Hz), 8.00-7.80(2H,m), 7.62(2H,d, J=8.0Hz), 7.50-7.30(5H,m), 7.29(2H,d, J=8.0Hz), 7.036(lH,m), 6.718(lH,s), 6.61 (lH,m), 5.39(2H,m), 4.60(lH,m), 4.40(lH,m), 3.98(lH,m), 3.60(3H,s), 3.60-3.30(7H,m), 3.20- 20 2.95(3H,m), 1.47(lH,m), 1.32(lH,m), 1.08(lH,m), 0.85(6H,m) ppm. FAB HRMS exact mass calc'd for C40H45N6O4S 705.322301 (MH+), found 705.321444. Anal, calc'd for C40H44N6O4S 0.35H2O and 2.50TFA C, 54.25; H, 4.78 N, 8.44. Found: C, 54.27; H, 4.77; N, 8.36. 25 EXAMPLE 40 Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl]acetylamino)-3(S)-memylpentyl]-N-(l-naphthylmethyl)glycyl-2(RS)- 30 amino-3-(2 thienvDpropionic acid The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 39 FAB HRMS exact mass calc'd for C39H42N6O4S 691.306651 (MH+), found 691.306950. EXAMPLE 41 Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl-2(S) amino-4-sulfamyl-butanoic acid methyl ester The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H using 2(S) amino- 4-sulfamyl-butanoic acid methyl ester hydrochloride. iH NMR(CD3θD, 400 MHz) δ 8.87(1 H, m), 8.33(1 H, m), 8.00- 7.80(2H,m), 7.73(2H,d, J=8.2Hz), 7.70-7.40(5H,m), 7.35(2H,d, J=8.0Hz), 5.42(2H,m), 4.40(1 H,m), 4.10(lH,m), 3.70(3H,s), 3.60-3.20(7H,m), 3.00(3H,m),2.30(lH,m), 2.05(1 H,m), 1.55(lH,m), 1.40(lH,m), 1.15(1 H,m), 0.95(6H,m) ppm. FAB HRMS exact mass calc'd for C37H46N7O6S 716.323030(MH+), found 716.323766. Anal, calc'd for C37H45N7O6S 1.20H2O and 3.00TFA C, 47.84; H, 4.71 N, 9.08. Found: C, 47.84; H, 4.58; N, 9.26. EXAMPLE 42 Preparation of N-[2(S)-([1 -(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl-2(S) amino-4-sulfamyl-butanoic acid The title compound was prepared as the trifluoroacetate salt using the methyl ester prepared in Example 41. iH NMR(CD3θD, 400 MHz) δ 8.86(1 H, m), 8.26(1 H, m), 8.00- 7.80(2H,m), 7.73(2H,d, J=8.2Hz), 7.70-7.40(5H,m), 7.35(2H,d, J=8.0Hz), 5.47(2H,m), 4.42(lH,m), 4.08(lH,m), 3.60-3.20(7H,m), 3.00(3H,m), 2.30(lH,m), 2.05(lH,m), 1.57(lH,m), 1.38(lH,m), 1.15(lH,m), 0.95(6H,m) ppm. FAB HRMS exact mass calc'd for C36H44N7O6S 702.307379(MH+), found 702.308307. Anal, calc'd for C36H43N7O6S 0.40H2O and 2.65TFA C, 49.06; H, 4.63 N, 9.70. Found: C, 49.03; H, 4.63; N, 9.99. EXAMPLE 43 Preparation of N-[2(S)-([1 -(4-cyanobenzyl)- lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl-N- methyl methionine methyl ester The title compound was prepared as the trifluroacetate salt using the procedures described in Example 34 Step H using N-methyl methionine methyl ester hydrochloride. iH NMR(CD3θD, 400 MHz) δ 8.93(1H, m), 8.34(1H, m), 8.04(lH,d, J=7.7Hz), 7.98(lH,m), 7.75(3H,m), 7.60-7.20(6H,m), 5.48(2H,m), 5.06(lH,m), 4.40(lH,m), 4.10(lH,m), 3.66(3H,s), 3.80-3.20(9H,m), 2.85(3H,br s), 2.40-2.00(1 H,m),2.05(3H,s), 1.95(lH,m), 1.57(lH,m), 1.45(lH,m), 1.10(lH,m), 0.95(6H,m) ppm. FAB HRMS exact mass calc'd for C39H49N6O4S 697.353601 (MH+), found 697.353335. Anal, calc'd for C39H48N6O4S 0.45H2O and 2.95TFA C, 51.79; H, 5.02 N, 8.07. Found: C, 51.79; H, 4.99; N, 8.15. EXAMPLE 44 Preparation of N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl-N- methyl methionine The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 43. lH NMR(CD3θD, 400 MHz) δ 8.78(0.7H, m),8.76(0.3H,m), 8.24(1 H, m), 8.0- 7.00(1 lH,m), 5.37(2H,m), 5.00-3.00(10H,m), 2.85(3H,br s), 2.40-2.00(4H,m),1.93(0.9H,s), 1.90(2.1H,m), 1.50(lH,m), 1.31(lH,m), 1.08(lH,m), 0.80(6H,m) ppm. FAB HRMS exact mass calc'd for C36H47N6O4S 683.337951 (MH+), found 683.337329. 10 Anal, calc'd for C36H46N6O4S 2.84TFA C, 52.1 1; H, 4.89 N, 8.35. Found: C, 51.74; H, 5.02; N, 8.74. EXAMPLE 45 λ 5 Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-( 1 -naphthylmethyl)glycyl- homoserine lactone The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H using homoserine 20 lactone hydrochloride. ΪH NMR(CD30D, 400 MHz) δ 8.91 (1H, m), 8.30(1H, m), 8.05- 7.90(2H, m), 7.74(2H,d, J=8.4Hz),7.70(lH,d, J=6.2Hz), 7.60- 7.50(4H,m), 7.53(2H,d, 8.0Hz), 5.50(2H,m), 4.70(2H,m), 4.39(lH,dd,J=10.9 and 8.9 Hz), 4.30(lH,t, J=7.9Hz), 4.21(lH,m), 25 4.05(2H,m), 4.00-3.40(5H,m), 2.30(1 H,m), 1.90(lH,m), 1.57(lH,m), 1.43(lH,m), 1.18(lH,m), 0.98-0.90(6H,m) ppm. FAB HRMS exact mass calc'd for C36H41N6O4 621.318929(MH+), found 621.317455. Anal, calc'd for C39H48N6O4S 0.83H2O and 3.76TFA C, 49.1 1 ; H, 0 4.30 N, 7.90. Found: C, 49.11 ; H, 4.30; N, 8.35. EXAMPLE 46 Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-( 1 -naphthy Imethy l)glycyl- homoserine The title compound was prepared as the lithium salt using the procedures described in Example 36 and the lactone prepared in Example 45. FAB HRMS exact mass calc'd for C36H43N6O5 639.329494(MH+), found 639.328919. EXAMPLE 47 Preparation of N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl-proline methyl ester The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H using L- proline methyl ester hydrochloride. Ϊ H NMR(CD30D, 400 MHz) δ 8.80(1H, s), 8.38-8.28(1 H^n), 8.02(1H, d, J=8.4Hz), 7.96(1H, d, J=8.4Hz), 7.80-7.65(3H,m), 7.60- 7.30(6H,m), 5.55-5.40(2H,m), 5.00(lH,m), 4.40-4.00(3H,m),3.70(3H,m), 3.70-3.00(8H,m), 2.25-2.05(1 H,m), 2.00(2H,m), 1.95-1.50(2H,m), 1.40(lH,m), 1.17(lH,m), 1.00-0.80(6H,m)ppm. FAB HRMS exact mass calc'd for C38H45N6O4 649.350229(MH+), found 649.350481. Anal, calc'd for C38H44N6O4 1.75H20 and 3.00TFA C, 51.69; H, 4.98N, 8.22. Found: C, 51.69; H, 4.79; N, 8.58. EXAMPLE 48 Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl- proline The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 47. l H NMR(CD30D, 400 MHz) δ 8.85(0.8H, m), 8.80(0.2H,m), 8.32(1 H, d, J=8.4Hz), 8.04-7.90(2H,m), 7.80-7.64(3H,m), 7.60-7.28(6H,m),5.54- 5.36(2H,m), 4.40-4.00(2H,m), 3.85-3.00(10H,m), 2.20(1 H,m), 2.10- 1.80(3H,m), 1.57(lH,m), 1.42(lH,m), 1.17(lH,m), 0.98-0.82(6H,m) ppm. FAB HRMS exact mass calc'd for C37H43N6O4 635.334579(MH+), found 635.332994. Anal, calc'd for C37H42N6O4 O.8OH2O and 2.80TFA C, 52.83; H, 4.83N, 8.68. Found: C, 52.81; H, 4.81 ; N, 8.88. EXAMPLE 49 Preparation of N-[2(S)-([ 1 -(4-cyanobenzy 1)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl-D- proline methyl ester The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H using D- proline methyl ester hydrochloride. iH NMR(CD30D, 400 MHz) δ 8.92(0.3H, s), 8.88(0.7H,s),8.08- 7.90(2Hjn), 7.85-7.30(1 OH^n), 5.46(2H,m), 5.00-4.40(1 H,m), 4.35(lH,m), 4.10-4.00(2H,m), 3.60(3H,s), 3.80-3.20(8H,m), 2.20(lH,m), 2.00-1.80(3H,m), 1.60(lH,m), 1.45(lH,m), 1.15(lH,m), 1.00- 0.80(6H,m)ppm. FAB HRMS exact mass calc'd for C38H45N6O4 649.350229(MH+), found 649.351271. Anal, calc'd for C38H44N6O4 2.20H2O and 3.00TFA C, 51.28; H, 5.03N, 8.16. Found: C, 51.27; H, 4.71 N, 8.39. EXAMPLE 50 Preparation of N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl- proline The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 49. iH NMR(CD3θD, 400 MHz) δ 8.80-8.70(lH, m), 8.30-8.15(lH, m), 8.00-7.20(1 lH,m), 5.40(0.4H,s), 5.35(1.6H,m), 5.00-4.60(1 H,m), 4.24(lH,m), 3.97(lH,m), 3.70-3.00(10H,m), 2.20-2.00(1 H,m), 2.00- 1.60(2H,m), 1.50(lH,m), 1.34(lH,m), 1.08(lH,m), 1.90-0.70(6H,m)ppm. FAB HRMS exact mass calc'd for C37H43N6O4 635.334579(MH+), found 635.333794. Anal, calc'd for C37H42N6O4 0.50H2O and 2.55TFA C 54.1 1 H, 4.91N, 8.99. Found: C, 54.1 1 ; H, 4.93; N, 8.95. EXAMPLE 51 Preparation of N-[2(S)-([1 -(4-cyanobenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-( 1 -naphthylmethy l)glycyl-L- pipecolinic acid The title compound was prepared as the trifluroacetate salt using the procedures described in Example 34 Step H using L-pipecolinic acid . iH NMR(CD3θD, 400 MHz) δ 8.96-8.84(lH,m),8.36(lH,m), 8.10- 7.20(1 lH,m), 5.45(2H,m), 5.20-4.40(1 H,m), 4.40-4.00(3H,m), 4.00- 3.00(9H,m), 2.20(2H,m), 1.80-1.05(6H,m), 1.00-0.80(6H,m)ppm. FAB HRMS exact mass calc'd for C38H45N6O4 649.350229(MH+), found 649.352801. Anal, calc'd for C38H44N6O4 2.75TFA C, 54.29; H, 4.90N, 8.73. Found: C, 54.22; H, 4.88 N, 8.89. EXAMPLE 52 Preparation of N-[2(S)-([1 -(4-carbomethoxybenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-( 1 -naphthy Imethy l)glycyl- methionine methyl ester The title compound -as the trifluoroacetate salt- was isolated as a minor component of the reaction mixture prepared in Example 9 Step A . *H NMR(CD30D, 400 MHz) δ 8.93( lH,s),8.30(lH,m), 8.05- 7.35(9H,m), 7.31(2H,d, J=8.2Hz), 5.48(2H,m), 5.00-4.40(1 H,m), 4.39(lH,s), 4.05(lH,m), 3.90(3H,m), 4.00-3.30(7H,m), 3.67(3H,m), 3.17(lH,m), 2.20-2.10(2Hjn), 1.98(3H,s), 1.75(lH,m), 1.55(lH,m), 1.40(lH,m), 1.18(lH,m), 1.00-0.80(6H,m)ppm. Anal, calc'd for C39H49N5O6S 0.15H2O, 2.15TFA C, 53.96; H, 5.38; N, 7.27. Found: C, 53.96; H, 5.39 N, 7.59. EXAMPLE 53 Preparation of N-[2(S)-([l-(4-carbomethoxybenzyl)-lH-imidazol-5- yl]acetylamino)-3(S)-methylpentyl]-N-(l -naphthylmethyl)glycyl- methionine The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 52. iH NMR(CD3θD, 400 MHz) δ 8.80(1 H, m), 8.20(1 H, m), 8.00- 7.20(1 lH,m), 5.40(2H,m), 5.00-4.60(1 H,m), 4.32(lH,m), 4.05(lH,m), 3.80(3H,s), 3.70-3.00(7H,m), 2.40-2.00(3H,m), 1.88(3H,s), 1.75(lH,m), 1.55(lH,m), 1.30(lH,m), 1.05(lH,m), 1.00-0.65 (6H,m)ppm. Anal. calc'd for C38H47N5O6S 0.15H2O and 2.85TFA C, 50.98 H, 4.91N, 6.80. Found: C, 50.98; H, 4.89; N, 7.19. EXAMPLE 54 Preparation of l-(2-naphmylmethyl)-lH-imidazol-5-ylacetyl- isoleucinyl- phenylalaninyl-methionine methyl ester The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 34 Step H and isoleucinyl- phenylalaninyl-methionine methyl ester hydrochloride. Ϊ H NMR(CD3θD, 400 MHz) δ 8.89(1 H, s), 8.39(1 H,d, J=8.0Hz), 8.19(2H,m), 8.00-7.90(3H,m), 7.67(lH,s), 7.60-7.52(2H,m), 7.48(lH,s), 7.36(lH,d,J=8.0Hz), 7.30-7.10(5H,m), 5.56(lH,d,J=15.0Hz), 5.49(lH,dJ=15.0Hz), 4.69(lH,m), 4.52(lH,m), 4.20-4.14(lH,m), 3.54(lH,d, J=18.0Hz), 3.66(1 H,d,J=l 8.0Hz), 3.66(3H,s), 3.14(lH,dd,J=15.0 and 6.0Hz), 2.91(lH,dd, J=15.0 and 9.0Hz), 2.56- 2.16(2H,m), 2.06(lH,m), 2.04(3H,s), 1.89(lH,m), 1.73(lH,m), 1 -40( 1 H,m), 1.08( 1 H,m), 0.90-0.80(6H,m)ppm. FAB HRMS exact mass calc'd for C37H46N5O5S 672.321967(MH+), found 672.321794. Anal, calc'd for C37H45N5O5S 0.10H2O and 2.30TFA C, 57.87; H, 5.70N, 8.52. Found: C, 57.88; H, 5.61 N, 8.49. EXAMPLE 55 Preparation of 1 -(2-naphthylmethyl)- 1 H-imidazol-5-ylacetyl-isoleucinyl- phenylalaninyl-methionine The title compound was prepared as the trifluoroacetate salt using the procedures described in Example 36 and the methyl ester prepared in Example 54. lH NMR(CD3θD, 400 MHz) δ 8.80(1H, s), 8.15(lH,d, J=8.0Hz), 7.93(lH,d,J=8.0Hz), 7.89(2H,m), 7.74(lH,m), 7.58-7.52(2H,m), 7.44(1 H,s), 7.35(lH,dd, J=10.0 and 3Hz), 7.30-7.10(5H,m), 5.54(lH,d,J=15.0Hz), 5.47(lH,d, J=15.0Hz), 4.70(lH^n), 4.50(lH,m), 4.15(lH,m), 3.51(lH,d, J=17.0Hz), 3.66(lH,d,J=17.0Hz), 3.18(lH,dd,J=15.0 and 6.0Hz), 2.92(1 H,dd, J=15.0 and 9.0Hz), 2.56-2.40(2H,m), 2.10(lH,m), 2.05(3H,s), 1.92(lH,m), 1.73(lH,m), 1.40(lH,m), 1.08(lH,m), 0.90- 0.80(6H,m)ppm. FAB HRMS exact mass calc'd for C36H44N5O5S 658.305448(MH+), found 658.306317. EXAMPLE 56 In vitro inhibition of ras famesyl transferase Assays of farnesyl-protein transferase. Partially purified bovine FPTase and Ras peptides (Ras-C¥LS, Ras-C¥IM 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.SA. 56:6630-6634 (1989), respectively. Bovine FPTase was assayed in a volume of 100 μl containing 100 mM 7V-(2-hydroxy ethyl) piperazine- V'-(2-ethane sulfonic acid) (HEPES), pH 7.4, 5 mM MgCl2, 5 mM dithiothreitol (DTT), 100 mM [3H]-farnesyl diphosphate ([3H]-FPP; 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 incorporation of famesyl in the presence of the test compound when compared to the amount of incorporation in the absence of the test compound. Human FPTase was prepared as described by Omer et al, Biochemistry 52:5167-5176 (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-C¥IM were added to the reaction mixture. 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 were tested for inhibitory activity against human FPTase by the assay described above and were found to have IC50 of < 10 μM. EXAMPLE 57 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 57 :712-717, (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 serum and 400 mCi[35S]methionine (lOOO Ci/mmol). After 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. 45:294-304, (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 nonfarnesylated ras proteins are compared to determine the percent inhibition of famesyl transfer to protein. o EXAMPLE 58 In vivo growth inhibition assay To determine the biological consequences of FPTase inhibition, the effect of the compounds of the instant invention on the 5 anchorage-independent growth of Ratl cells transformed with either a v- ras, \-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. Ratl cells transformed with either v-ras, v-raf, or v-mos are o 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 serum) over a bottom agarose layer (0.6%). Both layers contain 0.1 % methanol or an appropriate concentration of the instant compound (dissolved in methanol 5 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 were seeded and comparisons are made. 0

Claims: WHAT IS CLAIMED IS: 1. A compound which inhibits Ras farnesyl- transferase having the formula I: wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, Nθ2, (Rl0)2N-C(NRl0)-, Rl0C(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lθC(O)NRl -, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl lθC(O)NRl0-; R2a and R2b 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 C1-C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or 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, (R10)2N-C(NR10)., RlOc(O)-, Rl θC(O)-, N3, -N(R lO)2, Rl lOC(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 R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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 C1 -C2O alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, Nθ2, R 10 O-, Rl lS(0) m -, R!0C(O)NR10-, CN, (R10)2N-C(NR10)-, R IO O)-, R lOθC(O)-, N3, -N(R lO)2, Rl lOC(O)NRl0- and C1-C20 alkyl, and d) Cl -Q) alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R3 and R4 are combined to form - (CH2)s - ; R^ a and R5b 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 C1-C2O alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocycle group, wherein the substituent is selected from F, Cl, Br, N(Rl°)2, Nθ2, R 10 O-, Rl lS(0)m-, R 10 C(O)NRl -, CN, (RlO)2N-C(NRl )., RIOC(O)-, RlOθC(O)-, N3, -N(Rl )2, RllOC(O)NRl -, -Sθ2N(Rl ) 2 , Rl ISO2NR O- and C1-C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; or R5a and R5b are combined to form - (CH2)s - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0) , -NC(O)-, and-N(CORl ). ; or R5a or R5b are combined with R 14 to form a ring such that X-Y is fj* 7a a) o H e) ^Y7 , or H f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C l -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C 1 -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, R!°C(O)NR10-, CN, N02, R 1°2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl0)2, or Rl lOC(O)NRl0-, and c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, Rl O-, Rl lS(0) m -, Rl°C(0)NH-, CN, H2N-C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R 1 l S(0) m -, R 10 C(O)NRl -, CN, N02, (R 10 )2N- C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl C(0)NRl -, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lθC(O)NRl0- ; R lO is independently selected from hydrogen, C1 -C6 alkyl and aryl; Rl 1 is independently selected from Cl -Cβ alkyl and aryl; Rl2 is independently selected from hydrogen and C1 -C6 alkyl; Rl4 is independently selected from hydrogen,Cl -C6 alkyl and benzyl; Rl5 is independently selected from hydrogen and C1-C6 alkyl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, O, -N(RlO)-, -C(O)-, -C(O)NRl0-, -NRIOC(O)-, -S(0) 2 N(RlO)-, -N(RlO)S(0)2- or S(0) m ; ¥ is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl ; provided that ¥ is not hydrogen if Al is S(0)m and ¥ is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0) m or a bond; W is a heterocycle; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when ¥ is hydrogen; s is 4 or 5; and t is 3, 4 or 5; o or a pharmaceutically acceptable salt thereof. 2. A prodrug of a compound of Claim 1 having the formula II: 0 wherein: R 1 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0)m- . R 10 C(O)NRl _, CN, Nθ2, 5 (Rl ) 2 N-C(NRlO)-, RlOc(0)-, Rl0θC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, R OO-, R 1 ^(O^-, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, 0 Rl C(O)-, Rl θC(O)-, N3, -N(Rl0) 2 , or R1 1OC(O)NR1 . ; R2a and R2b 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 C l -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or 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)-, RlOC(O)-, R lOθC(O)-, N3, -N(R lO)2, RH θC(O)NRl - and C1 -C2O alkyl, and d) C1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2a and R2b are combined to form - (CH2)s - . d R4 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 C1 -C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, R 10 O-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, R 1 lθC(O)NRl0- and C1-C2O alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl; or R3 and R4 are combined to form - (CH2)s - . R5a and R5b 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 C1-C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocycle group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, R 10 O-, RHS(0) m -, R!0C(O)NR10-, CN, (RlO)2N-C(NRlO)., RIOC(O)-, R lOθC(O)-, N3, -N(RlO)2, R 1 lOC(O)NRl0- , -SO2N(Rl )2, Rl lS02 RlO-and C1-C2O alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; or R5a and R5b are combined to form - (CH2)s - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0)m . -NC(O)-, and -N(COR 1 )- ; or R5a or R5b are combined with R 14 to form a ring such that R6 is a) substituted or unsubstituted C1-C8 alkyl, wherein the substituent on the alkyl is selected from: D aryl, 4) -OR 10, or X-Y is fj 7b 3 > ^ °£ R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C 1 -C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R OO-, Rl lS(0) m -. Rl0C(O)NRl0-, CN, N02, Rl°2N-C(NRlO)-, R 10 C(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0., and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RIOQ-, Rl ^(O^-, Rl0C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl l0C(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl !S(0)m-, Rl0C(O)NRl0-, CN, Nθ2, (R 10 )2N- C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(R lO)2, or Rl lOC(O)NRl0-, and c) C l -C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRl )-, R l0c(O)-, RlOθC(0)-, N3, -N(RlO)2, or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from Cl-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and -C6 alkyl; R 3 is independently selected from -C6 alkyl; Rl4 is independently selected from hydrogen,Cl-C6 alkyl and benzyl; Rl5 is independently selected from hydrogen and Cl -C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, -NRl C(O)-, -S(O)2N(Rl0)., -N(Rl0)S(O)2- or S(0) m ; ¥ is selected from: a) hydrogen, b) heterocycle, c) aιyl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl ; provided that ¥ is not hydrogen if Al is S(0)m and ¥ is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when ¥ is hydrogen; s is 4 or 5; and t is 3, 4 or 5; or a pharmaceutically acceptable salt thereof. 3. A compound which inhibits Ras farnesyl- transf erase having the formula UI: V - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - III wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, R lS(0)m-, R 10 C(O)NRl0-, CN, N02, (R10)2N-C(NR10)., RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lθC(O)NRl0-, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, R 1 ^(O)™-, Rl0C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or R 1 1QC(0)NR10-; R2a and R2b 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 C1-C2O alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, R 10 O-, Rl lS(0)m-, Rl0C(O)NRl0-, CN, (R!0)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO)2, Rl lθC(O)NRl0- and C1-C2O alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2a and R2b are combined to form - (CH2)s - . R3 and R4 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 a id which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C1-C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, R 10 O-, Rl lS(0) m -, R!0C(O)NR10-, CN, (RlO)2N-C(NRlO)-, RIOC(O)-, RlOθC(O)-, N3, -N(RlO)2, R11OC(O)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; or R3 and R4 are combined to form - (CH2)s - ; X-Y is o7a 0 b f) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C l -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, Nθ2, Rl 0 2N-C(NRlO)-, Rl C(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, 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 Rl lθC(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl l S(0) m -, Rl0C(O)NRl0-, CN, NO2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO)2, or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R lOO-, R l lS(0) m -, R 10C(0)NR10-, CN, (Rl ) 2 N-C(NRl )-, R lOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lθC(O)NRl0. ; RlO is independently selected from hydrogen, Cl -C6 alkyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl2 is independently selected from hydrogen and C1-C6 alkyl; Rl4 is independently selected from hydrogen,Cι-C6 alkyl and benzyl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(R10)-, -NR10C(O)-, -S(0)2N(RlO)-, -N(RlO)S(0)2- or S(0) m ; ¥ is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl ; provided that ¥ is not hydrogen if A 1 is S(0)m and ¥ is not hydrogen if A 1 is a bond, n is 0 and A 2 is S(0)m or a bond; W is a heterocycle; Z is independently H2 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 or 2; r is 0 to 5, provided that r is 0 when ¥ is hydrogen; and s is 4 or 5; or a pharmaceutically acceptable salt thereof. 4. A prodrug of a compound of Claim 3 of the formula I¥: - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - W - IV wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0) m -, R10C(O)NR10-, CN, N02, (R10)2N-C(NR10)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0)m-. Rl°C(O)NRl0-, CN, (R10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lOC(O)NRl0-; R2a and R2b 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 C1-C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R1 C(O)NR 1 -, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl0)2, Rl lOC(O)NRl0- and C1 -C2O alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02, Rl°0-, Rl lS(0) m -, R !0C(O)NR10., CN, (RlO)2N-C(NRlO)., R l0c(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and Ci- o alkyl, and d) Cl- ) alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R3 and R4 are combined to form - (CH2)s - . X-Y is l=_ 7b R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C l -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, R !0C(O)NR10-, CN, N02, R1°2N-C(NR10)-, RlOC(O)-, Rl θC(O)-, N3, -N(R lO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NH-, CN, H2N-C(NH)-, RlOC(O)-, Rl θC(O)-, N3, -N(RlO)2, or R lθC(0)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0)πr, Rl0c(O)NRl0-, CN, N02, (Rl°)2N- C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(R l )2, or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, (Rl ) 2 N-C(NRlO)-, R lOc(O)-, RlOθC(O)-, N3, -N(R lO)2, or Rl lθC(O)NRl0. ; R 10 is independently selected from hydrogen, C 1 -Cβ alkyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; R is independently selected from hydrogen and -C6 alkyl; Rl4 is independently selected from hydrogen,Cl-C6 alkyl and benzyl; A 1 and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(R 10)-, -NRIO O)-, -S(O)2N(Rl0)-, -N(RlO)S(0)2- or S(0) m ; ¥ is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl ; provided that ¥ is not hydrogen if Al is S(0)m and ¥ is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle; Z is independently H2 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 or 2; r is 0 to 5, provided that r is 0 when ¥ is hydrogen; and s is 4 or 5; or a pharmaceutically acceptable salt thereof. 5. The compound according to Claim 1 having the formula I I wherein: R 1 is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, R OO-, -N(Rl°)2 or alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, RlOO-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl -C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0) m -, R! C(O)NR 10-, CN, (Rl ) 2 N-C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , Rl lθC(O)NRl0- and -C20 alkyl, and c) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; and R b is selected from hydrogen and C1-Q3 alkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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 C1-C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, R 10 O-, Rl lS(0)m-, Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl OC(O)NRl0- and C1-C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; R5a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from methionine and glutamine, 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, Nθ2, Rl°0-, Rl lS(0)πr, R10C(0)NR1 -, CN, (R10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lθC(0)NRl -, -Sθ2N(Rl0) 2 , Rl lSθ2NR lO- and C1 -C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; R5b is selected from: a) hydrogen, and b) C1-C3 alkyl; or R5a or R5b are combined with Rl4 to form a ring such that X-Y is C) ^ θ) -CH 2 -CH - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C 1 -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, 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-, R1 C(O)NR1 -, CN, N02, (RlO)2N-C(NRl )., RIOC(O)-, RlOθC(O)-, -N(RlO) 2 , or R lθC(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 Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOo-, Rl lS(0) m -, R10C(O)NR1 -, CN, NO2, (RlO) 2 N-C(NR lO)-, RlOc(0)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, Rl O-, Rl lS(0)m-. Rl0C(O)NRl0-, CN, (RlO) 2 N-C(NRl )-, R lOc(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0- ; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; R 1 1 is independently selected from Cl -Cβ alkyl and aryl; Rl2 is independently selected from hydrogen and C1 -C6 alkyl; Rl4 is independently selected from hydrogen and C1 -C6 alkyl; Rl5 is independently selected from hydrogen and C1 -C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, -NRlOC(O)-, -S(O)2N(Rl0)-, -N(Rl )S(0)2- or S(0) m ; ¥ is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C l -C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that ¥ is not hydrogen if A is S(0)m and ¥ is not hydrogen if A is a bond, n is 0 and A is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 2; s is 4 or 5; and t is 3, 4 or 5; or a pharmaceutically acceptable salt thereof. 6. The compound according to Claim 2 having the formula II: (R B )r R' V - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - W - II wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, RlOO-, -N(R 1 )2 or alkenyl, c) Cl -C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, R OO-, or -N(RlO)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl-ClO alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, NO2, Rl°0-, Rl lS(0) m -, R10C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , Rl lOC(O)NRl0- and C1-C20 alkyl, and c) Cl -Cβ alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; and R2b is selected from hydrogen and C1-Q3 alkyl; or R2a and R2b are combined to form - (CH2)s - ' R3 and R4 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 C 1 -C 10 alkyl , C2-C 10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0) m -, R1°C(0)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0. and C1-C20 alkyl, and d) Cl -Q) alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; R5a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from methionine and glutamine, 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R!0C(O)NR10., CN, (RlO)2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0-, -Sθ2N(RlO) 2 , Rl ISO2NR O- and -C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R5a is selected from: a) hydrogen, and b) Cl-C3 alkyl; or R5a or R5b are combined with R 14 to form a ring such that a) substituted or unsubstituted -C alkyl, wherein the substituent on the alkyl is selected from: D aryl, 4) -OR 10, or X-Y is ι7b b) \ ^ N b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) Cl -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, 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)NR10-, CN, N02, (R10)2N-C(NR10)-, RlOc(O)-, R10OC(O , -N(RlO)2, or Rl lθC(O)NRl0-, and c) Cl-Cfe alkyl substituted by C1-C6 perfluoroalkyl, Rl°0-, Rl0C(O)NRl0-, (R10) 2 N-C(NR10)-, 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, R OO-, Rl lS(0)m-, R1°C(0)NR10-, CN, N02, (R10) 2 N-C(NR10)., R10C(O)-, RlOθC(O)-, -N(RlO)2, or RHθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C 1 -Cβ perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)m-, Rl0c(O)NRl0., CN, (R10) 2 N-C(NR10)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or R1 10C(0)NR 10- ; RlO is independently selected from hydrogen, C1-C6 alkyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and C1-C6 alkyl; Rl3 is 1 ,1-dimethylethyl; Rl4 is independently selected from hydrogen and C1-C6 alkyl; Rl is independently selected from hydrogen and Cl -Cβ alkyl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, -NRlOc(O)-, -S(O)2N(Rl0)., -N(RlO)S(0)2- or S(0) m ; ¥ is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) Cl -C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that ¥ is not hydrogen if A is S(0) m and ¥ is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 or O; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; p is 0, 1 , 2, 3 or 4; r is 0 to 2; s is 4 or 5; and t is 3, 4 or 5; or a pharmaceutically acceptable salt thereof. 7. The compound according to Claim 3 having the formula ID: III wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, RlOO-, -N(RlO)2 or alkenyl, c) C1-C6 alkyl unsubstituted or substitπtσett 'tftyl, heterocyclic, cycloalkyl, alkenyl, RlOO-, or -N(Rl0)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl-ClO alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-, R1°C(0)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, R lOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and -C20 alkyl, and c) C1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; and R2b i selected from hydrogen and Cl- , alkyl; or R2a and R2b are combined to form - (CH2)s - * R3 and R4 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m- . R1°C(0)NR10-, CN, (R 10) 2 N-C(NR10)-, RlOc(O)-, R lOθC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0- and -C20 alkyl, and d) C1-Q3 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; X-Y is R 7b b) \ X .N ? * - c) -^ y- e) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) C 1 -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and C 1 -Cβ alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl-C6 perfluoroalkyl, F, Cl, RlOO-, R 0C(O)NR10-, CN, N02, (RlO)2N-C(NRlO)-, R IOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl 10C(0)NR 10-, and c) C1-C6 alkyl substituted by Cl-Cό perfluoroalkyl, RlOo-, Rl0C(O)NRl0-, (R10)2N-C(NR10)-, RlOc(O)- RlOθC(O)-, -N(R lO)2, or R HOC(O)NR 10- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)πr. R 10 C(O)NRl0-, CN, N02, (R 10) 2 N-C(NR10)-, R 10C(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1 -C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, Rl O-, R l lS(0) m -, Rl0C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, R IOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lθC(0)NRlO- ; RlO is independently selected from hydrogen, C1 -C6 alkyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl is independently selected from hydrogen and Cl -Cβ alkyl; Rl4 is independently selected from hydrogen and -C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(R lO)-, -NRlOc(O)-, -S(0)2N(RlO)-, -N(RlO)S(0)2- or S(0) m ; ¥ is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C20 alkenyl; provided that ¥ is not hydrogen if Al is S(0)m and ¥ is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 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 or 2; r is 0 to 2; and s is 4 or 5; or a pharmaceutically acceptable salt thereof. 8. The compound according to Claim 4 having the formula I¥ : V - A 1 (CR 1 2 ) n A 2 (CR 1 2 ) n - W - IV wherein: Rl is independently selected from: a) hydrogen, b) aryl, heterocyclic, cycloalkyl, Rl°0-, -N(R 1°)2 or alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, R 1 OO-, or -N(R 10)2; R2a is selected from: a) a side chain of a naturally occurring amino acid, wherein the amino acid is selected from alanine, leucine, isoleucine and valine; b) substituted or unsubstituted Cl -ClO alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, Rl lS(0)m-. R 10 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0- and C1-C20 alkyl, and c) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; and R2b i selected from hydrogen and Cl -C6 alkyl; or R2a and R2b are combined to form - (CH2)s - ; R3 and R4 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, C2-C10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N02, Rl°0-, R 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, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 cycloalkyl; X-Y is >7a a) O e) -CH 2 -CH 2 - ; R7a is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, and e) C1-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R7b is selected from a) hydrogen, b) unsubstituted or substituted aryl, c) unsubstituted or substituted heterocyclic, d) unsubstituted or substituted cycloalkyl, e) Cl -C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, f) a carbonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl -C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl, and g) a sulfonyl group which is bonded to an unsubstituted or substituted group selected from aryl, heterocyclic, cycloalkyl and Cl-C6 alkyl substituted with hydrogen or an unsubstituted or substituted group selected from aryl, heterocyclic and cycloalkyl; wherein heterocycle is selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl; R8 is selected from: a) hydrogen, b) Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl -Cβ perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR10-, CN, N02, (R10)2N-C(NR10)., R10C(O)-, RlOθC(O)-, -N(R l0)2, or Rl lθC(O)NRl0-, and c) C1-C6 alkyl substituted by -Cό perfluoroalkyl, RlOo-, RlOC(0)NRlO-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl 10C(0)NR10- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1 -C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)πr. R 10 C(O)NRl0_, CN, NO2, (Rl0) 2 N-C(NRl0)-, Rl0c(O)-, RlOθC(O)-, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, RlOC(0)NRlO-, CN, (RlO) N-C(NRlO)-, R IOC(O)-, RlOθC(O)-, -N(RlO)2, or R 1 1OC(O)NR10. ; RlO is independently selected from hydrogen, Cj-C6 alkyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is independently selected from hydrogen and C1 -C6 alkyl; Rl4 is independently selected from hydrogen and C1-C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, -NRlOC(O)-, -S(0)2N(RlO)-, -N(Rl0)S(O)2- or S(0) m ; ¥ is selected from: a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, b) aryl, c) C1-C20 alkyl wherein from 0 to 4 non-terminal carbon atoms are replaced with a heteroatom selected from O, S, and N, and d) C2-C2O alkenyl; provided that ¥ is not hydrogen if Al is S(0) and ¥ is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m or a bond; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, piperidinyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; Z is independently H2 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 or 2; r is 0 to 2; and s is 4 or 5; or a pharmaceutically acceptable salt thereof. 9. A compound which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(Phenylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-4-ylacety l)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-( 1 -(Phenylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(1 -(Phenylmethyl)- 1 H-imidazol-5-ylacetyl)-amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(1 -(4-Nitrophenylmethyl)- 1 H-imidazol-4-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[(2S)-(l-(4-Nitrophenylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N- [2(S)-(l-(4-Nitropheny Imethy 1)-1 H-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Nitrophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthy Imethy 1-glycyl-methionine N-[2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-( 1 -( 1 -Naphthylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -( 1 -Naphthylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-Famesyl-lH-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(1 -Famesyl- 1 H-imidazol-5-ylacetyl)amino-3 (S)-methy lpenty 1] - N-1-naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-Geranyl-lH-imidazol-5-ylacetyl)amino-3(S)-methylpentyl]- N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -Geranyl- 1 H-imidazol-5-ylacetyl)amino-3 (S)-methylpentyl] - 5 N- 1 -naphthylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-4-ylacetyl)amino-3(S)- methy lpenty 1]-N-1 -naphthylmethyl-glycy 1-methionine ! o N-[2(S)-( 1 -(4-Pyridylmethyl)-l H-imidazol-4-ylacetyl)amino-3(S)- methy lpenty 1J-N-1 -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-5-ylacetyl)amino-(3S)- methylpentyl]-N-l -naphthy Imethy 1-glycyl-methionine 15 N-[2(S)-(l-(4-Pyridylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- o methy lpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-( 1 -(4-Cyanophenylmethyl)-l H-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l -naphthy Imethy 1-glycyl-methionine methyl ester 5 N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-y lacety l)amino- 3(S)-methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester 0 N-[2(S)-(l-(4-Ouinolinylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-(l-(4-Quinolinylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methy lpenty I] -N-l -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -phenylmethyl-glycyl-methionine N-[2(S)-(1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylacetyI)amino-3(S)- methylpentyl]-N-l -phenylmethyl-glycyl-methionine methyl ester N-[2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylethyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethy 1-glycyl-methionine N-[2(S)-( 1 -(2-Naphthylmethy 1)- 1 H-imidazol-5-ylethy l)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester 2(S)-[N-2(S)-(l-(2-Naphthy Imethyl)- lH-imidazol-5-ylacetyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester 2(S)-[N-2(S)-( 1 -(2-Naphthy Imethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine sulfone 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylethyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine methyl ester 2(S)-[N-2(S)-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylethyl)amino-3(S)- methyl]pentyloxy-3-phenylpropionyl-methionine N-[2(S)-(l-Methyl-lH-imidazol-4-ylacetyl)-amino-3(S)-methylpentyl]- N-(l -naphthy Imethy l)-glycyl-methionine methyl ester N- [2(S)-(1 -Methyl- lH-imidazol-4-ylacetyl)-amino -3(S)-methylpentyl]- N-( 1 -naphthy Imethy l)-glycyl-methionine N-[2(S)-N-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]amino-(3S)- methylpentyl]-N-(cyclopropylmethyl)-glycylmethionine methyl ester N-[(2S)-N-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]amino-(3S)- methylpentyl]-N-(cyclopropylmethyl)-glycylmethionine N-[2(S)-[(5(R,S)-Methylpyroglutamyl)amino]-3(S)-methylpentyl]-N-( l naphthylmethyl)-glycylmethionine methyl ester N-[2(S)-[(5(R,S)-Methylpyroglutamyl)amino]-3(S)-methylpentyl]-N-( l - naphthylmethyl)-glycylmethionine N-[2(S)-((N-Methylpyroglutamyl)amino)-3(S)-methylpentyl]-N-( 1 - naphthylmethyl)-glycyl-methionine N-[2(S)-((N-Methylpyroglutamyl)-amino)-3(S)-methylpentyl]-N-( 1 - naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N-Formylprolylamino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N-Formylprolylamino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine N-[2(S)-(N'-(4-Nitrobenzyl)pyroglutamyl)-amino)-3(S)-methylpentyl]- N-(l-naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N'-(4-Nitrobenzyl)pyroglutamyl)-amino)-3(S)-methylpentyl]- N-( 1 -naphthy Imethy l)-glycy 1-methionine N-[2(S)-((N'-Benzylpyroglutamyl)amino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine methyl ester N-[2(S)-(N'-Benzylpyroglutamyl)amino)-3(S)-methylpentyl]-N-(l- naphthylmethyl)-glycyl-methionine N-[2(S)-l-(4-Fluorophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methy lpenty I] -N- 1 -naphthylmethyl-glycy 1-methionine methyl ester N-[2(S)-l -(4-Fluorophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine N-[2(S)-([ l -(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methy lpenty l]-N-( 1 -naphthylmethyl)glycyl-methionine isopropyl ester N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine sulfone methyl ester N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine sulfone N-[2(S)-([ l -(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methy lpentyl]-N-( 1 -naphthylmethyl)glycyl-(3-acetylamino)alanine methyl ester N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methy lpenty l]-N-( 1 -naphthylmethyl)glycyl-(3-acetylamino)alanine N-[2(S)-([ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-2(RS) amino-3-(2 thienyl)propionic acid methyl ester N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpenty l]-N-( 1 -naphthylmethyl)glycyl-2(RS)-amino-3-(2 thienyl)propionic acid N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methy lpenty l]-N-( 1 -naphthylmethyl)glycyl-2(S) amino-4-sulfamyl- butanoic acid methyl ester 5 N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-2(S) amino-4-sulfamyl- butanoic acid N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- i o methylpentyl]-N-( 1 -naphthylmethyl)glycyl-N-methy 1 methionine methyl ester N-[2(S)-([ l-(4-cyanobenzyl)-lH-imidazol-5-yllacetylamino)-3(S)- methy lpenty 1]-N-(1 -naphthylmethyl)glycyl-N-methyl methionine 15 N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl)glycyl-homoserine lactone N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- 0 methylpentyl]-N-(l-naphthylmethyl)glycyl-homoserine N-[2(S)-([l -(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-proline methyl ester 5 N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-( 1 -naphthylmethyl )glycy 1-proline N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-D-proline methyl ester 0 N-[2(S)-([l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetylamino)-3(S)- methylpenty l]-N-( 1 -naphthylmethyl)glycyl-D-proline N-[2(S)-([ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetylamino)-3(S)- methylpentyl]-N-(l-naphthylmethyl)glycyl-L- pipecolinic acid N-[2(S)-([ 1 -(4-carbomethoxybenzyl)- 1 H-imidazol-5-yl]acetylamino)- 5 3(S)-methylpentyl]-N-(l-naphthylmethyl)glycyl-methionine methyl ester N-[2(S)-([ 1 -(4-carbomethoxybenzyl)- 1 H-imidazol-5-yl]acetylamino)- 3(S)-methylpentyl]-N-( 1 -naphthylmethyl)glycyl-methionine i o 1 -(2-naphthy Imethyl)- 1 H-imidazol-5-ylacetyl-isoleucinyl- phenylalaninyl-methionine methyl ester 1 -(2-naphthylmethyl)- 1 H-imidazol-5-ylacetyl-isoleucinyl- phenylalaninyl-methionine 15 or a pharmaceutically acceptable salt thereof. 10. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: 20 N-[2(S)-(l -(4-Nitrophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthylmethyl-glycyl-methionine or a pharmaceutically acceptable salt thereof. 11. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-N'-(l -(4-Nitrophenyl-methyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l -naphthylmethyl-glycyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 12. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine or a pharmaceutically acceptable salt thereof. 13. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 14. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-( 1 -(4-Cyanophenyl-methyl)- lH-imidazol-5-y lacety l)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine isopropyl ester or a pharmaceutically acceptable salt thereof. 15. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Methoxyphenylmethyl)-lH-imidazol-5-ylacetyI)amino- 3(S)-methylpenty 1]-N- 1 -naphthylmethy 1-glycyl-methionine or a pharmaceutically acceptable salt thereof. 16. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-( 1 -(4-Methoxyphenyl-methy 1)- 1 H-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l-naphthylmethyl-glycyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 17. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N- [2(S)-( 1 -(2-Naphthylmethyl)- 1 H-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine or a pharmaceutically acceptable salt thereof. 18. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(2-Naphthylphenyl-methyl)-lH-imidazol-5-ylacetyl)amino- 3(S)-methylpentyl]-N-l -naphthylmethyl-glycyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 19. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N-l-naphthylmethyl-glycyl-methionine sulfone methyl ester or a pharmaceutically acceptable salt thereof. 20. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-yiacetyl)amino-3(S methy lpenty 1]-N- 1 -naphthylmethyl-glycyl-methionine sulfone or a pharmaceutically acceptable salt thereof. 21. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methy lpenty 1]-N- 1 -naphthylmethyl-glycyl-(3-acetylamino)alanine methyl ester or a pharmaceutically acceptable salt thereof. 22. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-(3-acetylamino)alanine methyl ester or a pharmaceutically acceptable salt thereof. 23. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l -(4-Cyanophenylmethyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpenty 1]-N- 1 -naphthylmethyl-glycyl-N-methyl-methionine or a pharmaceutically acceptable salt thereof. 24. A compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[2(S)-(l-(4-Cyanophenyl-methyl)-lH-imidazol-5-ylacetyl)amino-3(S)- methylpentyl]-N- 1 -naphthy Imethy 1-glycyl-N-methyl-methionine methyl ester 10 or a pharmaceutically acceptable salt thereof. 25. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically χ 5 effective amount of a compound of Claim 1. 26. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 2. 20 27. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 3. 25 28. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 4. 29. A pharmaceutical composition comprising a 0 pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 9. 30. A method for inhibiting famesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 25. 31. A method for inhibiting famesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 26. 32. A method for inhibiting famesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 27. o 33. A method for inhibiting famesylation of Ras protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 28. 34. A method for inhibiting famesylation of Ras 5 protein which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 29. 35. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective 0 amount of the composition of Claim 25. 36. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 26. 5 37. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 27. 0 38. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 28. 39. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of the composition of Claim 29.

Inventors: ANTHONY NEVILLE J, DESOLMS S JANE, GOMEZ ROBERT P, GRAHAM SAMUEL L, HUTCHINSON JOHN H, STOKKER GERALD E, ANTHONY, NEVILLE, J., DESOLMS, S., JANE, GOMEZ, ROBERT, P., GRAHAM, SAMUEL, L., HUTCHINSON, JOHN, H., STOKKER, GERALD, E.
Applicants: ANTHONY NEVILLE J, DESOLMS S JANE, GOMEZ ROBERT P, GRAHAM SAMUEL L, HUTCHINSON JOHN H, MERCK & CO INC, STOKKER GERALD E, ANTHONY, NEVILLE, J., DESOLMS, S., JANE, GOMEZ, ROBERT, P., GRAHAM, SAMUEL, L., HUTCHINSON, JOHN, H., MERCK & CO., INC., STOKKER, GERALD, E.
Application year: 1995
Main classification: C07K5
IPC codes: A61K31, A61K38, A61P35, A61P43, C07D233, C07K5