INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

Abstract: The present invention comprises analogs of the CA<1>A<2>X motif of the protein Ras that is modified by farnesylation in vivo. These CA<1>A<2>X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA<1>A<2>X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A<2> position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Description: TITLE OF THE INVENTION INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE RELATED APPLICATION The present patent application is a continuation-in-part application of copending application Serial No. 08/412,828, filed March 29, 1995. BACKGROUND OF THE INVENTION The Ras proteins (Ha-Ras, Ki4a-Ras, Ki4b-Ras and N-Ras) are 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 (Ha-ras, Ki4a-r_«, Ki4b-r_._. and N-ras) 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 1 -Aaa--Xaa" box (Cys is cysTfcine, Aaa is an aliphatic amino acid, the Xaa is any amino acid) (Willumsen et al. Nature 310: ' ~ ' -S ~ ( 1984)). Depending on the specific sequence, this motif serv es as a signal sequence for the enzymes famesyl-protein transferase or geranylgeranvl-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-translational famesylation. Other famesylated 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 famesylated. James, et al., have also suggested that there are famesylated proteins of unknown structure and function in addition to those listed above. Inhibition of famesyl-protein transferase has been shown to block the growth of Ras-transformed cells in soft agar and to modify other aspects of their transformed phenotype. It has also been demonstrated that certain inhibitors of famesyl-protein transferase selectively block the processing of the Ras oncoprotein intracellularly (N.E. Kohl et al, Science, 260:1934-1937 (1993) and G.L. James et al, Science, 260:1937-1942 (1993). Recently, it has been shown that an inhibitor of famesyl-protein transferase blocks the growth of ras- dependent tumors in nude mice (N.E. Kohl et al, Proc. Natl. Acad. Sci U.S.A., 97:9141-9145 (1994) and induces regression of mammary and salivary carcinomas in ras transgenic mice (N.E. Kohl et al, Nature Medicine, 1:792-797 (1995). Indirect inhibition of famesyl-protein transferase in vivo has been demonstrated with lovastatin (Merck & Co., Rahway, NJ) and compactin (Hancock et al, ibid; Casey et al. ibid; Schafer et al, Science 245: ' 19 (1989)). These drugs inhibit HMG-CoA reductase, the rate limiting enzyme for the production of polyisoprenoids including famesyl pyrophosphate. Famesyl-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: 1133-1 139 ( 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 famesyl-protein transferase would be more specific and attended by fewer side effects than would occur with the required dose of a general inhibitor of isoprene biosynthesis. Inhibitors of famesyl-protein transferase (FPTase) have been described in two general classes. The first are analogs of 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, 88:732-136 (1991)). Such inhibitors may inhibit protein prenylation while serving as alternate substrates for the famesyl-protein transferase enzyme, or may be purely competitive inhibitors (U.S. Patent 5,141,851, University of Texas; N.E. Kohl et 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 has recently been reported that famesyl-protein transferase inhibitors are inhibitors of proliferation of vascular smooth muscle cells and are therefore useful in the prevention and therapy of arteriosclerosis and diabetic disturbance of blood vessels (JP H7-1 12930). It has recently been disclosed that certain tricyclic compounds which optionally incorporate a piperidine moiety are inhibitors of FPTase (WO 95/10514, WO 95/10515 and WO 95/10516). Imidazole-containing inhibitors of famesyl protein transferase have also been disclosed (WO 95/09001 and EP 0 675 1 12 Al ). It is, therefore, an object of this invention to develop peptidomimetic compounds that do not have a thiol moiety, and that will inhibit famesyl-protein transferase and thus, the post-translational famesylation of proteins. It is a further object of this invention to develop chemotherapeutic compositions containing the compounds of this invention and methods for producing the compounds of this invention. SUMMARY OF THE INVENTION The present invention comprises analogs of the CA A^X motif of the protein Ras that is modified by famesylation in vivo. These CA! A^X analogs inhibit the famesylprotein transferase. Furthermore, these CA! A^X analogs differ from those previously described as inhibitors of famesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol- dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A^ position of the motif. 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: V - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention inhibit the famesyl-protein transferase. In a first embodiment of this invention, the famesyl-protein transferase inhibitors are illustrated bv the formula I: - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, R ^O-, π S(0) m -, Rl0c(O)NRl0-, CN, Nθ2, (R 10 )2N- C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lOC(O)NRl -, c) C1-C alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, R n S(0) m -, Rl0c(O)NRl0-, CN, (R10)2N-C(NR10)-, Rl C(O)-, RlOθC(O)-, N3, -N(Rl )2, OΓ RHOC(O)- NRlO-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C l -C20 alkyl, C2-C2O alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(Rl0)2, N02, R^O-, Rl l S(0)πr, R 10 C(O)NR l0-, CN, (RlO) 2 N-C(NRlO)-, R 10 C(O)-, R!OOC(0)-, N3, -N(R lO)2. 1 Ϊ QCfONR 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; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C l -C6 alkyl unsubstituted or substituted by alkenyl, R OO-, R n S(0) m -, Rl0c(O)NRl0-, CN, N3, (R10)2N-C(NR10)-, RlOc(O)-, RlOθC(O)-, -N(RlO) 2 , or R 10C(0)NR10-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, R n S(0) m -, Rl0c(O)NRl0-, CN, N02, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; 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 C 1 -C20 alkyl, C2-C2O alkenyl. C3-C10 cycloalkyl, aryl or heterocycle group. wherein the substituent is selected from F, Cl, Br, (RlO)2NC(0)-, Nθ2, R 10 O-, RHS(0) m -, Rl0C(O)NRl -, CN, (RlO)2N-C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, RHOC(O)NR10- and C1-C20 alkyl, d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C10 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(CORlO)- ; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R lS(0) m -, Rl0C(O)NRl0-, CN, Nθ2 . R 10 2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, or R 10C(0)NR1 -, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R O-, RHS(0) m -, R i 0 C(O)NH-, CN, H2N- C(NH)-, RlOC(O)-, RI OC(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F. Cl, Br, R ! 0 O-, Rl l.S(0)m-, Rl°C(O)NRl0-, CN. Nθ2, (R 10 )2N-C- (NRlO)-, RlOC(O)-, R lOθC(O)-. N3. -N(R lO)2, or R l lOC(O)NR 10 -. and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R O-, RHS(0) m -, R10C(0)NR1 -, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, N3, -N(RlO) 2 , OΓ RHOC(O)NR10- ; R O is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl is independently selected from Cl-C6 alkyl and aryl; Al and A^ are independently selected from: a bond, -CH=CH-, -C^≡C-, -C(O)-, -C(O)NRl -, -NR1 C(O)-, O, -N(R1 )-, -S(0)2N(R10)-, -N(RlO)S(0)2-, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicychc ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a 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 Al is a bond, n is 0 and A ~ is S(0)m; 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; t is 3, 4 or 5; and u is O or l; or the pharmaceutically acceptable salts thereof. R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide. or ii) methionine sulfone. and c) substituted or unsubstituted C l -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-, Ri S(0)m-, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRl )-, RlOc(O)-, RlOOC(O)-, N3, -N(RlO)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- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C 1 -Cβ alkyl unsubstituted or substituted by alkenyl, R 1 0 O-, Rl lS(0)m-, R10C(O)NR10-, CN, N3, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl0)2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, R n S(0) m -, RlOC(0)NRlO-, CN. NO2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C 10 cycloalkyl; R a and R5b are independently selected from: a) a side chain of a naturallv occurπnc 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 heterocycle group, wherein the substituent is selected from F, Cl, Br, (RlO)2NC(0)-, N02, R 10 O-, Rl lS(0)m-, Rl0C(O)NRl0-, CN, (Rl )2N-C(NRl )-, RIOC(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0- and C1-C20 alkyl, d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 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(CORlO)- ; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl c(O)NRl0-, CN, N02, Rlθ2N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl. alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, RU S(0) m -, Rl0C(O)NH-, CN, H2N- C(NH)-, RlOC(O)-, RlOθC(O)-. N3, -N(R lO) 2 , or R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R 0θ-, R n S(0) m -, R 10 C(O)NRl0-, CN, N02, (Rl°)2N-C- (NR )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, or RllOC(O)NRl -, and c) C l -C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, Rl O-, Rl lS(0) m -, R1°C(0)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOOC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is a) substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C5-C8 cycloalkyl, or substituted or unsubstituted cyclic amine, wherein the substituted alkyl, cycloalkyl or cyclic amine is substituted with 1 or 2 substituents independently selected from: 1) C1-C6 alkyl, 2) aryl, 3) heterocycle, 5) -ORl0, or R 1 is independently selected from hydrogen and Cl -C6 alkyl; R l4 is independently selected from C] -C6 alkyl: A! and A^ are independently selected from: a bond, -CH=CH-, -C=C-, -C(OK -C(O)NRl -, -NRl C(O)-, O, -N(RlO)-, -S(O)2N(Rl0)-, -N(RlO)S(0)2-, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicyclic ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1 -C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a 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 Al is a bond, n is 0 and A2 is S(0)m", or the pharmaceutically acceptable salts thereof. In a third embodiment of this invention, the inhibitors of famesyl transferase are illustrated by the formula III: V - A 1 (CR 1a 2 ) n A 2 (CR 1 l a a 2 ) n wherein: Rla and Ri are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, Rl^O-, R n S(0) m -, Rl c(O)NRl0-, CN, Nθ2, (Rl°)2N- C(NRl )-, Rl0c(O)-, Rl θC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, R π S(0) m -, RlOC(0)NRlO-, CN, (R10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lθC(0> NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C 1 -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, , wherein the substituent is selected from F, Cl, Br, N(RlO)2, N02. R 10 O-, R l l S(0)rn-. R 10 C(O)NR l0-, CN, (R l0) 2 N-C(NR l0)-, R lOC(O)-, R 10OC(O)-, N3. -N(R l0)2, R 1 1 OC(O)NRl0- and C] -C20 alkyl. and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- Cio cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C 1 -C6 alkyl unsubstituted or substituted by alkenyl, R 1 OO-, R n S(0) m -, R 10 C(O)NRl0-, CN, N3, (R10)2N-C(NR10)-, RlOC(O)-, RlOOC(O)-, -N(RlO) 2 , or Rl lOC(O)NRl -, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, Rl lS(0) m -, Rl°C(O)NRl0-, CN, NO2, (Rl°)2N- C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, or RHOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-. Rl ] S(0) m -, R10QO)NR 1 0 -, CN. N02, R 10 :N-C(NRl0)-. R^CfO)- Rl oC(O)-, N3. -N(R l0)2. or R l lQC(O)NR l0-. and c) C l -C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0) m -, Rl0C(O)NH-, CN, H2N- C(NH)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R IOO-, Rl lS(0)πr, R1°C(0)NR10-, CN, N02, (Rl°)2N-C- (NRlO)-, 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-, RHS(0) m -, R1°C(0)NR10-, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, Rl oC(O)-, N3, -N(RlO) 2 , OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Al and A^ are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(R10)-, -S(O)2N(Rl )-, -N(Rl0)S(O)2-, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicyclic ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle. c) arv . d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m', W is a heterocycle; X, Y and Z are independently H2 or O; or the pharmaceutically acceptable salts thereof. In a fourth embodiment of this invention the prodmgs of compounds of formula III are illustrated by the formula IV: wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, Rl^O-, Rl lS(0) m -, R!0C(O)NR10-, CN, Nθ2, (Rl°)2N- C(NRlO)-, Rl0c(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, R ^O-, R π S(0)πr, Rl°C(O)NRl -, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lθC(0> NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C1-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 -, R!0C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOOC(O)-, N3, -N(RlO)2, R lOC(O)NRl . and C1-C20 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C l -C6 alkyl unsubstituted or substituted by alkenyl, R 1 °0-, R lS(0)m-, Rl°C(O)NRl0., CN, N3, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl0)2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, Nθ2, (Rl°)2N- C(NRl )-, RlOc(O)-, Rl θC(O)-, N3, -N(RlO)2, or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R OO-, Rl lS(0) m -, R10C(O)NR10-, CN, N02, Rlθ2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by aryl, heterocycle, 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(Rl ) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F. Cl, Br, R 1 OO-, R 1 ] S (O)πr, R ! 0C(O)NR 10-, CN. Nθ2, (R ϊ 0 )2N-C- (NRlO)-, R l0C(O)-, RlOθC(O)-. N3, -N ( R lO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, R! C(O)NR -, CN, (RlO)2N-C(NRlO)-, Rl C(O)-, RlOOC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Al and A2 are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, -NR10C(O)-, O, -N(RlO)., -S(0)2N(RlO)-, -N(RlO)S(0)2-, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicychc ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A is S(0)m; or the pharmaceutically acceptable salts thereof. In a more prefeπed embodiment of this invention, the Ras famesyl transferase inhibitors are illustrated by the Formula I: wherein: Rla is independently selected from: hydrogen or Cl-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(R 1°)2 or alkenyl, c) C 1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(Rl°)2; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone. c) substituted or unsubstituted Ci-Cio 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, (RlO) 2 N-C(NRl )., 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; or R2 and R3 are combined to form - (CH2)s - '■ > or R2 or R3 are combined with R6 to form a ring such that R4a and R^a are independently selected from: a) hydrogen, b) C 1 -C6 alkyl unsubstituted or substituted by alkenyl, R IOO-, Rl lS(0)m-, R1°C(0)NR10-, CN, N3, (R10)2N-C(NR10)-, Rl C(O)-, RlOOC(O)-, -N(Rl )2, or Rl lOC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, Rl lS(0) m -, Rl°C(O)NRl0-, CN, NO2, (R 10 )2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3- ClO cycloalkyl; R4b and R 7b are hydrogen; 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-CiO 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-, (Rl0)2NC(O)-, CN, (Rl0)2N-C(NRl )-, R10C(O)-, Rl θC(O)-, N3, -N(RlO)2, RHOC(O)NR1 - 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; R5b is selected from: a) hydrogen, and b) C1-C3 alkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR1 -, CN, N02, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RIOOC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, Rl0C(O)NRl0-, (RlO)2N-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, C l -C6 perfluoroalkyl, F, Cl, RlOO-, Rl ls(0) m -, R1°C(0)NR10-, CN, Nθ2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(RlO) 2 , or RllOC(O)NRl0-, and c) C l -C6 alkyl unsubstituted or substituted by C l -C6 perfluoroalkyl, F, Cl, R OO-, RHS(0) m -, R1°C(0)NR1 -, CN, (RlO)2N-C(NRl )-, RlOc(O)-, RlOoC(O)-, -N(RlO) 2 , OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -G=C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl. d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m * , W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H2 or O; or the pharmaceutically acceptable salts thereof. In a second more preferred embodiment of this invention, the prodmgs of the preferred compounds of Formula I are illustrated by the Formula II: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl: Rlb is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl^O-, -N(RlO)2 or alkenyl, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, or -N(RlO)2; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substituted or unsubstituted C l -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)πr, R10C(0)NR10-, CN, (RlO)2N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, Rl lOC(O)NRl0- and Cl-Qo alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such mat R4a and R7a are independently selected from: a) hydrogen. b) C l -C6 alkyl unsubstituted or substituted by alkenyl, R 10θ-, R π S(0) m -, Rl°C(O)NRl0-, CN, N3, (R1°)2N-C(NR1 )-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or RHOC(O)NR10-, c) aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, Rl lS(0)m-, RlOC(0)NRlO-, CN, Nθ2, (Rl°)2N- C(NRl )-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or RHOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3- C 10 cycloalkyl; R4b and R^b are hydrogen; 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)πr, R1°C(0)NR10-, (RlO) 2 NC(0)-, CN, (Rl ) 2 N-C(NRl0)-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl0)2, RHOC(0)NR10- 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; R5b is selected from: a) hydrogen, and b) C1-C3 alkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C l -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR10-, CN, N02, (Rl )2N-C(NRl )-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, RlOO-, Rl C(O)NRl -, (RlO) 2 N-C(NRlO)-, RlOC(O)-, Rl θC(O)-, -N(RlO)2, or R1 1OC(O)NR10- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C l -Cβ perfluoroalkyl, F, Cl, RlOo-, Rl lS(0)πr, R1°C(0)NR10-, CN, N02, (Rl°)2N- C(NRlO)-, Rl0c(O)-, RlOθC(O)-, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C l -C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m -, R1°C(0)NR1 -, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOOC(O)-, -N(Rl )2, OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1 -C6 alkyl and aryl; Rl is a) substituted or unsubstituted C 1 -C8 alkyl or substituted or unsubstituted C5-C8 cycloalkyl, wherein the substituent on the alkyl or cycloalkyl is selected from: 1 ) aryl. 2) heterocycle, 4) -ORlO, or R 1 . Rl3 is independently selected from hydrogen and Cl-C6 alkyl; Rl4 is independently selected from C1-C6 alkyl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C 1 - 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A is S(0)m and V is not hydrogen if . . is a bond, n is 0 and A- is S(0)π W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H2 or O; 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 III: V - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n wherein: Rla is independently selected from: hydrogen or Cl-C6 alkyl; R ib is independently selected from: a) hydrogen. b) arvl. heterocvcle. cvcloalkvl. R l°0-, -N(R l0)2 or alkenyl. c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(RlO)2; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substituted or unsubstituted 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, R 10 O-, Rl lS(0)m-, R1°C(0)NR10-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, N3, -N(RlO)2, Rl lθC(O)NRl0- and Cl- o alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a and R^ are independently selected from: a) hydrogen, b) C 1 -Cβ alkyl unsubstituted or substituted by alkenyl, R 1 OO-, R l l S(0) m -, Rl0C(O)NR l0-, CN. N3, (RΪ0) 2 N-C(NR10)-, R l0C(O)-, RlOoC(0)-, -N(R lO)2. or Rl lOC(0)NR lO., c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, Nθ2, (R i0 )2N- C(NRlO)-, Rl0c(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3- C 10 cycloalkyl; R4b and R?b are hydrogen; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl π O-, Rl n C(O)NRl0-, CN, Nθ2, (RlO)2N-C(NRlO)-, RlOc(O)-, R10OC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl substituted by C 1 -C6 perfluoroalkyl, R 1 °0-, Rl C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl )2, or Rl lθC(0)NRl π -; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C l -Cβ perfluoroalkyl, F, Cl, RlOo-, Rl lS(0) m -. R 10 C(O)NRl0-, CN, N02, (Rl°)2N- C(NRl )-, RlOc(O)-, R lOθC(O)-, -N(Rl0) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by C l -C6 perfluoroalkyl, F, Cl, RlOO-, R ] l S(0) m -, R! C(O)NR 10-, CN, (R 10) 2 N-C(NR10)-, RlOc(O)-, R lOθC(O)-, -NCR 10)2, or Rl lOC(O)NRl0-; R lO is independently selected from hydrogen. C j -Cό alkyl. benzyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinohnyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A is S(0)m; W is a heterocycle selected from pyrrolidinyl. imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl. quinolinyl, or isoquinolinyl; X, Y and Z are independently H2 or O; m is 0. 1 or 2; or the pharmaceutically acceptable salts thereof. In a fourth more preferred embodiment of this invention, the prodmgs of the preferred compounds of Formula III are illustrated by the Formula IV: wherein: Rla is independently selected from: hydrogen or Cl-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R 10 ( 3-, -N(R 10)2 or alkenyl, c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, R °0-, or -N(Rl°)2; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, 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, R 10 O-, Rl lS(0)m-, R 10 C(O)NRl0_, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl )2, Rl lOC(O)NRl0- and Cl- O alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a and R^a are independently selected from: a) hydrogen, b) C 1 -C6 alkyl unsubstituted or substituted by alkenyl, R 1 O-, R π S(0) m -, Rl0C(O)NRl0-, CN, N3, (R10) 2 N-C(NR10)-, Rl C(O)-, RI OC(O)-, -N(Rl0)2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl O-, Rl l S(0)m-, R 10 C(O)NRl0-, CN. N02, (Rl ) 2 N- C(NRlO)-, Rl C(O)-, RIOOC(O)-, N3, -N(Rl ) 2 , OΓ RHOC(O)NR10., and d) C 1 -C6 alkyl substituted with an unsubstituted or substituted group selected from aryl. heterocyclic and C3- C 10 cycloalkyl; R4b and R?b re hydrogen; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl O-, R!0C(O)NR1 -, CN, NO2, (Rl )2N-C(NRl )-, RlOc(O)-, Rl oC(O)-, -N(RlO) 2 , or RHθC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, Rl°0-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRl )-, Rl0c(O)-, Rl θC(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C 1 -Cβ perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)m-, R1°C(0)NR10-, CN, Nθ2, (Rl°)2N- C(NRl )-, RlOC(O)-, RIOOC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c ) C l -Cβ alkyl unsubstituted or substituted by C l -Cβ perfluoroalkyl, F, Cl, Rl O-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOoC(O)-, -N(Rl ) 2 , OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1 -C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, o, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyπolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) Ci-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m", W is a heterocycle selected from pyπolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H2 or O; or the pharmaceutically acceptable salts thereof. The prefeπed compounds of this invention are as follows: N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyπolidin-2(S)-ylmethyl]- prolyl-methionine methyl ester N-[ 1 -( lH-Imidazol-4-ylacetyl)-3(S)-ethylpyπolidin-2(S)-ylmethyl]- prolyl-methionine N-[ 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfone isopropyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfoxide N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfoxide isopropyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyllpyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfone N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ l-( lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine methyl ester N-[ l -( l H-Imidazol-4-ylacetyl)-pyrrolidin-2(S >-ylmethyl]-3(S)-ethyl- prolyl-methionine N- [ 1 -Glycyl-pyπolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[l-Glycyl-pyπolidin-2(S)-ylme_hyl]-3(S)-ethyl-prolyl-methionine N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyπolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyπolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine N-[l-[3-(l -(4-Cyanobenzyl)- lH-imidazol-5-yl)propionyl]p τrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[ 1 -[3-( 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)propionyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[2(S)-(lH-Imidazol-4-ylacetyl-amino)-3(S)-methylpentyl]-prolyl- methionine methyl ester N- [2(S )-( 1 H-Imidazol-4-ylacety 1-amino)- 3 (S )-methy lpentyl]-proly 1- methionine N-[ 1 -( 1 H-Imidazol-4-ylacetyl)-pyπolidin-2(S-)ylmethyl]-prolyl- methionine methyl ester N-[l-(lH-Imidazol-4-ylacetyl)-pyπolidin-2(S-)ylmethyl]-prolyl- methionine N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-prolyl-methionine methyl ester N-[ l-[ l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-prolyl-methionine N-[ l -( lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyιτolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine N- [ 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacety l]-3 (S)-ethylpyπolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N- [ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]-3 (S)-ethylpyπolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]-3(S)-ethylpyπolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester N-[l-(3-[lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N- [ 1 -(3-[ 1 H-Imidazol-4-yl]propionyl)-3 (S)-ethylpyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-Glycyl-3(S)-ethylpyπolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine methyl ester N-[l-Glycyl-3(S)-ethylpyπolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine N-[ 1 - [ 1 -(4-Nitrobenzyl)- 1 H-imidazol-4-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ 1 -[ 1 -(4-Nitrobenzyl)- 1 H-imidazol-5-ylacetyl] pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ 1 -( 1 -( 1 -Famesyl)- 1 H-imidazol-5-ylacetyl)-pyrτolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl methionine N-[ 1 -( 1 -( 1-Geranyl)- lH-imidazol-5-ylacetyl)-pyπolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl-methionine N-[ 1 -[ 1 -(4-Methoxybenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-[l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]pyπohdin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine and N-[l-(lH-Imidazol-4-ylacetyl)-pyπolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-(β-acetylamino)alanine or the pharmaceutically acceptable salts thereof. Specific examples of compounds of the invention are: N-[l-(lH-Imidazol-4-ylacetyl)-pyπolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine N-[l-(lH-Imidazol-4-ylacetyl)-ρyπolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine methyl ester N-[ 1 -(3-[ 1 H-Imidazol-4-yl]propionyl)-pyπolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine N-[l-(3-[lH-Imidazol-4-yl]propionyl)-pyπolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester N-[ l-(3-[ lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-ρrolyl-methionine N-[l-(3-[lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyπolidin-2(S)- ylmethyl]-3(S)-ethyl-ρrolyl-methionine methyl ester N-[2(S)-(lH-Imidazol-4-ylacetyl-amino)-3(S)-methylpentyl]-prolyl- methionine methyl ester N-[2(S)-( lH-Imidazol-4-ylacetyl-amino)-3(S)-methylpentyl]-prolyl methionine N-[ l-[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyπolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl 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 heterocycle ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic elements include, but are not limited to, azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofiiryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihy drobenzofuryl, dihydro- benzothienyl, dihydrobenzothiopyranyl, dihydrobenzothio-pyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, mo holinyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyπolidinyl, piperidyl, piperazinyl, pyridyl, pyridyl N-oxide, pyridonyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyrimidinyl, pyπolidinyl, pyπolyl, 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, CF3, NH2, N(C_ - C6 alkyl)2, Nθ2, CN, (Cl-C6 alkyl. O-, -OH, (C 1 -C6 alkyl)S(0) m -, (Cl- C6 alkyl)C(0)NH-, H2N-C(NH)-, (Cl -C6 alkyl)C(O)-, (Cl-C6 alkyl)OC(O)-, N3,(C l-C6 alkyl)OC(0)NH- and Cl-C20 alkyl. The following structure: represents a cyclic amine moiety having 5 or 6 members in the ring, such a cyclic amine which may be optionally fused to a phenyl or cyclohexyl ring. Examples of such a cyclic amine moiety include, but are not limited to, the following specific structures: It is also understood that substitution on the cyclic amine moiety by R^a and R^b may be on different carbon atoms or on the same carbon atom. When 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 R5 and R^b are combined to form - (CH2)s -» cyclic moieties as described hereinabove for R and R^ 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: As used herein, the phrase "nitrogen containing C4-C9 mono or bicychc ring system wherein the non-nitrogen containing ring may be a C5-C7 saturated ring" which defines moiety "Q" of the instant invention includes but is not limited to the following ring systems: The pharmaceutically acceptable salts of the compounds of this invention include the conventional non-toxic salts of the compounds of this invention as formed, e.g.. from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like: and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenyl- acetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxy-benzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, trifluoroacetic and the like. It is intended that the definition of any substituent or variable (e.g., RlO, Z, n, etc.) at a particular location in a molecule be independent of its definitions elsewhere in that molecule. Thus, -N(Rl )2 represents -NHH, -NHCH3, -NHC2H5, etc. It is understood that substituents and substitution patterns on the compounds of the instant invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art as well as those methods set forth below. Preferably, Rla and Rib are independently selected from: hydrogen, -N(R8)2, R 8 C(0)NR8- or -C6 alkyl unsubstituted or substituted by -N(R8)2, R80- or R8C(0)NR8-. Preferably, R2 is the sidechain of glycine (hydrogen). Preferably, R3 is selected from: a) a side chain of a naturally occurring amino acid, b) substituted or unsubstituted C1-C2O alkyl, wherein the substituent is selected from F, Cl, Br, N(RlO)2, Nθ2, Rl°0-, Rl lS(0)πr. R 10 C(O)NRl0_, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(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- ClO cycloalkyl; or R3 is combined with R6 to form pyπolidinyl ring. Preferably, R4a, R4b, R7a and R 7b are independently selected from: hydrogen, C 1-C6 alkyl. aryl and benzyl. 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, R6 is: hydrogen or is combined with R3 to form pyπolidinyl ring. Preferably, R8 is selected from: hydrogen, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -. CN, NO2, Rl 2N-C(NR )-, RlOc(O)-, Rl θC(O)-, N3, -N(Rl )2, or RHOC(0)NR10- and C1-C6 alkyl. Preferably, R^ is hydrogen. Preferably, Rl is selected from H, C1-C6 alkyl and benzyl. Preferably, R 1 is selected from C 1 -C6 alkyl and benzyl. Preferably, Al and A2 are independently selected from: a bond, -C(O)NRl0-, -NR10C(O)-, O, -N(R10)-, -S(O)2N(Rl0)- and- Preferably, Q is a pyπolidinyl ring. Preferably, V is selected from hydrogen, heterocycle and aryl. 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 can be synthesized from the compounds of this invention which contain a basic moiety conventional chemical methods. Generally, the salts are prepared by ion exchange chromatography or 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: Compounds of this invention are prepared by employing the reactions shown in the following Reaction Schemes A-J, in addition to other standard manipulations such as ester hydrolysis, cleavage of protecting groups, etc., as may be known in the literature or exemplified in the experimental procedures. Some key bond-forming and peptide modifying reactions are: Reaction A Amide bond formation and protecting group cleavage using standard solution or solid phase methodologies. Reaction B Preparation of a reduced peptide subunit by reductive alkylation of an amine by an aldehyde using sodium cyanoborohydride or other reducing agents. Reaction C Deprotection of the reduced peptide subunit 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. 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: 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 the Reaction Schemes. REACΗON CHEME A Reaction A. Coupling of residues to form an amide bond REACΉON SCHEME B Reaction B. Preparation of reduced peptide subunits by reductive alkylation REACΉON SCHEME C Reaction C. Deprotection of reduced peptide subunits REACΉON 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 is R2, R3, R5a or R5b a s previously defined; R4a and R4b are as previously defined; and R is an appropriate protecting group for the carboxylic acid. Reaction Schemes F - 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. It is well understood that such reactions are equally useful when the - NHC(R A ) - moiety of the reagents and compounds illustrated is replaced with the following 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 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 I, as shown in Reaction Scheme F. 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 F). 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 II can be deprotected to give the final compounds HI with trifluoroacetic acid in methylene chloride. The final product HI is isolated in the salt form, for example, as a trifluoroacetate, hydrochloride or acetate salt, among others. The product diamine ffl can further be selectively protected to obtain IV, which can subsequently be reductively alkylated with a second aldehyde to obtain V. Removal of the protecting group, and conversion to cyclized products such as the dihydroimidazole VII can be accomplished by literature procedures. Alternatively, the protected dipeptidyl analog intermediate can be reductively alkylated with other aldehydes such as l-trityl-4- carboxaldehyde or l-trityl-4-imidazolylacetaldehyde, to give products such as VIH (Reaction Scheme G). T e trityl protecting group can be removed from Vffl to give IX, or alternatively, VTII can first be treated with an alkyl halide then subsequently deprotected to give the alkylated imidazole X. Alternatively, the dipeptidyl analog intermediate can be acylated or sulfonylated by standard techniques. The imidazole acetic acid XI can be converted to the acetate XIII by standard procedures, and XIII can be first reacted with an alkyl halide. then treated with refluxing methanol to provide the regiospecifically alkylated imidazole acetic acid ester XIV. Hydrolysis and reaction with the protected dipeptidyl analog intermediate in the presence of condensing reagents such as l-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC) leads to acylated products such as XV. If the protected dipeptidyl analog intermediate is reductively alkylated with an aldehyde which also has a protected hydroxyl group, such as XVI in Reaction Scheme I, the protecting groups can be subsequendy removed to unmask the hydroxyl group (Reaction Schemes I, J). The alcohol can be oxidized under standard conditions to e.g. an aldehyde, which can then be reacted with a variety of organometallic reagents such as Grignard reagents, to obtain secondary alcohols such as XX. In addition, the fully deprotected amino alcohol XXI can be reductively alkylated (under conditions described previously) with a variety of aldehydes to obtain secondary amines, such as XXII (Reaction Scheme K), or tertiary amines. The Boc protected amino alcohol XVm can also be utilized to synthesize 2-aziridinylmethylpiperazines such as XXIII (Reaction Scheme L). Treating XVπi with l, -sulfonyldiimidazole and sodium hydride in a solvent such as dimethylformamide led to the formation of aziridine XXHI . The aziridine reacted in the presence of a nucleophile, such as a thiol, in the presence of base to yield the ring-opened product xxrv . In addition, the protected dipeptidyl analog intermediate can be reacted with aldehydes derived from amino acids such as O-alkylated tyrosines, according to standard procedures, to obtain compounds such as XXX, as shown in Reaction Scheme M. When R' is an aryl group, XXX can first be hydrogenated to unmask the phenol, and the amine group deprotected with acid to produce XXXI. Alternatively, the amine protecting group in XXX can be removed, and O-alkylated phenolic amines such as XXXπ produced. Similar procedures as are illustrated in Reaction Schemes F- M may be employed using other peptidyl analog intermediates such as those whose synthesis is illustrated in Reaction Schemes B - E. Reaction Schemes N-R illustrate syntheses of suitably substituted aldehydes useful in the syntheses of the instant compounds wherein the variable W is present as a pyridyl moiety. Similar synthetic strategies for preparing alkanols that incoφorate other heterocyclic moieties for variable W are also well known in the art. REACΉON CHEME F REACΗON SCHEME F (continued _ REACΗON SCHEME G REACΗON SCHEME H XI X " XIII XIV Ar^\ CH 2 C0 2 H REACΉON SCHEME I REACΗON SCHEME J XVI REACΗON SCHEME J (CONTINUED . REACΗON SCHEME K REACΗON SCHEME L REACΗON SCHEME M XXV XXVI XXVII XXVIII XXIX REACTION SCHEME M (continued . REACΉON SCHEME N NaBH 4 (excess) REACTION SCHEME P REACΗON SCHEME O NaBH 4 (excess) REACΗON SCHEME R 2. (CH 3 ) 3 SiCHN 2 excess NaBH 4 The instant compounds are useful as pharmaceutical agents for mammals, especially for humans. These compounds may be administered to patients for use in the treatment of cancer. Examples of the type of cancer which may be treated with the compounds of this invention include, but are not limited to, colorectal carcinoma, exocrine pancreatic carcinoma, myeloid leukemias and neurological tumors. Such tumors may arise by mutations in the ras genes themselves, mutations in the proteins that can regulate Ras formation (i.e., neurofibromin (NF-1), neu, scr, abl, lck, fyn) or by other mechanisms. The compounds of the instant invention inhibit famesyl- protein transferase and the famesylation of the oncogene protein Ras. The instant compounds may also inhibit tumor angiogenesis, thereby affecting the growth of tumors (J. Rak et al. Cancer Research, 55:4575- 4580 (1995)). Such anti-angiogenesis properties of the instant compounds may also be useful in the treatment of certain forms of blindness related to retinal vascularization. The compounds of this invention are also useful for inhibiting other proliferative diseases, both benign and malignant, wherein Ras proteins are aberrantly activated as a result of oncogenic mutation in other genes (i.e., the Ras gene itself is not activated by mutation to an oncogenic form) with said inhibition being accomplished by the administration of an effective amount of the compounds of the invention to a mammal in need of such treatment. For example, a component of NF-1 is a benign proliferative disorder. The instant compounds may also be useful in the treatment of certain viral infections, in particular in the treatment of hepatitis delta and related viruses (J.S. Glenn et al. Science, 256: 1331-1333 (1992). The compounds of the instant invention are also useful in the prevention of restenosis after percutaneous transluminal coronary angioplasty by inhibiting neointimal formation (C. Indolfi et al. Nature medicine, 1 :541-545( 1995). The instant compounds may also be useful in the treatment and prevention of polycystic kidney disease (D.L. Schaffner et al. American Journal of Pathology, 142:1051-1060 (1993) and B. Cowley, Jr. et zά.FASEB Journal, 2:A3160 (1988)). 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 farnesylate the substrate, the chemical content of the assay mixtures may be determined by well known immunological, radiochemical or chromatographic techniques. Because the compounds of the instant invention are selective inhibitors of FPTase, absence or quantitative reduction of the amount of substrate in the assay mixture without the compound of the instant invention relative to the presence of the unchanged substrate in the assay containing the instant compound is indicative of the presence of FPTase in the composition to be tested. It would be readily apparent to one of ordinary skill in the art that such an assay as described above would be useful in identifying tissue samples which contain famesyl-protein transferase and quantitating the enzyme. Thus, potent inhibitor compounds of the instant invention may be used in an active site titration assay to determine the quantity of enzyme in the sample. A series of samples composed of aliquots of a tissue extract containing an unknown amount of famesyl- protein transferase, an excess amount of a known substrate of FPTase (for example a tetrapeptide having a cysteine at the amine terminus) and famesyl pyrophosphate are incubated for an appropriate period of time in the presence of varying concentrations of a compound of the instant invention. The concentration of a sufficiendy 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-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrohdin-2(S)- ylmethyl]-prolyl-methionine methyl ester and N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpy_τolidin-2(S)-ylmethyl]- prolvl-methionine trifluoroacetate Step A: Preparation of Diethyl l-acetyl-5-hydroxy-3- ethvlpvrrolidine-2.2-dicarboxvlate Sodium (4.02 g, 0.175 mol) was dissolved in a stirred solution of diethyl acetamidomalonate (235.4 g, 1.19 mol) in abs EtOH (1.4 L) at ambient temperature under argon. The reaction mixture was cooled to 0°C, and trans-2-pentenal (100 g, 1.08 mol) was added dropwise maintaining the reaction temperature at <5°C. After the addition, the reaction was allowed to warm to room temperature, stirred for 4 h, then quenched with acetic acid (28 mL). The solution was concentrated in vacuo, and the residue dissolved in EtOAc (1.5 L), washed with 10% NaHCθ3 solution (2 x 300 mL), brine, and dried (MgSθ4). The solution was filtered and concentrated to 700 mL, then heated to reflux and treated with hexane (1 L). On cooling, the title compound precipitated and was collected, mp 106 - 109°C. *H NMR (CD3OD) δ 5.65 (d, IH, J= 5 Hz), 4.1 - 4.25 (m, 4H), 2.7-2.8 (m, IH), 2.21 (s, 3H), 2.10 (dd, IH, J = 6, 13, Hz),1.86- 1.97 (m, 2H), 1.27 (t, 3H, J= 7 Hz), 1.23 (t, 3H, J= 7 Hz), 1.1- 1.25 (m, IH), 0.97 (t, 3H, J= 7 Hz). Step B: Preparation of Diethyl l-acetyl-3-ethylpyrrolidine-2,2- dicarboxylate To a solution of diethyl l-acetyl-5-hydroxy-3- ethylpyrrolidine-2,2-dicarboxylate (287 g, 0.95 mol) and triethylsilane (228 mL, 1.43 mol) in CH2CI2 (3 L) under argon was added trifluoroacetic acid (735 mL, 9.53 mol) dropwise with stirring while maintaining the internal temperature at 25 °C by means of an ice bath. After stirring for 3 h at 23°C, the solution was concentrated in vacuo. . the residue diluted with CH CI2 ( 1.5 L), then treated with H2O ( 1 Li and solid Na2C03 with vigorous stirring until the solution was basic. The organic layer was separated, dried (Na2Sθ4), filtered, then concentrated to give the title compound as a yellow oil which was used without further purification. Step C: Preparation of 3-Ethylproline hydrochloride (Cis:Trans Mixture. Diethyl l-Acetyl-3-ethylpyrrolidine-2,2-dicarboxylate (373 g, 0.95 mol) was suspended in 6N HCI (2 L) and HOAc (500 mL) and heated at reflux for 20 h. The reaction mixture was cooled, washed with EtOAc (IL), then concentrated in vacuo to give an oil which crystallized upon trituration with ether to give the title compound. lH NMR (D2θ) 6 4.23 (d, IH, J= 8 Hz), 3.84 (d, IH, J= 8 Hz), 3.15- 3.4 (m, 4H), 2.33- 2.44 (m, IH), 2.19-2.4 (m, IH), 2.02- 2.15 (m, 2H), 1.53- 1.72 (m, 3H), 1.23- 1.43 (m, 2H), 1.0- 1.15 (m, IH), 0.75 - 0.83 (m, 6H). Step D: Preparation of N-[(tert-Buty\oxy)caιbony\]-cis:trans-3- ethvlproline methvl ester 3-Ethylproline hydrochloride (Cis:Trans Mixture) (20 g, 0.11 mol) was dissolved in CH3OH (200 mL), and the solution was saturated with HCI gas, then stirred at 23 °C for 24 h. Argon was bubbled through the solution to remove excess HCI. The solution was treated with NaHC03 (>84 g) to a pH of 8, then di- rf-butyl dicarbonate (25.1 g, 0.115 mol) dissolved in CH3OH (20 mL) was added slowly. After stirring for 18 h at 23°C, the mixture was filtered, the filtrate concentrated, and the residue triturated with EtOAc, filtered again, and concentrated to give the title compound as an oil. Step E: Preparation of N-[(r_ , rt-Butyloxy)carbonyl]-rr__j.5-3- ethylproline and N-[(t -Butyloxy)carbonyl]-c/s-3- ethylproline methyl ester N-[(rt?rr-Butyloxy)carbonyl]- Λ.tr_2/.5-3-ethylproline methyl ester (29.1 g, 0.1 13 mol) was dissolved in CH3OH ( 1 14 mL) with cooling to 0°C. then treated with 1 N NaOH ( 1 14 mL). After stirring for 20 h at 23°C, the solution was concentrated to remove the CH3OH and then extracted with EtOAc (3 x). The organic layers were combined, dried (MgSθ4), filtered, and concentrated to give 12.8 g of N-[(tert- Butyloxy)carbonyl]-ris-3-ethylproline methyl ester as an oil. The aqueous layer was acidified with solid citric acid and extracted with EtOAc (2 x), the organic layers combined, dried (MgSθ4), filtered, and concentrated to give N-[(te/?-Butyloxy)carbonyl]-frans-3-ethylproline as an oil. *H NMR (CD3OD) δ 3.86 and 3.78 (2 d, IH, J = 6 Hz), 3.33 - 3.58 (m, 2H), 2.01 - 2.22 (m, 2H), 1.5 - 1.74 (m, 2H), 1.33 - 1.5 (m, IH), 1.45 and 1.42 (2 s, 9H), 0.98 (t, 3H, J= 8 Hz). Step F: Preparation of 3(S)-Ethyl-2(S .-proline hydrochloride N-[(te^Butyloxy)carbonyl]-frαns-3-ethylproline (15.5 g, 0.064 mol), S-α-methylbenzylamine (9.03 mL, 0.070 mol), HOBT (10.73 g, 0.70 mol), and N-methylmorpholine (8 mL, 0.076 mol) were dissolved in CH2CI2 (150 mL) with sitπing in an ice-H2θ bath, treated with EDC (13.4 g, 0.070 mol) stirred at 23°C for 48 h. The reaction mixture was partitioned between EtOAc and 10% citric acid solution, the organic layer washed with satd NaHC03 solution, brine and dried (MgS04), filtered, and concentrated to give an oil. This oil was dissolved in a minimum amount of ether (10 mL) to crystallize the desired S,S,S diastereomer (4.2 g), mp 118-121°C. A solution of this product in 8N HCI (87 mL) and glacial acetic acid (22 mL) was heated at reflux overnight. The solution was concentrated on a rotary evaporator, and the residue taken up in H2O and extracted with ether. The aqueous layer was concentrated to dryness to give a 1: 1 mixture of 3(S)-ethyl-2(S)-proline hydrochloride and α- methy lbenzy lamine . 3(S)-Ethyl-2(S)-proline containing α-methylbenzylamine (2.0 g, 0.0128 mol) was dissolved in dioxane ( 10 mL) and H2O (10 mL) with stirring and cooling to 0°C. N,N-diisopropylethylamine (2.2 mL, 0.0128 mol) and di-t -butyl-dicarbonate (2.79 g, 0.0128 mol) were added and stirring was continued at 23°C for 48 h. The reaction mixture was partitioned between EtOAc (60 mL) and H2O (30 mL), the organic layer washed with 0.5N NaOH (2 x 40 L). the aqueous layers combined and washed with EtOAc ( 30 mL) and this layer back-extracted with 0.5 N NaOH (30 mL). The aqueous layers were combined and carefully acidified at 0°C with IN HCI to pH 3. This mixture was extracted with EtOAc (3 x 40 mL), the organics combined, dried (MgSθ4), filtered and concentrated to give N-[(f,?7?-Butyloxy)carbonyl- 3(S)-ethyl-2(S)-proline as a colorless oil. N-[( /?-Butyloxy)carbonyl- 3(S)-ethyl-2(S)-proline was dissolved in EtOAc (50 mL) and the solution was saturated with HCI gas with cooling in an ice-H2θ bath. The solution was stoppered and stirred at 0°C. for 3 hr. Argon was bubbled through the solution to remove excess HCI, and the solution was concentrated to dryness to give 3(S)-ethyl-2(S)-proline hydrochloride. Step Q: N-r(fgrf-Butvloxv.carbonvn-3(S .-ethvl-2(S .-prolinol 3(S)-Ethyl-2(S)-proline hydrochloride containing α- memylbenzyl∑imine (2.0 g, 0.0128 mol) was dissolved in dioxane (10 mL) and H2θ (10 mL) with stirring and cooling to 0°C. N,N- diisopropylethylamine (2.2 mL, 0.0128 mol) and di-terf-butyl- dicarbonate (2.79 g, 0.0128 mol) were added and stirring was continued at 23°C for 48 h. The reaction mixture was partitioned between EtOAc (60 mL) and H2O (30 mL), the organic layer washed with 0.5N NaOH (2 x 40 mL), the aqueous layers combined and washed with EtOAc ( 30 mL) and this layer back-extracted with 0.5 N NaOH (30 mL). The aqueous layers were combined and carefully acidified at 0°C with IN HCI to pH 2. This mixture was extracted with EtOAc (3 x 40 mL), the organics combined, dried (MgS04), filtered and concentrated to give N-[(tert- Butyloxy)carbonyl~3(S)-ethyl-2(S)-proline as a colorless oil which was used without purification. N-[(tert-Butyloxy)carbonyl]-3(S)-ethyl-2(S)-proline (1.6 g, 6.58 mmol) was dissolved in dry THF (10 mL) and treated with borane (IM in THF, 12.5 mL, 12.5 mmol) with stirring at 0 °C for 2 h, then 23°C for 1 h. The solution was cooled to 0°C, treated with H2O (20 mL), and extracted with EtOAc (2 x 30 mL). The organics were washed with brine, satd NaHCθ3, H2O, dried (MgSθ4). filtered and concentrated to give a viscous oil. The oil was dissolved in CH2CI . filtered through dry Siθ2. and the filtrate concentrated to give the title compound as an oil. ^H NMR (CDC13) δ 4.97 (d, IH, J= 7 Hz), 3.71 (t, IH, J = 8 Hz), 3.51-3.62 (m, 3H), 3.18 - 3.26 (m, IH), 1.9 - 2.0 (m, IH), 1.53-1.7 (m, 2H), 1.47 (s, 9H), 1.26 - 1.43 (m, 2H), 0.95 (t, 3H, J = 7 Hz). Step H: N-r(r -Butyloxy.carbonyll-3(S .-ethyl-2(S)-prorinal N-[(f^rr-Butyloxy)carbonyl-3(S)-ethyl-2(S)-prolinol (0.638 g, 2.78 mmol) and E_3N (1.4 mL, 9.74 mmol) were dissolved in dry CH2CI2 (10 mL) with stirring and cooling to -10°C and treated dropwise with a solution of Sθ3.pyr (1.33 g, 8.35 mmol) in dry DMSO (5 mL) keeping the reaction mixture temperature at < 0°C. The mixture was stirred at 0°C. for 20 min then at 5°C for 20 min, and at 15°C for 1 h, then poured into ice-cold 0.5 N HCI and the layers separated. The aqueous layer was extracted with CH2CI2 (3 x 20 mL), organics combined, washed with H2O, aq satd NaHCθ3 solution, brine, and dried (Na2Sθ4). Filtration and concentration to dryness gave the title compound which was used without purification. Step I: N-[( rt-Butyloxy)carbonyl-3(S)-ethylpyιτo_idin-2(S)- ylmethyl 1-proline methyl ester N-[(rerf-Butyloxy)carbonyl]-3(S)-ethyl-2(S)-prolinal (0.315 g, 0.0014 mol) and proline methyl ester hydrochloride (0.233 g, 0.0014 mol) were dissolved in MeOH (5 mL) at ambient temperature under argon with cooling in an ice-H2θ bath, and treated with sodium cyanoborohydride (0.131 g, 0.002 mol) with stirring. After 18 h the mixture was poured into 5% NaHC03 solution (20 mL), the CH3OH removved and the aq layer washed with EtOAc (3 x 30 mL), the organics combined, washed with brine, and dried (MgSθ4). Filtration and concentration to dryness gave the title compound as a colorless oil after chromatography (Siθ2, hexane: EtOAc, 6: 1 ). 1 H NMR (CDCI3) δ 3.70 (s, 3H), 3.1 - 3.7(m, 5H), 2.2 - 2.65 (m. 4H), 1.7 - 2.15 (m, 5H), 1.5 - 1.65 (m, I H), 1.46 (s, 9H), 1.2 - 1.5 (m, 2H). 0.93 (t, 3H, J = 7 Hz). Step J: N-[(fcrt-Butyloxy)carbonyl-3(S)-ethylpyrrohdin-2(S)- ylmethyll-proline N-[(rf?rf-Butyloxy)carbonyl-3(S)-ethylpyrrohdin-2(S)- ylmethylj-proline methyl ester 0.081 g, 0.238 mmol) was dissolved in CH3OH (2 mL), cooled to 0°C and treated with IN NaOH solution (0.952 mL, 0.952 mmol). After stirring at 23°C for 3h, the solution was neutralized with IN HCI (0.952 mL, 0.952 mmol), concentrated to remove the CH3OH, then lyophilized and the residue used as is. Step K: N-[(terf-Butyloxy)carbonyl-3(S)-ethylpyrtolidin-2(S)- ylmethyl ■-prolyl-methionine methyl ester N-[(rerf-Butyloxy)carbonyl-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-proline (0.238 mmol), HOBT (0.048 g, 0.262 mmol), EDC (0.068 g, 0.0357 mmol), and methionine methyl ester hydrochloride (0.048 g, 0.238 mmol) were dissolved in CH2CL2 (10 mL) and stirred at 23°C for 18 h. EtOAc (100 mL) was added, and the mixture washed with satd NaHC03 solution, H2O, brine, and dried (MgS04). Filtration and concentration to dryness gave 0.085 g of title compound. *H NMR (CD3OD) δ (major rotamer) 4.63 (t, IH, J = 7 Hz), 3.73 (s, 3H), 3.55 - 3.7 (m, IH), 3.0-3.5 (m, 4H), 2.3 - 2.7 (m, 5H), 1.9 - 2.2 (m, 3H), 2.08 (s, 3H), 1.6 - 1.9 (m, 4H), 1.46 (s, 9H), 1.3 - 1.45 (m, 2H), 0.92 - 1.02 (m, 3H). Step L: N-[3(S)-Ethylpyrrolidin-2(S)-ylmethyl]-prolyl-methionine methyl ester hydrochloride HCI gas was bubbled into a solution of N-[(tert- butyloxy)carbonyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-prolyl methioninine methyl ester (0.085 g, 0.18 mmol) in EtOAc (5 mL) with stirring and cooling in an ice-H2θ bath until saturation. The solution was stoppered and stirred at 0°C for 2 h, then purged with Ar and concentrated to give the title compound as a yellow foam. Step M: N-[ l-( lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)- lmethyll-prolyl-methionine methyl ester N-[3(S)-Ethylpyrrolidin-2(S)-ylmethyl]-prolyl methionine methyl ester hydrochloride (0.075 g, 0.169 mmol), lH-imidazol-4- ylacetic acid (0.052 g, 0.253 mmol), HOBT (0.34 g, 0.253 mmol), EDC (0.49 g, 0.253 mmol) and Et3N ( 0.176 mL, 1.27 mmol) were dissolved in DMF (4 mL) and stirred at 23°C for 18 h. The solvent was removed in vacuo, EtOAc (60 mL) was added, and the solution was washed sequentially with satd NaHCθ3 solution, H2θ, brine, and dried (MgSθ4). Filtration and concentration to dryness gave the title compound after chromatography (Siθ2, 5 - 10% CH3OH/CH2CI2). H NMR (CD3OD) δ (major rotamer) 7.62 (s, IH), 6.93 (s, IH), 4.6 - 4.67 (m, IH), 4.1-4.16 (m, IH), 3.74 (s, 3H), 3.65 (s, 2H), 3.5 - 3.68 (m, 2H), 3.2 - 3.25 (m, IH), 3.04 - 3.1 (m, IH), 2.44 - 2.7 (m, 5H), 2.05 - 2.26 (m, 4H), 2.08 (s, 3H), 1.68 - 1.87 (m, 4H), 1.26 - 1.5 (m, 3H), 0.99 (t, 3H, J = 7 Hz). FAB MS 480 (M + 1). Step N: N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpy_τohdin- 2(SV ylmethvll-prolvl-methionine trifluoroacetate N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-prolyl-methionine methyl ester (0.020 g, 0.042 mmol) was dissolved in CH3OH (2 mL) at 0°C and treated with IN NaOH solution (0.167 mL, 0.167 mmol) with stirring. After 5 h at 23°C IN HCI (0.167 mL, 0.167 mmol) was added and the mixture was purified by preparative RP HPLC on a Vydac column eluting with 0.1% TFA/CH3CN: 0.1% TFA/ H2θ gradient to give the title compound. lH NMR (CD3OD) δ 8.88 (d, IH, J = IHz)), 7.43 (d, IH, J = IHz), 4.53 - 4.58 (m, IH), 4.25-4.31 (m, IH), 3.96 (ABq, 2H), 3.7 - 3.85 (m, 3H), 3.58 - 3.66 (m, IH), 3.50 (dd, IH, J = 3, 14 Hz), 3.39 (dd, IH, J = 3, 14 Hz), 3.23 - 3.42 (m, IH), 2.45 - 2.67 (m, 3H), 2.12 - 2.28 (m, 4H), 2.08 (s, 3H), 1.98 - 2.05 (m, 3H), 1.54 - 1.68 (m , 2H), 1.26 - 1.4 (m, IH), 1.03 (t, 3H, J = 7 Hz). FAB MS 466 (M + 1 ). EXAMPLE 2 Preparation of N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5- ylacetyl]pyrtθlidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester Step A: N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-3(S)- ethvl-proline 3(S)-Ethyl-2(S)-proline hydrochloride (from Example 1, Step F) (2.33 g, 0.013 mol) was dissolved in CH3OH (20 mL), treated with 3 A molecular sieves (2 g) and KOAc (1.27 g, 0.013 mol) to adjust the pH of the reaction mixture to 4.5-5, then N-[(tert- Butyloxy)carbonyl-prolinal (Pettit et al., J. Org. Chem. (1994) 59, [21] 6287-95) (3.36 g, 0.017 mol) was added, and the mixture was stirred for 16 hrs at room temperature. The reaction mixture was filtered, quenched with aq satd NaHCθ3 (5 mL) and concentrated to dryness. The residue was extracted with CHCI3. The extract was dried (MgSθ4), filtered, and concentrated to give the title compound and inorganic salts. Step B: N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine isopropyl ester N-[(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-proline (2.4 g, 0.008 mol), methionine isopropyl ester hydrochloride (2.21 g, 0.0097 mol), HOBT (1.49 g, 0.0097 mol) and EDC (1.86 g, 0.0097 mol) were dissolved in DMF (15 mL) at room temperature and treated with N-methylmorpholine (3 mL, 0.024 mol). The reaction mixture was stirred overnight at room temperature, then concentrated and partitioned between EtOAc and H2θ. The organic layer was washed with aq satd NaHC03 solution, brine, and dried (MgS04). The crude product was chromatographed on a flash silica gel column eluting with hexane: EtOAc, 7:3 to give N-(t-butyloxycarbonyl)-pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester. Step C: N-(Pyrrolidin-2(S)-ylmethyl)-3(S)-ethyl-prolyl methionine isopropyl ester hydrochloride N-[(t-Butyloxycarbonyl)-pyrrohdin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine isopropyl ester (1.38 g, 0.0028 mol) was dissolved in EtOAc (40 mL), cooled to -20°C, saturated with HCI gas, and stirred at 0°C. for 1.25 hr, and room temperature for 0.25 hr. Concentration to dryness gave the title compound. Step D: lH-Imidazole-4- acetic acid methyl ester hydrochloride A solution of lH-imidazole-4-acetic acid hydrochloride (4.00g, 24.6 mmol) in methanol (100 ml) was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature (RT) for 18hr. The solvent was evaporated in vacuo to afford the title compound as a white solid. iH NMR(CDCl3, 400 MHz) δ 8.85(1H, s),7.45(lH, s), 3.89(2H, s) and 3.75(3H, s) ppm. Step E: l-(Triphenylmethyl)-lH-imidazol-4-ylacetic acid methyl ester To a solution of lH-Imidazole-4- acetic acid methyl ester hydrochloride (24.85g, O.Hlmol) in dimethyl formamide (DMF) (115ml) was added triethylamine (57.2 ml, 0.412mol) and tribenzyl 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. NaHCθ3 (350 ml), dried (Na2Sθ4) and evaporated in vacuo. The residue was purified by flash chromatography (Siθ2, 0-100% ethyl acetate in hexanes; gradient elution) to provide the title compound as a white solid. i H NMR (CDC13, 400 MHz) δ 7.35( lH, 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 F: [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetic acid methyl ester To a solution of l-(Triphenylmethyl)-lH-imidazol-4- ylacetic acid methyl ester (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 NaHCθ3 (300ml) and CH2CI2 (300ml) and stirred at room temperature for 2 hr. The organic layer was separated, dried (MgS04) and evaporated in vacuo to afford the title compound as a white solid : 1HNMR(CDC13, 400 MHz) δ7.65(lH, 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 G: \ 1 -(4-CvanobenzylV 1 H-imidazol-5-vnacetic 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 lyophilized to afford the title compound containing lithium chloride as a white solid. iH NMR(CD3θD, 400 MHz) δ 8.22(1H, s), 7.74(1H, d, J=8.4Hz), 7.36(1H, d, J=8.4Hz), 7.15(1H, s), 5.43(2H, s) and 3.49(2H, s) ppm. Step H: N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]- pyrτolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl]acetic acid • LiCl (0.416 g. 1.47 mmol). N-(pyrrolidin-2(S)-ylmethyl)-3(S)-ethyl-prolyl- methionine isopropyl ester hydrochloride (Step I) ( 0.63 g, 1.33 mmol), HOOBT (0.239 g, 1.47 mmol), and EDC (0.281 g, 1.47 mmol) were dissolved in degassed DMF (20 mL) with stirring at room temperature, N-methylmorpholine (0.8 mL, 5.32 mmol) was added to achieve a pH of 7, and stirring was continued overnight. The reaction mixture was concentrated to remove most of the DMF, and the residue was partitioned between EtOAc and aq satd NaHCθ3 solution. The aq layer was washed with EtOAc, the organics combined, washed with brine and dried (MgS04). Filtration and concentration to dryness gave the title compound after chromatography on silica gel eluting with CH2C12:CH30H, 95:5. Anal, calcd for C33H46N6O4S • 0.7 H2O: C, 62.38; H, 7.52; N, 13.23; found: C, 62.40; H, 7.17; N, 13.11. FAB MS 623 (M+l) Following the procedures outlined above, but substituting methionine sulfone isopropyl ester for methionine isopropyl ester, the following compound was prepared: N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethvn-3(S -ethyl-prolyl-methionine sulfone isopropyl ester Anal, calcd for C33H46N6O6S • 0.9 H2O: C, 59.07; H, 7.18; N, 12.52; found: C, 58.99; H, 6.87; N, 12.86. FAB MS 655 (M+l) EXAMPLE 3 Preparation of N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5- ylacetyl]pyrτolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine sulfoxide To a solution of N-[ l-[ l -(4-Cyanobenzyl)- lH-imidazol-5- ylacetyl]pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methιonine (0.15 g, 0.186 mM) in 3 mL of MeOH:H2θ 1 : 1 was added sodium periodate (0.048 g, 0.223 mM). The mixture was stirred for 1 h. diluted with 3 mL of H2O and purified by prep HPLC (Delta-pak, C-18). The pure fractions were pooled and lyophillized to yield the title compound. Anal, calcd for C30H40N6O5S • 4.2 CF3CO2H • 0.5 H2O: C, 42.52; H, 4.20; N, 7.75; found: C, 42.51; H, 4.21; N, 8.11. FAB MS 597 (M+l) Following the procedure above the following compound was prepared: N- [ 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyrrolidin-2(S)- vlmethvll-3(S .-ethvl-prolvl-methionine sulfoxide isopropyl ester Anal, calcd for C33H46N6O5S • 1.0 H2O: C, 60.34; H, 7.37; N, 12.80; found: C, 60.32; H, 7.19; N, 12.42. EXAMPLE 4 Preparation of N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5- ylacetvnpyrrolidin-2(SVylmethyll-3(SVethyl-prolyl-methionine sulfone To a solution of N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5- ylacetyl]pyrrolidin-2(S)-ylme_hyl]-3(S)-ethyl-prolyl-methionine (0.15 g, 0.186 mM) in 5 mL of MeOH:H2θ 1: 1 was added Oxone (1.1 g, 0.372 mM). After stirring for 0.5 h, the mixture was partially evaporated and diluted with 5 mL of H2O and purified by prep HPLC (Vydac, C-18). The pure fractions were pooled and lyophilized to yield the title compound. Anal, calcd for C30H40N6O6S • 3.2 CF3CO2H • 1.2 H2O: C, 43.75; H, 4.60; N, 8.41; found: C, 43.75; H, 4.59; N, 8.45. FAB MS 613 (M+l) EXAMPLE 5 Preparation of N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5- ylacetyl]pyιτolicUn-2(S)-ylmemyl]-3(S)-ethyl-prolyl-methioι_ine methyl ester and N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin- 2(SVvlmethvn-3(S.-ethvl-prolyl-methionine Step A: N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]- pyrtolicUn-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester Following the procedures described for Example 2, but substituting methionine methyl ester hydrochloride for methionine isopropyl ester hydrochloride in Step B, the title compound was prepared. Anal, calcd for C31H42N6O4S • 3.7 CF3CO2H • 0.3 H2O: C, 45.13; H, 4.57; N, 8.22; found: C, 45.10; H, 4.53; N, 8.39. Step B: N-[ 1 -[ 1 -(4-Cyanobeιιzyl)- lH-_midazol-5-l)acetyl]pyIτolidin- 2 S ■-ylmethyl^-3 S.-e-hyl-prolyl-methio-^ne trifluoroacetate N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5- ylacetyl]pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester (0.016 g, 0.02 mmol) was dissolved in CH3OH (1 mL) and H2O (1 mL) at ambient temperature and treated with 1 N NaOH (0.3 mL, 0.3 mmol) with stirring. After 1 hr the reaction mixture was neutralized with IN HCI (0.3 mL) and purified on a VYDAC preparative RP HPLC column and lyophilized to give the title compound. Anal, calcd for C30H4ON6O4S • 3.9 CF3CO2H • 0.6 H2O: C, 43.81 ; H, 4.39; N, 8.11; found: C, 43.79; H, 4.39; N, 8.27. Following the procedures outlined in Examples 2 and 3, but substituting the appropriate carboxylic acid in Example 2. Step H; the following compounds were prepared: N-ri-(lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S-)ylmethvn-3(S .-ethyl- prolyl-methionine methyl ester iH NMR (CD3OD) δ 8.88 (s, IH), 7.43 (s, IH), 4.64 - 4.71 (m, IH), 4.19-4.27 (m, IH), 3.94 (s, 2H), 3.75 - 3.88 (m, 2H), 3.74 (s, 3H), 3.57 - 3.61 (m, 2H), 3.34 - 3.5 (m, 3H), 3.15 - 3.25 (m, IH), 2.45 - 2.67 (m, 2H), 1.98 - 2.37 (m, 6H), 2.08 (s, 3H), 1.83 - 1.98 (m, 3H), 1.4 - 1.56 (m, IH), 1.01 (t, 3H, J = 7 Hz). Anal, calcd for C23H37N5O4S • 2.8 CF3CO2H • 1.3 H2O: C, 41.88; H, 4.96; N, 8.54; Found: C, 41.85; H, 4.95; N, 8.54. FAB MS 480 (M + l). N-ri-(lH-Imidazol-4-vlacetvlVpvrrolidin-2(SVvlmethvn-3(SVethyl- prolvl-methionine iH NMR (CD3OD) δ 8.87 (s, IH), 7.43 (s, IH), 4.61 - 4.71 (m, IH), 4.2-4.3 (m, IH), 3.94 (brs, 2H), 3.75 - 3.88 (m, 2H), 3.6 - 3.73 (m, IH), 3.16 - 3.48 (m, 5H), 2.5 - 2.7 (m, 2H), 2.0 - 2.38 (m, 6H), 2.10 (s, 3H), 1.83 - 1.98 (m, 3H), 1.4 - 1.55 (m, IH), 1.01 (t, 3H, J = 7 Hz). Anal, calcd for C22H35N5O4S • 2.8 CF3CO2H: C, 42.24; H, 4.85; N, 8.92; Found: C, 42.18; H, 4.86; N, 8.95. FAB MS 466 (M + l). N-ri-Glycyl-pyrrolidin-2(S)-ylmethyll-3(SVethyl-prolyl-methionine methyl ester FAB MS 429 (M + l). N-π-Glvcyl-pyrrolidin-2(S)-ylmethyll-3(S)-ethyl-prolyl-methionine Anal, calcd for C19H34N4O4S • 3.0 CF3CO2H • 0.5 H2O: C, 39.22; H, 5.00; N, 7.32; Found: C. 39.21 : H, 5.02; N, 7.68. FAB MS 415 (M + 1 ). N-ri-(3-riH-Imidazol-4-vnpropionvlVpyrrolidin-2(S- ylmethyll-3(SV ethyl-prolyl-methionine methyl ester Anal, calcd for C24H39N5O4S • 0.75 H2O: C, 56.84; H, 8.05; N, 13.81; Found: C, 56.79; H, 7.95; N, 13.90. FAB MS 494 (M + l). N-ri-(3-riH-Imidazol-4-vnpropionyl)-pyrrolidin-2(S- ylmethvn-3(S)- ethyl-prolyl-methionine FAB MS 480(M + 1). N-ri-r3-(l-(4-CvanobenzvlVlH-imidazol-5-vnpropionvl1pvrrolidin-2(S)- vlmemvl1-3(S .-ethvl-prolyl-methionine methyl ester Anal, calcd for C32H44N6O4S • 2.0 HCI • 0.4 H2O: C, 55.79; H, 6.85; N, 12.20; Found: C, 55.86; H, 6.85; N, 11.95. FAB MS 609 (M + l). N-ri-r3-(l-(4-Cvanobenzvπ-lH-imidazol-5-vπpropionyllpyιτolidin-2(S .- ylmethvπ-3(S .-ethyl-prolyl-methionine Anal, calcd for C31H42N6O4S • 2.9 CF3CO2H • 0.8 H2O: C, 47.03; H, 4.99; N, 8.94; Found: C, 47.05; H, 4.96; N, 9.31. FAB MS 595 (M + l). EXAMPLE 6 Preparation of N-[2(S)-(lH-Imidazol-4-ylacetyl-amino)-3(S)- methylpentyl]-prolyl-methionine methyl ester and N-[2(S)-(1H- Imidazol-4-ylacetyl-amino -3(S)-methylpentyll-prolyl-methionine Step A: N-[2(S)-( 1 H-Imidazol-4-ylacetyl-amino)-3(S)- ethylpentyll-prolyl-methionine methyl ester Following the methods outlined in Example 1, but substituting N-(t-Butyloxycarbonyl)-isoleucinal for N-[(t- Butyloxy)carbonyl]-3(S)-ethyl-2(S)-prolinal in Step I, the title compound was prepared. Anal, calcd for C22H37N5O4S • 0.5 H2O: C, 55.43; H, 8.04; N, 14.69; Found: C, 55.75; H, 7.82; N, 14.36. FAB MS 468 (M + 1). Step B: N-[2(S)-(lH-Imidazol-4-ylacetyl-amino)-3(S)- methylpentvll-prolvl-methionine The title compound was prepared following the method dscribed in Example 1, Step N. Anal, calcd for C21H35N5O4S • 2.5 CF3CO2H: C, 42.27; H, 5.12; N, 9.48; Found: C, 41.91; H, 5.17; N, 9.51. FAB MS 454 (M + l). EXAMPLE 7 Preparation of N-[l-(lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- prolyl-methionine methyl ester and N-[l-(lH-Imidazol-4-ylacetyl)- pyrrolidin-2(S.-ylmethyll-prolyl-methionine Step A: N-[ 1 -( 1 H-Imidazol-4-ylacetyl)-py_τolidin-2(S)-ylmethyl]- prolyl-methionine methyl ester Following the methods outlined in Example 1 , but substituting N-(t-Butyloxycarbonyl)-prolinal for N-[(t- Butyloxy)carbonyl]-3(S)-ethyl-2(S)-prolinal in Step I, the title compound was prepared. Anal, calcd for C21H33N504S - 1.9 CF3CO2H • 2.2 HCI: C. 39.80; H, 5.00; N, 9.36; Found: C, 39.82; H, 5.01 ; N, 9.33. FAB MS 452 (M + 1 ). Step B: N-[ 1 -( lH-Imidazol-4-ylacetyl)-pyrrohdin-2(S)-ylmethyl]- prolyl-methionine The title compound was prepared following the method dscribed in Example 1, Step N. Anal, calcd for C20H31N5O4S • 2.6 CF3CO2H • 1.1 HCI: C, 40.15; H, 4.79; N, 9.29; Found: C, 40.15; H, 4.85; N, 9.02. FAB MS 438 (M + l). Following the procedures outlined in Examples 1, 2, and 7, the following compounds were prepared: N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- vlmethvn-prolvl-methionine methvl ester Anal, calcd for C29H38N6O4S • 1.2 H2O: C, 59.20; H, 6.92; N, 14.28; Found: C, 59.25; H, 6.81; N, 14.14. FAB MS 567 (M + 1). N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyll-prolyl-methionine Anal, calcd for C28H36N6O4S • 3.4 CF3CO2H • 1.0 H2O: C, 43.61 ; H, 4.35; N, 8.77; Found: C, 43.59; H, 4.35; N, 8.91. FAB MS 553 (M + 1). EXAMPLE 8 Using the procedures described in Example 1 , but substituting 3(S)-Ethyl- 2(S)-proline hydrochloride for proline methyl ester in Step I, the following compounds were prepared: N-[ l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]- £S ethyl-prolyl-methionine methyl ester Anal, calcd for C25H41 N5O4S • 0.5 H2O: C. 50.93: H. 7.52; N. 1 1.88; Found: C. 50..90: H, 7.38; N. 1 1.87. N-[ 1 -(lH-Imidazol-4-vlacetvl)-3(S)-ethvlpvrrolidin-2(S)-vlmethvll-3(SV ethyl-prolyl-methionine trifluoroacetate Anal, calcd for C24H39N5O4S • 2.95 CF3CO2H: C, 43.27; H, 5.09; N, 8.44; Found: C, 43.17; H, 5.16; N, 8.54. N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]-3(S)-ethylpyrrolidin- 2(S .-ylmethyl ■-3(Syethyl-prolyl-methionine methyl ester Anal, calcd for C33H46N6O4S: C, 63.63; H, 7.45; N, 13.50; Found: C, 63.53; H, 7.36; N, 13.39. N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]-3(S)-ethylpyrrolidin- 2(S)-vlmethvπ-3(S -ethvl-prolvl-methionine trifluoroacetate Anal, calcd for C32H44N6O4S • 3.2 CF3CO2H • 0.6 H2θ: C, 46.85; H, 4.96; N, 8.54; Found: C, 46.86; H, 4.96; N, 8.78. N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]-3(S)-ethylpyrrolidin- 2(S)-ylmethyll-3(S)-ethyl-prolyl-methiQnine isopropyl ester Anal, calcd for C35H50N6O4S • 0.25 H2O: C, 64.14; H, 7.77; N, 12.82; Found: C, 64.16; H, 7.73; N, 12.82. N-[l-(3-[lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyll-3(SVethyl-prolyl-methionine methyl ester FAB MS 522 (M + l). N-[ 1 -(3-[ 1 H-Imidazol-4-yl_propionyl)-3(S)-ethylpyπOlidin-2(S)- ylmethyl1-3(S .-ethyl-prolyl-methionine trifluoroacetate FAB MS 508 (M + 1 ). N-[ l-Glycyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine methyl ester N-[l-Glycyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine trifluoroacetate EXAMPLE 9 Preparation of N-[l-(l-(4-Nitrobenzyl)-lH-imidazol-4- ylacetyl]pyrtolidin-2(S)-ylmemyl]-3(S)-ethyl-prolyl-metWonine bis trifluoroacetate and N-[l-(l-(4-Nitrobenzyl)-lH-imidazol-5-ylacetyl] pyrtoli_Un-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine bis trifluoroacetate. Step A: 1 -(4-Nitrobenzyl)- 1 H-imidazol-4-ylacetic acid methyl ester and l-(4-Nitrobenzvl)-lH-imidazol-5-ylacetic acid methyl ester (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 (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. *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), 5.18 ( 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: 1 -(4-Nitrobenzyl)- l H-imidazol-4-ylacetic acid hydrochloride and 1 -(4-Nitrobenzyl)- l H-imidazol-5-ylacetic acid (3: 1 mixture) To a solution of a mixture of 1 -(4-Nitrobenzyl)- 1H- imidazol-4-ylacetic acid methyl ester and 1 -(4-Nitrobenzyl)- 1H- imidazol-5-ylacetic acid methyl ester (3:1 mixture, 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 and the mixture evaporated in vacuo to give the title compounds. iH 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. Step C: N-[ 1 -( 1 -(4-Nitrobenzyl)- 1 H-imidazol-4-ylacetyl]pyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester bis trifluoroacetate and N-[l-(l -(4-Nitrobenzyl)- lH-imidazol-5- ylacetyl]pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl methionine methvl ester bis trifluoroacetate To a solution of l-(4-nitrobenzyl)-lH-imidazol-4-ylacetic acid hydrochloride and l-(4-nitrobenzyl)-lH-imidazol-5-ylacetic acid hydrochloride (3:1 mixture, 0.392 mmol), N-[pyrrolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl methionine methyl ester hydrochloride (0.392 mmol), prepared as described in Example 1, Steps A-L (but utilizing the substitutions described in Example 2, Step A), and 3-hydroxy- 1,2,3- benzotriazin-4(3H)-one (HOOBT, 0.39 mmol) in methylene chloride (10 ml) are added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 0.392 mmol) and triethylamine (1.57 mmol) and the mixture is stirred overnight at room temperature. After this time, sat. aq. sodium bicarbonate (10 ml) is added and the mixture is extracted with methylene chloride. The combined extracts are washed with sat. aq. sodium bicarbonate (10 ml) and the solvent evaporated in vacuo. The regioisomers are separated by preparative HPLC using a Nova Prep 5000 Semi preparative HPLC system and a Waters PrepPak cartridge (47X300mm, C18, 15μm, 100 A) eluting with 5-95% acetonitrile/water (0.1 % TFA) at 100 ml/min (chromatography method A) to give the title compounds after lyophilization. Step D: N- [ 1 -( 1 -(4-Nitrobenzyl)- 1 H-imidazol-4-ylacetyl]pyrroUdin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine bis ttifluQroacetøte To a solution of N- [ 1 -( 1 -(4-nitrobenzy 1)- 1 H-imidazol-4- ylacetyl]pyrroUdin-2(S)-ylmethyl]-3(S)-ethyl-prolyl methionine methyl ester bis trifluoroacetate (0.023 mmol) in methanol (1 ml ) at room temperature is added l.ON lithium hydroxide (135 μl, 0.135 mmol). This solution is stirred for 4 h and treated with trifluoroacetic acid (100 μl). This mixture is purified by preparative HPLC using chromatography method A to give the title compound. Step E: N- [ 1 -( 1 -(4-Nitrobenzyl)- 1 H-imidazol-5-ylace tyljpyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine bis trifluoroacetate To a solution of N-[l-(l-(4-nitrobenzyl)-lH-imidazol-5- ylacetyl]pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl methionine methyl ester bis trifluoroacetate (0.031 mmol) in methanol (1 ml ) is added l.ON lithium hydroxide (187 μl, 0.187 mmol ). This solution is stirred for 4 h and treated with trifluoroacetic acid (100 μl). This mixture is purified by preparative HPLC using chromatography method A to give the title compound. EXAMPLE 10 Preparation of N-[ 1 -( 1 -( 1 -Famesyl)- 1 H-imidazol-5-ylacetyl)-pyrrolidin- 2(S .-ylmethyl 1-3(S .-ethyl-prolyl methionine bis trifluoroacetate Step A: l -( l-Farnesyl .-l H-imidazol-5-ylacetic acid methyl ester To a solution of l -(tribenzyl)- lH-imidazol-4-ylacetic 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. iH 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: N-[ 1 -( 1 -( 1 -Famesyl)- 1 H-imidazol-5-ylacetyl)pyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl methionine methyl ester bis trifluoroacetate Following the procedure described in Example 9, Steps C-D, but using 1 -famesyl- 1 H-imidazol-5-ylacetic acid methyl ester described in Step A in place of l-(4-n_ttobenzyl)-lH-imidazol-5-ylacetic acid methyl ester provides the title compound. Step C: N-[ 1 -( 1 -( 1 -Famesyl)- 1 H-imidazol-5-ylacetyl)pyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl methionine bis trifluoroacetate Following the procedure described in Example 1 , Step N, but using the methyl ester prepared as described in Step B provides the title compound. EXAMPLE 1 1 Preparation of N-[ 1 -( 1 -( 1 -Geranyl)- 1 H-imidazol-5-ylacetyl)-pyrrolidin- 2(S)-ylmethyl ■-3(S .-ethyl-prolyl-rnethionine bis trifluoroacetate Step A: N-[ 1 -( 1 -( 1 -Geranyl )- 1 H-imidazol-5-ylacetyl)pyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 10, Steps A- B, but using trans-geranyl bromide in place of famesyl bromide provides the title compound. Step B: N-[ 1-(1-(1 -Geranyl)- lH-imidazol-5- ylacetyl)py olidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine bis trifluoroacetate Following the procedure described in Example 1, Step N, but using the methyl ester prepared as described in Step A provides the title compound. EXAMPLE 12 Preparation of N-[l-(l-(4-Methoxybenzyl)-lH-imidazol-5- ylacetyl)pyrtolicUn-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine bis trifluoroacetate Step A: N-[ 1 -( 1 -(4-Methoxybenzyl)- 1 H-imidazol-5- yl)acetyl)pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine methyl ester bis trifluoroacetate Following the procedure described in Example 9, Steps B-D, but using 4-methoxybenzyl chloride in place of 4-nitrobenzylbromide provides the tide compound. Step B: N-[l-(l -(4-Methoxybenzyl)- lH-imidazol-5- ylacetyl)py olidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine bis trifluoroacetate Following the procedure described in Example 1 , Step N, but substituting the methyl ester from Step A provides the title compound. EXAMPLE 13 Preparation of N-[l-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetyl]pyrrohdin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine bis trifluoroacetate Step A: N-[l-(l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]3(S)- ethylpy_τohdin-2(S)-ylmethyl]-prolyl-methionine methyl ester bis trifluoroacetate Following the procedure described in Example 9, Steps B-D, but using 2-(bromomethyl)naphthylene in place of 4-nitrobenzylbromide provided the title compound. Step B: N-[l-(l-(2-Naphthylmethyl)-lH-imidazol-5- ylacetyl]pyrtθlidin-2(S)-ylmemyl]-3(S)-ethyl-prolyl- methionine bis trifluoroacetate Following the procedure described in Example 1, Step N, but using the methyl ester prepared as described in Step A provided the title compound. EXAMPLE 14 Preparation of N-[l-(lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl-(β-acetylamino.alanine trifluoroacetate Step A: Methyl 2(SVbenzyloxycarbonylamino-3-amino propionate A solution of 2(S)-benzyloxycarbonylamino-3- aminopropionic acid (2.4 g) in methanol at 0° C was saturated with HCI gas. After stirring for 2 h at 20° C the solution was evaporated to obtain the title compound. 1 HNMR (300 MHz, CD3OD ) δ 7.35 (5H, m), 5.13 (2H, s), 4.50 (IH, m), 3.77 (3H, s), 3.45 ( IH. m), 3.22 (IH, m). Step B: Methyl 2(S)-benzyloxycarbonylamino-3-acetylamino- propionate To a solution of methyl 2(S)-benzyloxycarbonylamino-3- amino propionate (2.5 g) in methylene chloride was added pyridine (20 mL) and acetic anhydride (5 mL). After stirring for 2 h the solution was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The ethyl acetate layer was extracted w/ 50 mL each of 2% potassium hydrogen sulfate, saturated sodium bicarbonate, saturated sodium chloride, dried over magnesium sulfate and concentrated in vacuo. Upon evaporation pyridine hydrochloride precipitated and was removed by filtration. The filtrate was evaporated to obtain the title compound. iHNMR (300 MHz, CDC13 ) δ 7.28 (5H, s), 6.14 (IH, s), 5.97 (IH, d), 5.10 (2H, s), 4.41 (IH, m), 3.78 (3H, s), 1.93 (3H, s). Step C: Methvl 2(SVamino-3-acetvlaminopropionate To a solution of methyl 2(S)-benzyloxycarbonylamino-3- acetylamino-propionate (2.2 g ) in ethanohc HCI was added 10% Pd/C ( 0.3 g) under nitrogen atmosphere. Hydrogen was applied to the mixture at 60 psi for 16 h. The mixture was filtered and concentrated in vacuo. The residue was triturated with diethyl ether to obtain the product. iHNMR (300 MHz, CD3OD) δ 4.20 (IH, m), 3.88 (3H, s), 3.82 (IH, m), 3.60 (lH, m), 1.99 (3H, s). Step D: N-[ 1 -( 1 H-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl-(β-acetylamino)alanine methyl ester trifluoroacetate Following the procedures outlined in Examples 1 and 2, but substituting the methyl 2(S)-amino-3-acetylaminopropionate of Step C for methionine methyl ester hydrochloride in Example 1, Step K, the title compound is prepared. Step E: N-[ l -( lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- 3(SVethyl-proly1-(β-acetylamino.alanine trifluoroacetate The title compound is prepared following the method described in Example 1 , Step N. EXAMPLE 15 In vitro inhibition of ras f arnesyl transferase Assays of famesyl-protein transferase. Partially purified bovine FPTase and Ras peptides (Ras-CVLS, Ras-CVIM and RAS- CAIL) were prepared as described by Schaber et al, J. Biol. Chem. 265: 14701-14704 (1990), Pompliano, et al, Biochemistry 37:3800 (1992) and Gibbs et al, PNAS U.S.A. 56:6630-6634 (1989), respectively. Bovine FPTase was assayed in a volume of 100 μl containing 100 mM _V- (2-hydroxy ethyl) piperazine-_V'-(2-ethane sulfonic acid) (HEPES), pH 7.4, 5 m MgCl2, 5 mM dithiothreitol (DTT), 100 mM [3H]-farnesyl diphosphate ([ 3 H]-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 harvester, 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 radioactivity 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 32:5167-5176 (1993). Human FPTase activity was assayed as described above with the exception that 0.1% (w/v) polyethylene glycol 20,000, 10 μM ZnCl 2 and 100 ΠM Ras-CVIM 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. EX AMPLE 16 In vivo ras famesylation assay The cell line used in this assay is a v-ras line derived from either Ratl or NIH3T3 cells, which expressed viral Ha-ras p21. The assay is performed essentially as described in DeClue, J.E. et al, Cancer Research 51:112-111, (1991). Cells in 10 cm dishes at 50-75% confluency are treated with the test compound (final concentration of solvent, methanol or dimethyl sulfoxide, is 0.1%). After 4 hours at 37°C, the cells are labelled in 3 ml methionine-free DMEM supple-meted with 10% regular DMEM, 2% fetal bovine serum and 400 mCi[35S]methionine (1000 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 a , J. Virol. 43:294-304, (1982)). Following a 2 hour antibody incubation at 4°C, 200 ml of a 25% suspension of protein A-Sepharose coated with rabbit anti rat IgG is added for 45 min. The immunoprecipitates are washed four times with IP buffer (20 nM HEPES, pH 7.5/1 mM EDTA/1% Triton X-100.0.5% deoxycholate/0.1%/SDS/0.1 M NaCl) boiled in SDS-PAGE sample buffer and loaded on 13% acrylamide gels. When the dye front reached the bottom, the gel is fixed, soaked in Enlightening, dried and autoradiographed. The intensities of the bands corresponding to famesylated and nonfarnesylated ras proteins are compared to determine the percent inhibition of famesyl transfer to protein. EXAMPLE 17 In vivo growth inhibition assay To determine the biological consequences of FPTase inhibition, the effect of the compounds of the instant invention on the anchorage-independent growth of Ratl cells transformed with either a v- ras, v-raf, or v-mos oncogene is tested. Cells transformed by v-Raf and v-Mos maybe included in the analysis to evaluate the specificity of instant compounds for Ras-induced cell transformation. Rat 1 cells transformed with either v-ras, v-raf, or v-mos are seeded at a density of 1 x 10 4 cells per plate (35 mm in diameter) in a 0.3% top agarose layer in medium A (Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine 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 at 1000 times the final concentration used in the assay). The cells are fed twice weekly with 0.5 ml of medium A contaimng 0.1% methanol or the concentration of the instant compound. Photomicrographs are taken 16 days after the cultures are seeded and comparisons are made.

Claims: WHAT IS CLAIMED IS: 1. A compound which inhibits famesyl-protein transferase having the Formula I: wherein: Rla and R b are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, RlOO-, R n S(0) m -. R 10 C(O)NRl0-, CN, Nθ2, (Rl ) 2 N-C(NRlO)., RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, or RHOC(O)NRl0-, c) Cl-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl^O-, R π S(0) m -, R10C(O)NR10_, CN, (R10)2N-C(NR10)-, RlOC(O)-, RlOOC(O)-, N3, -N(RlO)2, or Rl lθC(0 NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C 1 -C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl. Br, N(R l 0) . N02. R 10 O-. R l l S(0 m -. R I OQONR I O-. CN, (RlO) 2 N-C(NRl )-, RlOc(O)-, Rl oC(O)-, N3, -N(Rl )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- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independentiy selected from: a) hydrogen, b) C l -C6 alkyl unsubstituted or substituted by alkenyl, R 1 OO-, R π S(0) m -, RlOC(0)NRlO-, CN, N3, (R10)2N-C(NR10)-, RlOC(O)-, RIOOC(O)-, -N(RlO)2, or R 10C(0)NR10-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, R n S(0)m-, R 10 C(O)NRl0-, CN, N02, (R 10 )2N- C(NRl )-, RlOC(O)-, RlOOC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C 10 cycloalkyl; 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. - Ill - 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, (RlO) 2 NC(0)-, N02, R 10 O-, Rl lS(0) m -, RlOC(0)NRlO-, CN, (R10) 2 N-C(NR 0)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO)2, RUOC(0)NR 0- and C1-C20 alkyl, d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- C 10 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(CORlO)- ; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl !S(0)m-, Rl0C(O)NRl0-, CN, Nθ2, Rlθ2N-C(NRlO)-, RIO O)-, RlOθC(O)-, N3, -N(RlO)2, or R 10C(0)NR10-, and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, Rl O-, Rl lS(0) m -, Rl0c(O)NH-, CN, H2N- C(NH)-, Rl0C(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl. perfluoroalkyl. F. Cl. Br. R IOO-, R l l S(0)m-. R l°C(O)NR l0-, CN. Nθ2. (RlO)2N-C- (NRlO)-, RlOC(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or RllOC(O)NRl0-, and c) Cl-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, R10C(0)NR10-, CN, (RlO)2N-C(NRl )-, R10C(O)-, RlOθC(O)-, N3, -N(Rl )2, or Rl lOC(O)NRl0- ; RlO is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; RU is independently selected from -C6 alkyl and aryl; A and A^ are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(R10)-, -S(0)2N(RlO)-, -N(RlO)S(0)2-, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicychc ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A J is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A 2 is S(0)m; W is a heterocycle; X, Y and Z are independently H2 or O; or a pharmaceutically acceptable salt thereof. 2. A prodmg of a compound which inhibits famesyl- protein transferase, the prodmg which is illustrated by the formula II: V - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n wherein: R a and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, Rl^O-, R π S(0) m -, Rl0C(O)NRl -, CN, Nθ2, (Rl ) 2 N-C(NRl0)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or R OC(O)NRl0-, c) Ci-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl. alkynyl, Rl^O-, Rl l S(0)m-, R 10C(0)NR 10-. CN. (R 10) 2 N-C(NR10)., RlQC(O)-, Rl°OC(0)-, N3, -N(R lO) 2 , or R* lθC(O)- NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid. b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C1-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, R 10 O-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, RIOOC(O)-, N3, -N(RlO)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- ClO cycloalkyl; or R2 and R3 are combined to form - (CH 2 ) S - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C 1 -C6 alkyl unsubstituted or substituted by alkenyl, R 1 OO-, R n S(0) m -, Rl0C(O)NRl0-, CN, N3, (RlO) 2 N-C(NRlO)., RlOC(O)-, RlOθC(O)-, -N(Rl0)2, or R lθC(O)NR 0-, c) aryl, heterocycle, cycloalkyl, alkenyl, R OO-, R 1 ^(O^-, Rl°C(O)NRl0-, CN. N02, (Rl°)2N- C(NRlO)-, R 10 C(O)-, RlOθC(O)-. N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocyclic and C3-C10 cycloalkyl; R5a and R5b are independendy 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 2 0 alkyl, C 2 -C 2 0 alkenyl, C3-C10 cycloalkyl, aryl or heterocycle group, wherein the substituent is selected from F, Cl, Br, (RlO) 2 NC(0)-, N0 2 , RlOO-, Rl S(0)m-, Rl C(O)NRl0-, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl ) , R11OC(O)NR10- and Cl-C 2 0 alkyl, 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 - (CH 2 )s - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0)m, -NC(O)-, and -N(CORlO)- ; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R l !S(0)m-, Rl0C(O)NRl0-, CN. Nθ2, R 10 2N-C(NRl0)-, RlOC.O)-, RlOθC(O)-, N3. -N(RlO)2, or Rl lQC(O)NRl0-. and c) C1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R OO-, R S(0)m-, Rl°C(0)NH-, CN, H 2 N- C(NH)-, RlOC(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, Rl°0-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, N0 2 , (RlO) 2 N-C- (NR O)-, Rl0c(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0) m -, R 10 C(O)NRl -, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RIOOC(O)-, N3, -N(RlO) 2 , or Rl lOC(0)NRlO-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from -C6 alkyl and aryl; Rl2 _s a) substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C5-C8 cycloalkyl, or substituted or unsubstituted cyclic amine, wherein the substituted alkyl, cycloalkyl or cyclic amine is substituted with 1 or 2 substituents independently selected from: 1) C1-C6 alkyl, 2) aryl, 3) heterocycle, 4) -N(Rl )2, 5) -OR 10, or b) Rl3 is independently selected from hydrogen and Cl-Cβ alkyl; Rl4 is independently selected from C1-C6 alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRl C(O)-, O, -N(RlO)-, -S(O) 2 N(Rl0)-, -N(Rl0)S(O) 2 -, or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicychc ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) Cl-C 2 0 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C -C 2 0 alkenyl, provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if A is a bond, n is 0 and A2 is S(0)n_; W is a heterocycle; X, Y and Z are independently H 2 or O; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; p is 0, 1 , 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 4 or 5; t is 3, 4 or 5; and u is O or l; or a pharmaceutically acceptable salt thereof. 3. A compound which inhibits famesyl-protein transferase having the Formula III: - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, RlOO-, Rl lS(0)πr, R1°C(0)NR10-, CN, Nθ2, (Rl°)2N- C(NRlO)-, Rl c(O)-, RIOOC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, c) C 1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, Rl O-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(R lO)2, or RHOC(O)- NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a naturally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted Cl-C 2 0 alkyl, C 2 -C 0 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(Rl ) 2 , N0 2 , R OO-, R lS(0) m -, R1 C(0)NR10-, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, R OOC(O)-, N3, -N(RlO) 2 , R 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- C 10 cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C 1 -C6 alkyl unsubstimted or substimted by alkenyl, R 1 n O-, R π S(0) m -, Rl0c(O)NRl0-, CN, N3, (RlO) 2 N-C(NRlO)-, Rl C(O)-, Rl0OC(O)-, -N(Rl0)2, or Rl lOC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, R π S(0)m-, R 10 C(O)NRl0-, CN, N0 , (RlO) 2 N- C(NRl0)-, Rl0c(O)-, RlOθC(O)-, N3, -N(R l0)2, or Rl lOC(O)NRl0-, and d) C 1 -Cβ alkyl substituted with an unsubstimted or substituted group selected from aryl, heterocyclic and C3-C 10 cycloalkyl; R6 is independently selected from hydrogen or C 1 -C6 alkyl: R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, Rl C(0)NRlO-, CN, N02, Rl°2N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, N3, -N(Rl ) 2 , or R11OC(O)NR10-, and c) C 1 -C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R lS(0) m -, R 10 C(O)NH-, CN, H 2 N- C(NH)-, Rl C(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R 1 OO-, Rl S(0)m-, R 10 C(O)NRl0-, CN, N0 2 , (RlO) 2 N-C- (NRlO)-, RlOC(O)-, RIOOC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstimted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, R lS(0) m -, R10C(0)NR 0-, CN, (Rl ) N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(Rl0)2, OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl is independently selected from C1-C6 alkyl and aryl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(RlO)-, -S(O)2N(Rl0)-, -N(Rl )S(0)2-. or S(0) m ; Q is a substituted or unsubstituted nitrogen-containing C4-C9 mono or bicyclic ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle; X, Y and Z are independently H2 or O; or a pharmaceutically acceptable salt thereof. 4. A prodmg of a compound which inhibits famesyl- protein transferase, the prodmg which is illustrated by the formula IV: - A 1 (CR" 2 ) n A !S (CR ,β 2 ) n wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, R OO-, R π S(0) m -, R 10 C(O)NRl0-, CN, N02, (Rl°)2N- C(NRlO)-, RlOc(O)-, RlOθC(O)-, N3 . -N(RlO) 2 , or Rl lOC(O)NRl0-, c) C 1-C6 alkyl unsubstituted or substituted by aryl, heterocyclic, cycloalkyl, alkenyl, alkynyl, RlOO-, R π S(0) m -, R 10 C(0)NR10~, CN, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or RHOC(O)- NR10-; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substituted or unsubstituted C 1 -C 2 0 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N(RlO) 2 , Nθ2, RlOO-, R l lS(0) m -, R 0C(0)NR10-, CN, (RlO)2N-C(NRlO)-, RlOC(O)-, RlOOC(O)-, N3, -N(R 10 )2, R 1 lOC(O)NR l0- and C1 -C2O alkyl. and d) C1-C alkyl substituted with an unsubstituted « - substituted group selected from aryl, heterocycle aiid C3- CiO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a, R4b, R7a and R7b are independently selected from: a) hydrogen, b) C l -C6 alkyl unsubstimted or substituted by alkenyl, R 1 °0-, R π S(0) m -, Rl°C(O)NRl0-, CN, N3, (R10)2N-C(NR10)-, Rl C(O)-, RlOθC(O)-, -N(RlO) , or R lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, Rl lS(0) m -, Rl0c(O)NRl0-, CN, N0 2 , (RlO) 2 N- C(NRl )-, Rl0c(O)-, Rl θC(O)-, N3, -N(RlO) , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substi ted with an unsubstimted or substituted group selected from aryl, heterocyclic and C3-C 10 cycloalkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R lOO-. R l lS(0) m -, R l0C(O)NR l0-, CN. N02- R 1°2N-C(NR 10)-, RlOc(O)-, R lOθC(O)-. N3, -N(R l )2. or R 1 l QC(O)NR l0-, and c) C l -C6 alkyl unsubstituted or substituted by aryl, heterocycle, 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 Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, R lS(0)m-, R 10 C(O)NRl0-, CN, N0 2 , (Rl ) 2 N-C- (NRlO)-, RlOc(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstituted or substi ted by perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0) m -, R! C(O)NR10-, CN, (RlO) 2 N-C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , or RllOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; A and A are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, -NRl C(O)-, O, -N(R10)-, -S(0)2N(RlO)-, -N(RlO)S(0)2-, or S(0) m ; Q is a substimted or unsubstituted nitrogen-containing C4-C9 mono or bicyclic ring system, wherein the non-nitrogen containing ring may be a C5-C7 saturated ring; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A is S(0)m; W is a heterocycle; X, Y and Z are independently H2 or O; or a pharmaceutically acceptable salt thereof. 5. The compound according to Claim 1 of the formula I: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; R ib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R ^O-, -N(RlO) or alkenyl, c) C 1-C6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(RlO) 2 ; R2 and R3 are independentiy selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substituted or unsubstituted C l -C 10 alkyl, C 2 -C 10 alkenyl, C3-C10 cycloalkyl, aryl or heterocyclic group, wherein the substituent is selected from F, Cl, Br, N0 2 , RlOO-, Rl lS(0) m -, R!0C(O)NR10-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RIOOC(O)-, N3, -N(RlO) 2 , Rl lOC(O)NRl0- and C1- 0 alkyl, and d) C1-C6 alkyl substituted with an unsubstituted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R° to form a ring such that R4a and R^a are independently selected from: a) hydrogen. b) C l -C6 alkyl unsubstimted or substimted by alkenyl, R 10θ-, R π S(0)m-, Rl°C(O)NRl0-, CN, N3, (R10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, Nθ2, (Rl°)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , or RHOC(O)NRl0-, and d) C1-C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocyclic and C3- ClO cycloalkyl; R4b and R?b are hydrogen; R5a is selected from: a) a side chain of a namrally occurring amino acid, wherein the amino acid is selected from methionine and glutamine, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, and c) substimted or unsubstimted Ci-Cio 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-, R1°C(0)NR10-, (Rl0) 2 NC(O)-, CN, (R10) 2 N-C(NR10)-, RIOC(O)-, RlOθC(O)-, N3, -N(Rl )2, Rl 10C(0)NR10- and C1-C2O alkyl, and d) C 1 -C6 alkyl substituted with an unsubstimted or substituted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R5b is selected from: a) hydrogen, and b) C 1 -C3 alkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, R OO-, R!0C(O)NR10-, CN, NO2, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C1-C6 alkyl substimted by C1-C6 perfluoroalkyl, RlOO-, Rl C(0)NRlO-, (RlO) 2 N-C(NRlO)-, RlOC(O)-, Rl θC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C 2 -C6 alkenyl, C 2 -C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RIOO-, Rl lS(0) m -, R10C(0)NR 0-, CN, N0 2 , (RlO) 2 N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-, and c) C l -C6 alkyl unsubstimted or substituted by C 1 -Cβ perfluoroalkyl, F, Cl, RlOO-, Rl lS(0) m - . R1°C(0)NR10-, CN, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, RIOOC(O)-, -N(Rl )2, or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(R10)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinohnyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H 2 or O; or a pharmaceutically acceptable salt thereof. 6. The compound according to Claim 2 of the formula II: wherein: Rla is independently selected from: hydrogen or Cl-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl^O-, -N(RlO)2 or alkenyl, c) Cl-C6 alkyl unsubstimted or substimted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(RlO) 2 ; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substituted or unsubstituted C l -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 l S(0) m -, R !0C(O)NR 0-, CN, (Rl0)2N-C(NRl0)-, RlOc(O)-, R IOOC(O)-, N3, -N(R l O 2. R l lOC(O)NR l0- and C 1 -C20 alkyl. and d) C1-C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocycle and C3- Cio cycloalkyl; or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R6 to form a ring such that R4a and R?a are independently selected from: a) hydrogen, b) C 1 -Cβ alkyl unsubstimted or substimted by alkenyl, R °0-, R π S(0) m -, R 10 C(O)NRl0-, CN, N3, (R10)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, R u S(0) m -, R 10 C(O)NRl0-, CN, NO2, (Rl°)2N- C(NRl )-, Rl0c(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocyclic and C3- C 10 cycloalkyl; R4b and R7b are hydrogen; 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 namrally occurring amino acid which is: i) methionine sulfoxide. or ii) methionine sulfone, and c) substimted or unsubstimted 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, R 10 O-, Rl lS(0)m-, R1°C(0)NR10-, (RlO)2NC(0)-, CN, (Rl )2N-C(NRlO)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO)2, R11OC(O)NR1 - and Cl-C 2 0 alkyl, and d) C 1 -C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocycle and C3- ClO cycloalkyl; R5b is selected from: a) hydrogen, and b) C1-C3 alkyl; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2 Cβ alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR10-, CN, N02, (RlO) 2 N-C(NRlO)., Rl c(O)-, RlOθC(O)-, -N(Rl )2, or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl substimted by C 1 -C6 perfluoroalkyl, R 1 °0-, Rl0C(O)NRl0-, (RlO) N-C(NRlO)-, RlOc(O)-, Rl θC(O)-, -N(RlO)2, or Rl 1OC(O)NR10 R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C l -Cβ perfluoroalkyl, F, Cl, RlOO-. R lS(0)m-, R 10 C(O)NRl0-, CN, Nθ2, (Rl°)2N- C(NRl0)-, Rl0C(O)-, R lOθC(O)-. -N(Rl ) 2 , or R 1 10C(0)NR 1 °-, and c) C l -C6 alkyl unsubstimted or substimted by C l -C6 perfluoroalkyl, F, Cl, RlOO-, Rl !S(0) m -, R 10 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOoC(O)-, -N(Rl ) 2 , or Rl lOC(O)NRl0-; RlO is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; Rl2 is a) substimted or unsubstimted Ci-C8 alkyl or substimted or unsubstimted C5-C8 cycloalkyl, wherein the substituent on the alkyl or cycloalkyl is selected from: 1) aryl, 2) heterocycle, 3) -N(Rll) 2 , 4) -ORlO, or b) R 13 O Rl3 is independently selected from hydrogen and C1-C6 alkyl; Rl is independently selected from C1-C6 alkyl; Q is selected from: A! and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(0)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrohdinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H 2 or O; or the pharmaceutically acceptable salts thereof. 7. The compound according to Claim 3 of the formula III: - A 1 (CR 1a 2 ) n A 2 (CR la 2 ) n wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl^O-, -N(Rl0)2 or alkenyl, c) C1-C6 alkyl unsubstimted or substimted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(RlO)2; R2 and R3 are independently selected from: a) a side chain of a namrally occurring amino acid, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) methionine sulfone, c) substimted or unsubstituted C 1 -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, (Rl0) 2 N-C(NRl0)-, RlOC(O)-, RlOθC(O)-, N3, -N(R 10)2, R l ! OC(0)NR 10- and C l -C20 alkyl, and d) C 1-C6 alkyl substituted with an unsubstimted or substituted group selected from aryl, heterocycle and C3- C 10 cycloalkyl: or R2 and R3 are combined to form - (CH2)s - ; or R2 or R3 are combined with R^ to form a ring such that R4a and R^a are independently selected from: a) hydrogen, b) C l -Cβ alkyl unsubstimted or substimted by alkenyl, R 0 O-, Rl lS(0) m -, Rl0C(O)NRl0-, CN, N3, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(Rl )2, or Rl lθC(O)NRl0-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, RllS(0) m -, R 10 C(O)NRl0-, CN, NO2, (R 1( Ϊ)2N- C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocyclic and C3- ClO cycloalkyl; R4b and R 7 b are hydrogen; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C 1 -Cβ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, RlOO-, R10C(0)NR10-, CN, NO2, (Rl0) 2 N-C(NRl0)-, RlOc.O)-, R lOoC(O)-, -N(RlO) 2 , or Rl lOC(O)NRl0-. and c) C l -C6 alkyl substimted by C l -C6 perfluoroalkyl, R 0θ-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RlOθC(O)-, -N(Rl ) 2 , or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C 2 -C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, RIOO-, Rl lS(0)πr. R1°C(0)NR10-, CN, N02, (R 10 )2N- C(NRlO)-, Rl0c(O)-, RlOθC(O)-, -N(RlO) , or RllOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstimted or substimted by C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R lS(0) m -, R i0 C(O)NRl0-, CN, (RlO) 2 N-C(NRlO)-, RlOc(O)-, RIOOC(O)-, -N(Rl ) 2 , OΓ RHOC(O)NR10-; RlO is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from Cl-C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(0)-, -C(O)NRl0-, O, -N(RlO)-. or S(0) m ; V is selected from: a) hydrogen. b) heterocycle selected from pyrrohdinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A is S(0)m; W is a heterocycle selected from pyrrohdinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independently H or O; or a pharmaceutically acceptable salt thereof. 8. The compound according to Claim 4 of the formula Formula IV: wherein: Rla is independently selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R ^O-, -N(RlO) 2 or alkenyl, c) Cl-C6 alkyl unsubstimted or substimted by aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, or -N(RlO) 2 ; R2 and R3 are independently selected from: a) a side chain of a naturally occurring amino acid, b) an oxidized form of a side chain of a namrally occurring amino acid which is: i) methionine sulfoxide, or ii) med ionine sulfone, c) substimted 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, R OO-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, (R lO) 2 N-C(NRlO)-, RlOC(O)-, R OOC(O)-, N3, -N(R lO)2, R 1 !OC(O)NRl0- and C l-C 2 0 alkyl, and d) C1-C6 alkyl substituted with an unsubstimted or substituted group selected from aryl, heterocycle and C3- C lO cycloalkyl; or R2 and R3 are combined to form - (CH 2 )s - ; or R2 or R3 are combined with R6 to form a ring such that R4a and R^a are independently selected from: a) hydrogen, b) C l -C6 alkyl unsubstimted or substimted by alkenyl, R 10θ-, Rl lS(0) m -, R10C(0)NR10-, CN, N3, (R1°) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(RlO) 2 , or R 10C(0)NR10-, c) aryl, heterocycle, cycloalkyl, alkenyl, Rl^O-, R lS(0) m -, Rl°C(O)NRl0-, CN, N0 2 , (Rl ) 2 N- C(NRlO)-, Rl c(O)-, Rl θC(O)-, N3, -N(RlO) 2 , or Rl lOC(O)NRl0-, and d) C1-C6 alkyl substimted with an unsubstimted or substimted group selected from aryl, heterocyclic and C3- C 10 cycloalkyl; R4b and R 7b are hydrogen; R6 is independently selected from hydrogen or C1-C6 alkyl; R8 is independently selected from: a) hydrogen, b) C 1 -Cβ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -Cβ perfluoroalkyl, F, Cl, RlOO-, R 10C(0)NR 10-, CN, NO2, (RlO)2N-C(NRlO)-, R lOc(O)-, R lOOC(O)-, -N(Rl0)2, or Rl lOC(O)NR l0-, and c) C l -C6 alkyl substituted by C 1 -C6 perfluoroalkyl, R 1 °0-, RlOC(0)NRl -, (R10) 2 N-C(NR10)-, RlOc(O)-, RlOθC(O)-, -N(RlO)2, or RHOC(O)NR10- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C 1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)m-, R 10 C(O)NRl0-, CN, Nθ2, (R 10 )2N- C(NRl )-, RlOc(O)-, RlOθC(O)-, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) C 1 -C6 alkyl unsubstimted or substimted by C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, Rl lS(0) m -, R 10 C(O)NRl0-, CN, (RlO)2N-C(NRlO)-, Rl C(O)-, RlOOC(O)-, -N(RlO)2, OΓ RHOC(O)NR10-; R O is independently selected from hydrogen, Cl-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from Cl-C6 alkyl and aryl; Q is selected from: Al and A2 are independently selected from: a bond, -CH=CH-, -C=C-, -C(O , -C(O)NRl0-, o, -N(R lO)-. or S(0) m ; V is selected from: a) hydrogen. b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if A 1 is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A2 is S(0) m ; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X, Y and Z are independenUy H2 or O; or a pharmaceutically acceptable salt thereof. 9. A compound which inhibits famesyl-protein transferase which is: N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]- prolyl-methionine methyl ester N-[ l-( lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]- prolyl-methionine N-[ l-[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfone isopropyl ester N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3 (S)-ethyl-prolyl-methionine sulfoxide N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine sulfoxide isopropyl ester N- [ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3 (S )-ethyl-prolyl-methionine sulfone N-[ 1 -[ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[l-[l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-(lH-lmidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine methyl ester N-[l-(lH-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine N- [ 1 -Glycyl-pyrrolidin-2(S )-ylmethyl]-3 (S )-ethy 1-prolyl-methionine methyl ester N-[l-Glycyl-pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ l-(3-[lH-Imidazol-4-yl]propionyl)-pyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester N-[ 1 -(3-[ 1 H-Imidazol-4-yl]propionyl )-pyrrolidin-2(S )-ylmethyl]-3(S )- ethyl-prolyl-methionine N-[ 1 - [3-( 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl)propionyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[ 1 -[3-( 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl)propionyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[2(S)-(lH-Imidazol-4-ylacetyl-amino)-3(S)-methylpentyl]-prolyl- methionine methyl ester N-[2(S)-(lH-Irnicl_ιzol-4-ylacetyl-amino)-3(S)-methylpentyl]-prolyl- methionine N-[l-(lH-Imidazol-4-ylacetyl)-py_τolidin-2(S-)ylmethyl]-prolyl- methionine methyl ester N- [ 1 -( 1 H-Imidazol-4-ylacetyl)-pyrrolidin-2(S-)ylmethyl]-prolyl- methionine N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-prolyl-methionine methyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-_midazol-5-ylacetyl]pyrrolidin-2(S)- ylmethylj-prolyl-methionine N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester N-[l-(lH-Imidazol-4-ylacetyl)-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine N-[l-[ l -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]-3(S)-ethylpyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[ 1 -[ 1 -(4-Cyanobenzyl )- 1 H-imidazol-5-ylacetyl]-3(S)-ethylpyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine N- [ 1 - [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5 -ylacetyl]-3 (S )-ethy lpyrrolidin- 2(S)-ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester N-[l-(3-[lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester N-[l-(3-[lH-Imidazol-4-yl]propionyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[l-Glycyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)-ethyl-prolyl- methionine methyl ester N-[l-Glycyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-3(S)-eUιyl-prolyl- methionine N-[ l-[ 1 -(4-Nitrobenzyl)- 1 H-imidazol-4-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ 1 -[ 1 -(4-Nitrobenzyl)- 1 H-imidazol-5-ylacetyl] pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ 1 -( 1 -( 1 -Famesyl)- lH-imidazol-5-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- 3(S)-ethyl-prolyl methionine N-[ 1 -( 1 -( 1 -Geranyl)- 1 H-imidazol-5-ylacetyl)-pyrrolidin-2(S)-ylmethyl]- 3 (S )-ethy 1-proly 1-methionine N-[l-[l-(4-Methoxybenzyl)-lH-imid__zol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine N-[ l-[ l-(2-Naphthylmethyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine or N-[ l-( l H-Imidazol-4-ylacetyl)-pyrrolidin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-(β-acetylamino)alanine or a pharmaceutically acceptable salt thereof. 10. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[ 1 -( 1 H-Imidazol-4-ylacetyl)-pyrrohdin-2(S)-ylmethyl]-3(S)-ethyl- prolyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 11. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[(lH-Imidazol-4-ylacetyl-2(S)-amino)-3(S)-methylpentyl]-prolyl- methionine methyl ester or a pharmaceutically acceptable salt thereof. 12. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[l-(3-[lH-Ij__idazol-4-yl]propionyl)-pyrrohdin-2(S)-ylmethyl]-3(S)- ethyl-prolyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 13. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[ 1 -(3-[ 1 H-Imidazol-4-yl]propionyl)-3(S)-ethylpyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine methyl ester or a pharmaceutically acceptable salt thereof. 14. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-y lacetyl]py_τolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine or a pharmaceutically acceptable salt thereof. 15. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[l-[l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- y Imethyl] - 3 (S )-ethy 1-proly 1-methionine methyl ester or a pharmaceutically acceptable salt thereof. 16. The compound according to Claim 9 which inhibits famesyl-protein transferase which is: N-[ 1 -[ 1 -(4-Cyanobenzyl)- lH-imidazol-5-ylacetyl]pyrrolidin-2(S)- ylmethyl]-3(S)-ethyl-prolyl-methionine isopropyl ester 17. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 2. 18. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 4. 19. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 9. 20. 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 17. 21. 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 18. 22. 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 19. 23. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17. 24. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 25. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 19. 26. A method for treating neurofibromin benign proliferative disorder which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17. 27. A method for treating blindness related to retinal vascularization which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17. 28. A method for treating infections from hepatitis delta and related vimses which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17. 29. A method for preventing restenosis which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17. 30. A method for treating polycystic kidney disease which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 17.

Inventors: DESOLMS S JANE, DESOLMS, S., JANE
Applicants: DESOLMS S JANE, MERCK & CO INC, DESOLMS, S., JANE, MERCK & CO., INC.
Application year: 1996
Main classification: C07K
IPC codes: A61K38, A61P9, A61P13, A61P15, A61P27, A61P29, A61P31, A61P35, A61P43, C07K5