INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Description: TITLE OF THE INVENTION INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE 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 conformational change. The GTP-bound form of Ras propagates the growth stimulatory signal until the signal is termiria.t.kl 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-røs, Ki4a-ras, Ki4b-ras and N-ras) are found in marry- 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 involveφ ιth Ras membrane localization, and all 3 modifications occur at the C-terminus of Ras. The Ras C-terminus contains a sequence motif termed a "CAAX" or "Cys-Aaa^-Aaa^-Xaa" box (Cys is cysteine, Aaa is an aliphatic amino acid, the Xaa is any amino acid) (Willumsen et al, Nature 57(9:583-586 (1984)). Depending on the specific sequence, this motif serves as a signal sequence for the enzymes farnesyl-protein transferase or geranylgeranyl-protein transferase, which catalyze the alkylation of the cysteine residue of the CAAX motif with a C 15 or C20 isoprenoid, respectively. (S. Clarke., Ann. Rev. Biochem. 67:355-386 (1992); W.R. Schafer and J. Rine, Ann. Rev. Genetics 50:209-237 (1992)). The Ras protein is one of several proteins that are known to undergo post-translational famesylation. Other farnesylated proteins include the Ras-related GTP-binding proteins such as Rho, fungal mating factors, the nuclear lamins, and the gamma subunit of transducin. James, et al., J. Biol. Chem. 269, 14182 (1994) have identified a peroxisome associated protein Pxf which is also farnesylated. James, et al., have also suggested that there are farnesylated proteins of unknown structure and function in addition to those listed above. Inhibition of farnesyl-protein transferase has been shown to block the growth of Ras-transformed cells in soft agar and to modify other aspects of their transformed phenotype. It has also been demonstrated that certain inhibitors of farnesyl-protein transferase selectively block the processing of the Ras oncoprotein intracellularly (N.E. Kohl et al, Science, 260: 1934-1937 (1993) and G.L. James et al, Science, 260: 1937-1942 (1993). Recently, it has been shown that an inhibitor of farnesyl-protein transferase blocks the growth of ras- dependent tumors in nude mice (N.E. Kohl et al, Proc. Natl. Acad. Sci U.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 farnesyl-protein transferase in vivo has been demonstrated with lovastatin (Merck & Co., Rahway, NJ) and compactin (Hancock et al, ibid; Casey et al, ibid; Schafer et al, Science 245:319 (1989)). These drugs inhibit HMG-CoA reductase, the rate limiting enzyme for the production of polyisoprenoids including farnesyl pyrophosphate. Farnesyl-protein transferase utilizes farnesyl pyrophosphate to covalently modify the Cys thiol group of the Ras CAAX box with a farnesyl group (Reiss et al, Cell, 62:81-88 (1990); Schaber et al, J. Biol Chem., 265: 14701 - 14704 (1990); Schafer et al, Science, 249: 1 133- 1139 (1990); Manne et al, Proc. Natl Acad. Sci USA, 37:7541 -7545 (1990)). Inhibition of farnesyl pyrophosphate biosynthesis by inhibiting HMG-CoA reductase blocks Ras membrane localization in cultured cells. However, direct inhibition of farnesyl- protein transferase would be more specific and attended by fewer side effects than would occur with the required dose of a general inhibitor of isoprene biosynthesis. Inhibitors of farnesyl-protein transferase (FPTase) have been described in two general classes. The first are analogs of farnesyl diphosphate (FPP), while the second class of inhibitors is related to the protein substrates (e.g., Ras) for the enzyme. The peptide derived inhibitors that have been described are generally cysteine containing molecules that are related to the CAAX motif that is the signal for protein prenylation. (Schaber et al, ibid; Reiss et. al, ibid; Reiss et al, PNAS, 55:732-736 (1991)). Such inhibitors may inhibit protein prenylation while serving as alternate substrates for the farnesyl-protein transferase enzyme, or may be purely competitive inhibitors (U.S. Patent 5,141,851, University of Texas; N.E. Kohl et al, Science, 260: 1934-1937 (1993); Graham, et al., J. Med. Chem., 37, 725 (1994)). In general, deletion of the thiol from a CAAX derivative has been shown to dramatically reduce the inhibitory potency of the compound. However, the thiol group potentially places limitations on the therapeutic application of FPTase inhibitors with respect to pharmacokinetics, pharmacodynamics and toxicity. Therefore, a functional replacement for the thiol is desirable. It has recently been reported that farnesyl-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- 112930). It has recently been disclosed that certain tricyclic compounds which optionally incorporate a piperidine moiety are inhibitors of FPTase (WO 95/10514, WO 95/10515 and WO 95/10516). Imidazole-containing inhibitors of farnesyl protein transferase have also been disclosed (WO 95/09001 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 farnesyl-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 piperidine-containing compounds which inhibit the farnesyl-protein transferase. The instant compounds lack a thiol moiety and thus offer unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production. The compounds of this invention are illustrated by the formula A: (CR 1c 2 ) v -Z B DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention are useful in the inhibition of farnesyl-protein transferase and the famesylation of the oncogene protein Ras. In a first embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula A: A wherein: Rla and R lb are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, RΪ0θ~, RΪ lS(0) m -, Rl0C(O)NRΪ0., (R 10) 2 N- C(O)-, CN, Nθ2, (R 1 0) 2 N-C(NRl )_, R10 C (O)-, N3, -N(RlO)2, or R 1 lθC(O)NRl0-, c) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted Ci -Cfj alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R i OO-, R π S(0) m -, Rl0c(O)NRl0-, (R10)2N-C(0)-, CN, (Rl0) 2 N-C(NRl0)-, Rl0c(O)-, N3, -N(RlO)2, and RUOC(O)-NR10- ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R^O-, R U S(0) m -, RlOC(0)NRlO-, (R10) 2 N-C(O)-, CN, (R!0) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, and Rl 1 OC(O)-NR10-, and c) unsubstituted or substituted aryl; R2 and R^ are independently selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, OR 10, O O wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Cl-4 alkyl, h) SR6a, S(0)R6a, Sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR6, 4) SR 6 a, S(0)R6a, or Sθ2R 6a , 5) — NR 6 R 7 R2 and R3 are attached to the same C atom and are combined to form (CH2)u - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0) m , -NC(O)-, and -N(CORI O)- ; R4 and R^ are independently selected from H and CH3; and any two of R2, R , R4 an< j R5 are optionally attached to the same carbon atom; R6, R7 and R^a are independently selected from: H; Cl -4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) unsubstituted aryl, substituted aryl, unsubstituted heteroaryl or substituted heterocycle, c) halogen, d) HO, 1 e) o f) —SO 2 R 11 or g) N(Rl ) 2 ; or R6 and R^ may be joined in a ring; R7 and R^ a may be joined in a ring; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, perfluoroalkyl, F, Cl, Br, R I OQ-, Rl lS(0) m -, Rl0C(O)NRl0. f (RlO) 2 NC(0)-, R 10 2N-C(NRlO)-, CN, Nθ2, R 10 C(O)-, N3, -N(RiO) 2 , or Rl 1OC(O)NR 10-, an c) CJ -C6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C] 0 cycloalkyl, C2-C alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, RlOo-, R n S(0)m-, Rl0c(O)NH-, (Rl0)2NC(O)-, RI O2N- C(NRlO)-, CN, RlOc(O)-, N3, -N(RlO)2, or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, RlOo, Rl lS(0)m-, R 1 0 C(O)NRl0-, (Rl0) 2 NC(O)-, R 10 2 N-C(NR10)-, CN, N02, R 10 C(O)-, N3, -N(RlO)2, or RHθC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, R 10 C(O)NRl0-, (Rl0)2NC(O)-, Rl0 2 N-C(NRlO)-, CN, Rlθc(θ)-, N3, -N(Rl0)2, or Rl lθC(O)NRl0- ; RlO is independently selected from hydrogen, C ] -Cl4 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; R 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; R 2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, substituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl -4 alkyl, b) (CH2)pOR6 d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Ci-4 alkyl, h) SR6a, S(0)R6a, Sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR6, 4) SR6a, S(0)R6a, 0 r Sθ2R 6a , — O-. . NR 6 R 7 8) Y O 9) — O^ / OR 6 T O 11) — S0 2 - NR 6 R 7 \ 12) — N-S0 2 ~ R 6a - U - Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRIOC(O)-, O, -N(R10)-, -S(0) N(RlO)-, -N(Rl0)S(O)2-, or S(0) m ; 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 heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A^ is S(0)m; W is a heterocycle; X is a bond, -CH2-, -C(=0)-, -NR6c(=0)- or -S(=0) m -; χl is a bond, -C(=0)-, -NR6c(=0)-, -NR6-, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOo-, Rl l S(0)m-, R10C(O)NR10-, (R10) 2 N-C(0)-, CN, N02, (R 10 )2N-C(NRl )-, R12C(0)-, RI OOC(O)-, N3, F, -N(RlO) 2 , or Rl lOC(O)NRl0-, and c) unsubstituted or substituted C 1 -C6 alkyl wherein the substitutent on the substituted C1 -C alkyl is selected from unsubstituted or substituted aryl, R!0O-, Rl C(O)NRl0-, (RlO) 2 N-C(0)-, RlOC(O)- and Rl QC(O)-; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1 ; t is 0 or 1 ; u is 4 or 5; and v is 0, 1 or 2; or a pharmaceutically acceptable salt thereof. In a second embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula B: - A 1 (CR 1 a 2 ) n A 2 (CR 1a 2 ) n B wherein: Rla and R b are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C] 0 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, Rl o-, Rl lS(0) m -, R1 C(O)NR 10-, (RlO) 2 N- C(O)-, CN, N02, (Rl°)2N-C(NRlO)-, Rl0c(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) unsubstituted or substituted C 1 -C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 1 Oo-, R n S(0) m -, Rl0C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (Rl0) 2 N-C(NRl0)_, R10C(O)-, N3, -N(RlO) 2 , and Rl lθC(O)-NRl0- ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted Cl-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl o-, R U S(0)m-, R 10 C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (Rl ) 2 N-C(NRl )-, RlOc(O)-, RlOθC(O)-, N3, -N(Rl ) 2 , and Rl lθC(O)-NRl0-, and c) unsubstituted or substituted aryl; R2 and R^ are independently selected from: H; unsubstituted or substituted C l-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, ORlO, O O wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-C 1 -4 alkyl, h) SR6a, S(0)R6 sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR 6 , 4) SR 6a , S(0)R°a, or Sθ2R 6a , 15) N 3 , 16) F, or 17) perfluoro-C 1-4 -alkyl; or R2 and R3 are attached to the same C atom and are combined to form (CH2)u - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0) m , -NC(O)-, and -N(CORl O). ; R4 and R5 are independently selected from H and CH3; and any two of R2, R3, R4 an( j R5 are optionally attached to the same carbon atom; R6, R7 and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) unsubstituted aryl, substituted aryl, unsubstituted heteroaryl or substituted heterocycle, c) halogen, d) HO, e, ) 11 o f) — S0 2 R 11 or g) N(RlO) 2 ; or R6 and R7 may be joined in a ring; R7 and R7 may be joined in a ring; R6 is selected from: C l-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, f) — S0 2 R 11 or g) N(RlO) 2 ; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, perfluoroalkyl, F, Cl, Br, Rl o-, Rl l S(0) m -, R l C(0)NRlO-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, N02, R 10 C(O)-, N3, -N(RlO)2, or RH OC(O)NR 1 -, and c) C 1-C6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, Rl O-, Rl lS(0) m -, Rl 0c(O)NH-, (Rl0) 2 NC(O)-, Rl0 2 N- C(NRl )-, CN, RlOC(O)-, N3, -N(Rl ) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, R Oo-, Rl lS(0)m-, R 10 C(O)NRl0-, (R! 0) 2NC (O)-, R!0 2 N-C(NR10)-, CN, N02, RlOC(O)-, N3, -N(R10) 2 , or RHOC(O)NR10-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOo-, RHS(0)πr, R I 0 C(O)NR l0-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, R l θc(θ)-, N3, -N(RlO)2, OΓ RHOC(O)NR10-; R is independently selected from hydrogen, C]-Cl4 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; R! 1 is independently selected from Cl-C6 alkyl and substituted or unsubstituted aryl; A and A^ are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRIOC(O)-, O, -N(R10)-, -S(0)2N(RlO)-, -N(RlO)S(0)2-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1 -C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, 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 A^ is S(0)m', W is a heterocycle; X 2 is a bond, -CH2-, -C(=0)-, -NR6C(=0)-, -C(=0)NR°-, -NR°-, -O- or -S(=0)m-; Z is an unsubstituted or substituted group selected from aryl and heterocycle, wherein the substituted group is substituted with one or more of the following: 1) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R 6a , or g) -C(0)NR6R7, 2) aryl or heterocycle, or a pharmaceutically acceptable salt thereof. A preferred embodiment of the compounds of this invention is illustrated by the following formula A: wherein: Rl a is independently selected from: hydrogen or C1 -C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(R lO)2 or C2-C6 alkenyl, c) unsubstituted or substituted C1-C alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOo- and -N(R 10)2; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl O-, Rl l S(0) m -, Rl0C(O)NRl0-, (RlO) 2 N-C(0)-, CN, (R10) 2 N-C(NR 10)-, R10C(O)-, RlOθC(O)-, N3, -N(R O)2, and R lOC(O)-NRl0-, and c) unsubstituted or substituted aryl; R3, R4 and R^ are independently selected from H and CH3; NR 6 R 7 and any two of R^, R3, 4 ? anc j R5 are optionally attached to the same carbon atom; R6, R7 and R a are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl -4 alkoxy, b) halogen, or c) aryl or heterocycle; R^a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R8 is independently selected from: a) hydrogen, b) C l -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOO-, R! 0C(O)NR 0-, CN, Nθ2, (RlO)2N-C(NRlO)-, RIOC(O)-, -N(Rl O)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, R OO-, R 1 OC(0)NR 1 -, (R 10) 2 N-C(NR 1 °)-, R 1 °C(0)-, -N(Rl )2, or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, CJ -C6 perfluoroalkyl, F, Cl, RlOo-, Rl lS(0)m-, R10C(O)NR10-, CN, NO2, (Rl0) 2 N-C(NRl0)-, Rl c(O)-, -N(Rl O)2, or R1 1OC(O)NR10-, and c) Cl-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, RlOo-, Rl lS(0) m -, Rl0c(O)NRl0-, CN, (RlO)2N-C(NRlO)-, RlOc(O)-, -N(RlO) 2 , or R1 1OC(O)NR 0- ; RlO is independently selected from hydrogen, C1-C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; R is independently selected from C1-C alkyl and substituted or unsubstituted aryl; Rl2 is selected from: H; unsubstituted or substituted Cl -8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, suvbstituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Cl-4 alkyl, h) SR6a, S(0)R6a S02R 6a 2) C3-6 cycloalkyl, 3) OR6, 4) SR 6 , S(0)R6a, or Sθ2R 6a , A l and A^ are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NR!0-, -NRI OC(O)-, 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, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C 1 -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 is -CH2- or -C(=0)-; Xl is a bond, -C(=0)-, -NR6c(=0)-, -NR6-, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) R OO-, Rl lS(0) m -, R 10 C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, N02, (RlO)2N-C(NRlO)-, Rl2c(0)-, RlOθC(O)-, N3, F, -N(Rl )2, or RHOC(O)NR1 -, and c) unsubstituted or substituted C ] -C6 alkyl wherein the substitutent on the substituted C 1 -C6 alkyl is selected from unsubstituted or substituted aryl, RJOo-, R1 C(O)NR 1 °-, (RlO)2N-C(0)-, RlOC(O)- and Rl OθC(O)-; Z is an unsubstituted or substituted group selected from aryl and heterocycle, wherein the substituted group is substituted with one or more of the following: I) Cl-4 alkyl, unsubstituted or substituted with: a) Cl -4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, g) -C(0)NR6R7, 2) aryl or heterocycle, 3) halogen, 4) OR6, 5) NR6R7, 6) CN, 7) N02, 8) CF3; 9) -S(0) m R6a, 10) -C(0)NR6R7, or I I ) C3-C6 cycloalkyl; or a pharmaceutically acceptable salt thereof. In a another preferred embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula B: B wherein: Rla is independently selected from: hydrogen or C l -C6 alkyl; Ri is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(Rl0)2 or C2-C6 alkenyl, c) unsubstituted or substituted Cl -C6 alkyl wherein the substitutent on the substituted C 1 -C6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, Rl O- and -N(RlO)2; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted Cl-C6 alkyl wherein the substitutent on the substituted Cl-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R Oo-, Rl lS(0)m-, Rl°C(O)NRl0-, (RlO) 2 N-C(0)-, CN, (RlO)2N-C(NRl )-, RlOc(O)-, R l θC(O)-, N3, -N(Rl )2, and Rl lθC(O)-NRl0-, and c) unsubstituted or substituted aryl; R3, R and R are independently selected from H and CH3; \ . NR 6 R 7 T ; R2 is H; O or C 1 -5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR6 4) SR6a, S02R 6a or 5 ) ^ .NR^ 7 T o ; and any two of R , R3, R4 ? a nd R^ are optionally attached to the same carbon atom; R6, R7 and R7 a re independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6 is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, Rl OO-, R10C(O)NR 10-, CN, Nθ2, (RlO)2N-C(NRlO)-, RlOC(O)-, -N(RlO)2, or RHOC(O)NR10-, and c) C1-C6 alkyl substituted by Cl-C6 perfluoroalkyl, Rl°0-, R10C(O)NR10-, (R!0) 2 N-C(NR10)-, R10C(O)-, -N(Rl ) , or Rl lθC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1 -C6 perfluoroalkyl, F, Cl, Rl o-, Rl lS(0) m -, R 1°C(0)NR 10-, CN, NO2, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(Rl )2, or Rl OC(O)NRl0-, and c) C l -C6 alkyl unsubstituted or substituted by C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, RHS(0) m -, R 10 C(O)NRl0-, CN, (Rl )2N-C(NRlO)-, RlOc(O)-, -N(Rl )2, or R1 1OC(O)NR10- ; R lO is independently selected from hydrogen, C1 -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from Cl-C6 alkyl and substituted or unsubstituted aryl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(R O)-, 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 -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 A 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; χ2 is a bond, -CH2-, -C(=0)-, -NR°C(=0)-, -C(=0)NR6-, -NR6-, -O- or -S(=0)mS Z is an unsubstituted or substituted aryl , wherein the substituted aryl is substituted with one or more of the following: 1) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, or a pharmaceutically acceptable salt thereof. A further preferred embodiment of the compounds of this invention are illustrated by the formula C: Z wherein: R a is selected from: hydrogen or C1 -C6 alkyl; Ri is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(R 10)2 or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, or Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, Rl lS(0) m -, Rl°C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (RlO)2N-C(NRlO)-, RlOc(O)-, R lOθC(O)-, N3, -N(RlO)2, and Rl lθC(O)-NRl0-, and c) unsubstituted or substituted aryl; R3 and R independently selected from H and CH3; \ .NR 6 R 7 R 2 is selected from H; ORl°; T O ; or Cl -5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR6, 4) SR6a, Sθ2R 6a , or 5 ) \ . NR 6 R 7 O and R , R3 and R4 are optionally attached to the same carbon atom; R6 and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, Rl O-, R !0C(O)NR 1 -, CN, Nθ2, (RlO) N-C(NRlO)-, RlOc(O)-, -N(RlO)2, or RHOC(O)NR10-, and c) C1-C6 alkyl substituted by C1 -C6 perfluoroalkyl, Rl°θ-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, R10C(O)-, -N(RlO)2, or Rl 0C(0)NR10- ; R^ i s hydrogen or methyl; RI is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; R 2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, substituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) ρerf uoro-Cl-4 alkyl, 2) C3-6 cycloalkyl, 3) OR6 4) SR6a, S(0)R6a, or Sθ2R 6a , 5) — NR 6 R 7 7) N^ / NR 7 R 7a T o O^ . NR 6 R 7 8) T O 9) — O^ / OR 6 T o 11) — SO 2 -NR 6 R 7 13) A o « 14) A OR 6 O 15) N 3 , 16) F, 17) perfluoro-Cι_ 4 -alkyl, or 18) C 1-6 -alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, 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, 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-C2O alkenyl, and provided that V is not hydrogen if A^ is S(0)m and V is not hydrogen if A is a bond, n is 0 and A is S(0) m ; X is -CH2- or -C(=0)-; X I is a bond, -C(=0)-, -NR6c(=0)-, -NR6-, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOO-, Rl lS(0)m-, R !°C(O)NR 10-, (Rl0) 2 N-C(O)-, CN, Nθ2, (RlO)2N-C(NRlO)-, R ! 2C(0)-, RlOθC(O)-, N3, F, -N(Rl )2, or Rl 10C(0)NR10-, c) unsubstituted or substituted C1 -C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, Rl O-, R! 0C(O)NR10-, (RlO)2N-C(0)-, RlOC(O)- and RlOθC(O)-; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1) Cl -4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R6a, or or a pharmaceutically acceptable salt thereof. Another further preferred embodiment of the compounds of this invention are illustrated by the formula D: wherein: Rl a is selected from: hydrogen or C1-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, RlOO-, -N(RlO) 2 or C2-C6 alkenyl, c) Cl-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, Rl OO-, or -N(RlO) 2 ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOo-, Rl lS(0)m-, RlOC(0)NRlO-, (RlO) 2 N-C(0)-, CN, (RlO) 2 N-C(NRlO)-, Rl0c(O)-, RlOθC(O)-, N3, -N(RlO) 2 , and Rl 10C(0)-NR10-, and c) unsubstituted or substituted aryl; R3 and R4 independently selected from H and CH3; NR 6 R 7 R2 is selected from H; OR 10; O G r Ci-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR6 4) SR6a, S02R 6a , or 5 ) \ .NR 6 R 7 O and R , R3 and R4 are optionally attached to the same carbon atom; R6 and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6 is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R is independently selected from: a) hydrogen, b) C l -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -Cβ perfluoroalkyl, F, Cl, Rl O-, R1 C(O)NR 10-, CN, N02, (RlO) 2 N-C(NRlO)-, RlOc(O)-, -N(Rl0)2, or Rl lOC(O)NRl0-, and c) C 1 -Cβ alkyl substituted by C l -C6 perfluoroalkyl, R 1 O-, R!0C(O)NR10-, (RlO) 2 N-C(NRl O)-, R O O)-, -N(RlO)2, or Rl lOC(O)NRl0- ; R^ a is hydrogen or methyl; R O is independently selected from hydrogen, C1-C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; R is independently selected from -C6 alkyl and substituted or unsubstituted aryl; Al and A are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRIOC(O)-, O, -N(R 10)-, 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] -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 A 1 is a bond, n is 0 and A is S(0) m ; χ is a bond, -CH2-, -C(=0)-, -NROC(=0)-, -C(=0)NR6-, -NR6-, -O- or -S(=0) m -; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1) Cj-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, 0 -S(0) m R6a, or g) -C(0)NR6R7, 2) aryl or heterocycle, 3) halogen, 4) OR6, 5) NR6R7, 6) CN, or a pharmaceutically acceptable salt thereof. In another embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula E: wherein: Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl O-, -N(RlO)2 or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOø-, or -N(RlO) 2 ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted Cl-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOo-, R lS(0)m-, Rl0C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (R10) 2 N-C(NR10)-, R10C(O)-, RlOoC(O)-, N3, -N(RlO)2, and RUOC(O)-NR10-, and c) unsubstituted or substituted aryl; R3 and R independently selected from H and CH3; NR 6 R 7 R is selected from H; OR ΪO ; O or Cl-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR6 4) SR6a, Sθ2R 6a or 5 ) \ .NR 6 R 7 0 and R2, R3 and R4 are optionally attached to the same carbon atom; R° R and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6 is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; 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 1 C(O)NR 10-, CN, Nθ2, (Rl ) 2 N-C(NRlO)-, RlOc(O)-, -N(Rl )2, or R1 10C(0)NR 10-, and c) C1-C6 alkyl substituted by C1 -C perfluoroalkyl, RlOo-, Rl0C(O)NRl0-, (R1 ) 2 N-C(NR 0)-, RlOc(O)-, -N(RlO) , or Rl lOC(O)NRl0- ; R O is independently selected from hydrogen, C1 -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; Rl2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, suvbstituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, b) halogen, c) CN, d) perfluoro-C l -4 alkyl, 2) C3-6 cycloalkyl, 3) OR6, 4) SR6a, S(0)Rθ , or Sθ2R 6 χl is a bond, -C(=0)- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOo-, Rl lS(0) m -, R 1°C(0)NR10-, (R 10 )2N-C(O)-, CN, N02, (R )2N-C(NRlO)-, R! 2C(0)-, RlOθC(O)-, N3, F, -N(RlO)2, or Rl lOC(O)NRl0-, c) unsubstituted or substituted C1 -C6 alkyl wherein the substitutent on the substituted C1-C alkyl is selected from unsubstituted or substituted aryl, Rl°0-, R!0C(O)NR ' 0-, (RlO) 2 N-C(0)-, RlOC(O)- and RlOθC(O)-; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1 ) Cl-4 alkyl, unsubstituted or substituted with: a) C]-4 alkoxy, b) NROR7, In another embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula F: wherein: Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, RlOO-, -N(RlO) 2 or C2-C6 alkenyl, c) C1-C alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, or -N(RlO) 2; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, R lS(0) m -, R 1°C(0)NR10-, (Rl0) 2 N-C(O)-, CN, (Rl O) 2 N-C(NRlO)-, Rl Oc(O)-, RlOθC(O)-, N3, -N(R 10) 2 , and R 11 OC(0)-NR 10-, and c) unsubstituted or substituted aryl; R3 and R independently selected from H and CH3; NR 6 R 7 R is selected from H; ORlO; O or C l -5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR6, 4) SRόa Sθ2R 6a , or 5 ) \ ^NR 6 R 7 Y O ; and R , R3 and R4 are optionally attached to the same carbon atom; R6, R7 and R7a are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R 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)NR 0-, CN, N02, (R10) 2 N-C(NR10)-, RlOC(O)-, RlOθC(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0-, and c) C1 -C6 alkyl substituted by C1 -C perfluoroalkyl, R OO-, RlOC(0)NRlO-, (R10) 2 N-C(NR 10)-, RlOC(O)-, RlOθC(O)-, -N(RlO)2, or Rl lOC(0)NRlO-; RlO is independently selected from hydrogen, C j-C l4 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; χ is -CH2-, -C(=0)-, -C(=0)NR6- or -NR°-; or the pharmaceutically acceptable salts thereof. The preferred compounds of this invention are as follows: N-{ [l-(4-Cyanobenzyl)- lH-imidazol-5-ylJmethyl }-4-(3-methylphenyl)- 4-hydroxy piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl }-4-(3-chlorophenyl)-4 hydroxy piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -4-(2- methylbenzyl)isonipecotic acid methyl ester, N-{ tl-(4-Cyanobenzyl)-lH-imidazol-5-yllmethyl }-4-(3-methylphenyl)-4 hydroxy piperidine, N- { [ 1 -(4-Cy anobenzyl)- 1 H-imidazol-5-yl]acety 1 } -4-(2- methylbenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } -4-(4- methylbenzyl))isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y llacetyl } -4-(3- methylbenzyl))isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-yllacetyl } -4-(2,4- dichlorobenzyl))isonipecotic acid methyl ester, N- { L 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acety 1 } -4-(3- methoxybenzyl)isonipecotic acid methyl ester, N- { 11 -(4-Cy anobenzyl)- 1 H-imidazol-5-yllacetyl } -4-( 1 - naphthylmethyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cy anobenzyl)- 1 H-imidazol-5-ylJacety 1 } -4-(4- chlorobenzyl)isonipecotic acid methyl ester, N-{ [ l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl }-4-(2,3- dichlorobenzyl)isonipecotic acid methyl ester, N-{ l-(4 Cyanobenzyl)-lH-imidazol-5-yl-aminocarbonyl }-4-(2- methylbenzyl) isonipecotic acid methyl ester, 2(R,S)-N { -2- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]2-(4- cyanobenzyl) } acetyl-4-(2-methylbenzyl)-isonipecotic acid methyl ester, N- { f 1 -(Naphth-2-ylmethyl)- 1 H-imidazol-5-yl]acetyl }-4-(2- methylbenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -4-methoxymethyl-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzy 1)- 1 H-imidazol-5-yl]acetyl } — 4-methoxymethy 1-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } -4-hydroxymethyl-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]ethyl }-4-(2- methylbenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -trans-4-(3- methylphenyl)-3-hydroxypiperidine, N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl } -trans-4- (3- methylphenyl)-3 methoxy piperidine, N- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -trans-4- (3- methylphenyl)-3 benzyloxy piperidine, l-[2(R,S)-Amino-3-(2-tetradecyloxyphenyl)propylJ-4-(2- methylbenzyl)isonipecotic acid methyl ester, N-2-(S)-aminolauroyl-4-(l-napthylmethyl) isonipecotic acid methyl ester, 4-(Benzoxazolidin-2-one- 1 -yl)- 1 -[ 1 -(4-cyanobenzyl)-5- imidazolylacetyl]piperidine, 4-( 1 ,2-Dihydro-4(H)-3, 1 -benzoxazin-2-one- 1 -yl)- 1 -[ 1 -(4-cyanobenzyl)- 5-imidazolylacetyl]piperidine, 4-(l,2-Dihydro-4(H)-3,l-benzoxazin-2-one-l -yl)- l-[l -(4-cyanobenzyl)- 5-imidazolylmethyl]piperidine, N-[2- { (4-Cyanobenzyl)-5-imidazolyl }ethyl]-4-carbamoyl- 1 - phenylpiperidine 4- [2- { 1 -(4-Cyanobenzyl)-5-imidazolyl } ethyl ] - 1 -phenylpiperidine 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 ylmethyl] imidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5- [4-Hy droxy methy l-4-(3-trifluoromethy lbenzy l)-piperidine- 1 - ylmethyljimidazol- 1 -ylmethyl } benzonitrile 4- { 5- [4-Hy droxy methy l-4-(3-trifluoromethy lbenzy l)-piperidine-l - ylmethyl]-2-methylimidazol- 1 -ylmethyl Jbenzonitrile 4- { 5-[4-Hydroxymethyl-4-(2-trifluoromethylbenzyl)-piperidine- 1 ■ ylmethyljimidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Hydroxymethyl-4-(2-methylbenzyl)piperidine-l - ylmethyl]imidazol-l -ylmethyl jbenzonitrile 4-{5-f4-Hydroxymethyl-4-(3-rnethylbenzyl)piperidine-l- ylmethyljimidazol- 1 -ylmethyl Jbenzonitrile 4-{5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- l -ylmethyl]-2- methylimidazol- 1 -ylmethyl } benzonitrile 4-(5- { 2-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 -yl]-2- oxoethyl } imidazol- 1 -ylmethyl)benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 - carbonyljimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2-methylbenzyl)piperidine- 1 - carbonyllimidazol-1 -ylmethyl} benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-chlorobenzyl)-piperidine- 1 -ylmethyl]- 2-methylimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(2-cyanobenzyl)-piperidine- l-ylmethyl]-2- methylimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-cyanobenzyl)-piperidine-l-ylmethyl]-2- methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(4-cyanobenzyl)piperidine- 1 -ylmethyl]-2- methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2,5-dimethylbenzyl)piperidine- 1 - ylmethyll-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2,5-dichlorobenzyl)piperidine- 1 - ylmethylj-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3,5-dimethylbenzyl)piperidine- 1 ■ ylmethyll-2-methylimidazol-l-ylmethyl }benzonitrile 4-(5-{4-Hydroxymethyl-4-[3,5-bis(trifluoromethyl)benzyl]- piperidine- 1 -ylmethyl }-2-methylimidazol-l-ylmethyl)benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2,3-dichlorobenzyl)piperidine- 1 - ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-[5-(4-Hydroxymethyl-4-benzylpiperidine-l-ylmethyl)-2- methy limidazol- 1 -ylmethyljbenzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine-l ylmethyl]-2-methylimidazol- 1 -ylmethyl }benzamide 4-{ 5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-l- ylmethyl]imidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-l-ylmethyl]- 2-methylimidazol- 1 -ylmethyl }benzonitrile 4-{5-[4-Methoxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine-l - ylmethyl]imidazol- 1 -ylmethyl }benzonitrile 4- { 5-[4-Methoxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 y lmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Methoxymethyl-4-(2-trifluoromethoxybenzyl)-piperidine- 1 - ylmethyljimidazol- 1 -ylmethyl Jbenzonitrile 4-{ 5-[4-Methoxymethyl-4-(2-trifluoromethoxybenzyl)-piρeridine-l- ylmethyl]-2-methy limidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-cyanobenzyl)-piperidine-l -ylmethyl]-2- methy limidazol- 1 -ylmethyl } benzonitrile 4-(5- { 2-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine- 1 -yl]-2- oxoethy 1 } imidazol- 1 -ylmethyl)benzonitrile 4- { 5-[4-Methoxymethyl-4-(3-methylbenzyl)piperidine- 1 - carbonyl] imidazol- 1 -ylmethyl }benzonitrile Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4- (3-trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- cyanobenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-[3- (benzyloxycarbonylaminomethyl)benzyl]piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyI)-3H-imidazol-4-ylmethyl]-4-[3- (aminomethyl)benzyl]piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyI)-2-methyl-3H-imidazol-4-ylmethyl]-4-[3- (methanesulfonylaminomethyl)benzyl]piperidine-4-carboxylate Ethyl H3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-(3- nitrobenzyI)piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-(3- methanesulfonylaminobenzyl)piperidine-4-carboxylate Ethyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- benzylpiperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- cyclopropylmethyIpiperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methylbenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methylbenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- cyanobenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3- methylbenzyl)piperidine-4-carboxylate (±) Methyl 2-(n-butyl)-l-13-(4-cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- methylbenzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3-methyl- benzyl)isonipecotamide l -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethylJ-4-(2- methylbenzyl)piperidine-4-carbonitrile 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(4- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylethylJ-4-(2- methylbenzyl)piperidine-4-carbonitrile 4-{5-f4-Hydroxymethyl-4-(4-methylpyridin-2-ylmethyl)-piperidine- l-ylmethyl]-2-methylimidazol-l -ylmethyl }benzonitrile 4- { 5- [4-Hy droxymethyl-4-(6-methylpyridin-2-y lmethyl)-piperidine- l-ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(2-methylpyridin-4-ylmethyl)-piperidine- l-ylmethyl]-2-methylimidazol-l-ylmethyl }benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(4-chloropyridin-2-ylmethyl)-piperidine- l-ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(6-methylpyridin-2-ylmethyl)-piperidine- 1 -ylmethyljimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(6-hydroxypyridin-2-ylmethyl)- piperidine- l-ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-[5-(4-Hydroxymethyl-4-quinolin-2-ylmethyl-piperidine-l- ylmethyl)-2-methylimidazol- 1 -ylmethyljbenzonitrile Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzoyl)piperidine-4-carboxylate l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzoyl)piperidine l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(hydroxy-m- tolylmethyl)piperidine 4- { 5-[4-Hydroxymethyl-4-(3-tolylsulfanyl)piperidine- 1 - ylmethyl]imidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-tolylsulfanyl)piperidine-l- ylmethyljimidazol- 1 -ylmethyl } benzonitrile 4- { 5- [4-Methoxymethyl-4-(3-tolylsulf inyl)piperidine- 1 ylmethyl] imidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Methoxymethyl-4-(3-tolylsulfonyl)piperidine- 1 - ylmethyl]imidazol- 1 -ylmethyl } benzonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)isonipecotamide Ethyl l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidine-4-carboxylate l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-hydroxymethyl-4- (3-methylphenylamino)piperidine 0-{ l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methyl } carbamate l-13-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylurea l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylsulfamide 4-{5-[4-(Hydroxydiphenylmethyl)piperidin- l -ylmethyl]imidazol-l - ylmethyl } benzonitrile 4- { 5-[4-(Hydroxydiphenylmethyl)piperidine- 1 -carbonyljimidazol- 1 - ylmethyl } benzonitrile 4-(5-{2-[4-(Hydroxydiphenylmethyl)piperidin-l-yl]-2-oxoethyl }-3H- imidazol- 1 -ylmethyl)benzonitrile l-(Piperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole 1 -( 1 -Phenylpiperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole l-(l-(2-Methylphenyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole l-(l-(2-Chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 1 -( 1 -(3-Chlorobenzoyl)piperidin-4-ylmethy l)-5-(4- cyanobenzyl)imidazole 1 -( 1 -(3-Chlorobenzenesulfony l)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 1 -( 1 -(3-Chlorobenzyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 2-[3-(4-Cyanobenzyl)-3H-imidazol-l -yl]-N-(l-phenylpiperidin-4- yl)acetamide 2-[3-(4-Cyanobenzyl)-3H-imidazol-l-yl]-N-benzyl-N-( l - phenylpiperidin-4-yl)acetamide 2-[3-(4-Cyanobenzyl)-3H-imidazol-l-yl]-N-(l -phenylpiperidin-4-yl)- N-pyridin-4-ylmethylacetamide 2-[3-(4-Cyanobenzyl)-3H-imidazol- 1 -yl]-N-phenethyl-N-( 1 - phenylpiperidin-4-yl)acetamide 4-{ 5-[(l-Phenylpiperidin-4-ylamino)methyl]imidazol-l- ylmethyl } benzonitrile 4-(5- { [Benzyl( 1 -phenylpiperidin-4-yl)amino]methyl } imidazol- 1 - ylmethyl)benzonitrile 4-(5- { [( 1 -Phenylpiperidin-4-yl)pyridin-4- ylmethylamino] methyl} imidazol- l-ylmethyl)benzonitrile 4-(5- { [Phenethyl( 1 -phenyIpiperidin-4-yl)arnino]methyl } imidazol- 1 - ylmethyl)benzonitrile 4- { 5- [2-( 1 -Phenylpiperidin-4-ylamino)ethyl]imidazol- 1 - ylmethyl } benzonitrile 4-(5- { 2- [Benzyl( 1 -phenylpiperidin-4-yl)amino]ethyl } imidazol- 1 - ylmethyl)benzonitrile 2-[3-(4-Cyanobenzyl)-3H-imidazol-l-yl]-N-(4-cyanobenzyl)-N-0 - phenylpiperidin-4-yl)acetamide N-(l-Benzylpiperidin-4-yl)-2-[3-(4-cyanobenzyl)-3H-imidazol-4- yl]acetamide and 4- { 5-[( 1 -Benzylpiperidin-4-ylamino)methyl]imidazol- 1 - ylmethyl } benzonitrile or a pharmaceutically acceptable salt thereof. Specific examples of the compounds of the invention are: N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl }-4-(3-methylphenyl)- 4-hydroxy piperidine 4- { 5-f4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 ylmethyljimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-L4-Hydroxymethyl-4-(4-chloropyridin-2-ylmethyl)-piperidine- l ylmethy l]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Methoxymethyl-4-(3-tolylsulfanyl)piperidine-l- ylmethyl]imidazol-l -ylmethyl } benzonitrile trifluoroacetate salt l_[3_(4_Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-hydroxymethyl-4-(3- methy lphenyl amino)piperidine l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethylJ-4-(3- methylphenylamino)-piperidyl-4-methylcarbamate 1 -( 1 -(3-Chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 4- { 5-[( 1 -Benzylpiperidin-4-ylamino)methyl]imidazol- 1 • ylmethyl } benzonitrile or the pharmaceutically acceptable salts thereof. 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. When any variable (e.g. aryl, heterocycle, Rl, R2 etc.) occurs more than one time in any constituent, its definition on each occurence is independent at every other occurence. Also, combinations of substituents/or variables are permissible only if such combinations result in stable compounds. As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms; "alkoxy" represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge. "Halogen" or "halo" as used herein means fluoro, chloro, bromo and iodo. As used herein, "aryl" is intended to mean any stable monocyclic or bicyclic carbon ring of up to 7 members in each ring, wherein at least one ring is aromatic. Examples of such aryl elements include phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl. The term heterocycle or heterocyclic, as used herein, represents a stable 5- to 7-membered monocyclic or stable 8- to 1 1- membered bicyclic heterocyclic ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic elements include, but are not limited to, azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzoxazolidinonyl, benzoxazinonyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, 2-oxopiperazinyl, 2-oxopiperdinyl, 2-oxopyrrolidinyl, piperidyl, piperazinyl, pyridyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, and thienyl. As used herein, "heteroaryl" is intended to mean any stable monocyclic or bicyclic carbon ring of up to 7 members in each ring, wherein at least one ring is aromatic and wherein from one to four carbon atoms are replaced by heteroatoms selected from the group consisting of N, O, and S. Examples of such heterocyclic elements include, but are not limited to, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolyl, naphthyridinyl, oxadiazolyl, pyridyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl. pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, thiazolyl, thienofuryl, thienothienyl, and thienyl. As used herein in the definition of R and R3, the term "the substituted group" intended to mean a substituted Cl-8 alkyl, substituted C2-8 alkenyl, substituted C2-8 alkynyl, substituted aryl or substituted heterocycle from which the substitutent(s) R2 and R3 are selected. As used herein in the definition of R°\ R7 and R7 , the substituted Cl-8 alkyl, substituted C3-6 alkenyl, substituted aroyl, substituted aryl, substituted heteroaroyl, substituted arylsulfonyl, substituted heteroarylsulfonyl and substituted heterocycle include moieties containing from 1 to 3 substitutents in addition to the point of attachment to the rest of the compound. As used herein, when no specific substituents are set forth, the terms "substituted aryl", "substituted heterocycle" and "substituted cycloalkyl" are intended to include the cyclic group which is substituted on a substitutable ring carbon atom with 1 or 2 substitutents selected from the group which includes but is not limited to F, Cl, Br, CF3, NH2, N(Cl-C6 alkyl)2, NO2, CN, (C1 -C6 alkyl)0-, -OH, (C1-C6 alkyl)S(0)m-, (C1-C6 alkyl)C(0)NH-, H2N-C(NH)-, (C] -C6 alkyl)C(O)-, (C1-C6 alkyl)OC(O)-, N3,(Cl-C6 alkyl)OC(0)NH-, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl and C1-C2O alkyl. When R2 and R are combined to form - (CH2)u - » cyclic moieties are formed. Examples of such cyclic moieties include, but are not limited to: In addition, such cyclic moieties may optionally include a heteroatom(s). Examples of such heteroatom-containing cyclic moieties include, but are not limited to: Lines drawn into the ring systems from substituents (such as from R2, R3, R4 e t c ) indicate that the indicated bond may be attached to any of the substitutable ring carbon atoms. Preferably, Rla and Rib are independently selected from: hydrogen, -N(RlO) 2 , Rl c(0)NRlO- or unsubstituted or substituted C 1 -C6 alkyl wherein the substituent on the substituted C l -C alkyl is selected from unsubstituted or substituted phenyl, -N(Rl O) 2 , RlOo- and R ' 0C(O)NR10-. More preferably, Rla and R ϊ b are independently selected from: hydrogen or unsubstituted or substituted C1-C6 alkyl wherein the substituent on the substituted Cl-C6 alkyl is selected from unsubstituted or substituted phenyl, -N(RlO) 2 , RIOØ- and R!OC(0)NR10-. Preferably, R is selected from: H, OR , O O and an unsubstituted or substituted group, the group selected from Cl-8 alkyl, C2-8 alkenyl and C2-8 alkynyl; wherein the substituted group is substituted with one or more of: 1 ) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, 2) C3-6 cycloalkyl, 3) OR6, 4) SR6 , S(0)R6a, Sθ2R 6a , 6 D 7 5) NR°R — O^ / NR 6 R 7 8) T O 9) -O^OR 6 T O 11) — S0 2 -NR 6 R 7 13) O 14 > -AT 0 * 0 15) N 3 , or 16) F. Preferably, R3 is selected from: hydrogen and Cl-C6 alkyl. Preferably, R4 and R^ are hydrogen. Preferably, R6, R7 and R7a is selected from: hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted aryl and unsubstituted or substituted cycloalkyl. Preferably, R6a is unsubstituted or substituted C1 -C6 alkyl, unsubstituted or substituted aryl and unsubstituted or substituted cycloalkyl. Preferably, R 0, is hydrogen or methyl. Most preferably, R9 is hydrogen. Preferably, RlO is selected from H, C1-C6 alkyl and substituted and unsubstituted benzyl. Preferably, Rl2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, suvbstituted aryl or substituted heterocycle is substituted with one or more of: 1 ) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, b) halogen, c) CN, d) perfluoro-Cl-4 alkyl, 2) C3-6 cycloalkyl, 3) OR6, 4) SR6a, S(0)R6a, or Sθ2R 6a Preferably, Al and A2 are independently selected from: a bond, -C(O)NRl0-, -NR10C(O)-, O, -N(R10)-, -S(0)2N(R1 )- and- Preferably, V is selected from hydrogen, heterocycle and aryl. More preferably, V is phenyl. Preferably, χl is a bond. Preferably, X 2 is a bond, -CH2-, -C(=0)-, -NR6C(=0)-, -C(=0)NR6- or -S(=0) m -. Preferably, Y is selected from hydrogen, RlOO-, Rl0C(O)NRl0-, (Rl0) 2 N-C(O)-, R12C(0)-, Rl θC(O)-, -N(Rl ) 2 , and unsubstituted or substituted Cl-C6 alkyl. More preferably, Y is RlOO-, RlOθC(O)- and unsubstituted or substituted Cl-C6 alkyl. Preferably, Z is selected from unsubstituted or substituted phenyl, unsubstituted or substituted naphthyl, unsubstituted or substituted pyridyl, unsubstituted or substituted furanyl and unsubstituted or substituted thienyl. More preferably, Z is unsubstituted or substituted phenyl or unsubstituted or substituted naphthyl. Preferably, W is selected from imidazolinyl, imidazolyl, oxazolyl, pyrazolyl, pyrrolidinyl, thiazolyl and pyridyl. More preferably, W is selected from imidazolyl and pyridyl. Preferably, n and r are independently 0, 1 , or 2. Preferably p is 1 , 2 or 3. Preferably s is 0. Preferably t is 1. Preferably, the moiety is selected from: It is intended that the definition of any substituent or variable (e.g., Rla, R9, n , etc.) at a particular location in a molecule be independent of its definitions elsewhere in that molecule. Thus, -N(RlO)2 represents -NHH, -NHCH3, -NHC2H5, etc. It is understood that substituents and substitution patterns on the compounds of the instant invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art, as well as those methods set forth below, from readily available starting materials. 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, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxy-benzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, trifluoroacetic and the like. The pharmaceutically acceptable salts of the compounds of this invention can be synthesized from the compounds of this invention which contain a basic moiety by conventional chemical methods. Generally, the salts are prepared either 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. Reactions used to generate the compounds of this invention are prepared by employing reactions as shown in the Schemes 1-29, 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. Substituents R a and Rb, as shown in the Schemes, represent the substituents R2, R3 5 R4 ? anc j R5; substituent "sub" represents a suitable substitutent on the substituent Z. The point of attachment of such substituents to a ring is illustrative only and is not meant to be limiting. These reactions may be employed in a linear sequence to provide the compounds of the invention or they may be used to synthesize fragments which are subsequently joined by the alkylation reactions described in the Schemes. Synopsis of Schemes 1-29: The requisite intermediates utilized as starting material in the Schemes hereinbelow are in some cases commercially available, or can be prepared according to literature procedures. In Scheme 1 , for example, a suitably substituted Boc protected isonipecotate I may be deprotonated and then treated with a suitably substituted alkylating group, such as a suitably substituted benzyl bromide, to provide the gem disubstituted intermediate III. Deprotection and reduction provides the hydroxymethyl piperidine IV which can be utilized is synthesis of compounds of the invention or which may be nitrogen-protected and methylated to give the intermediate V. As shown in Scheme 2, the protected piperidine intermediate III can be deprotected and reductively alkylated with aldehydes such as l-trityl-4-imidazolyl-carboxaldehyde or l-trityl-4- imidazolylacetaldehyde, to give products such as VI. The trityl protecting group can be removed from VI to give VII, or alternatively, VI can first be treated with an alkyl halide then subsequently deprotected to give the alkylated imidazole VIII. The deprotected intermediate Ilia can also be reductively alkylated with a variety of other aldehydes, such as IX, as shown in Scheme 3. 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 (Scheme 3). 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 X can be deprotected with trifluoroacetic acid in methylene chloride to give the final compound XI. The final product XI is isolated in the salt form, for example, as a trifluoroacetate, hydrochloride or acetate salt, among others. The product diamine XI can further be selectively protected to obtain XII, which can subsequently be reductively alkylated with a second aldehyde to obtain XIII. Removal of the protecting group, and conversion to cyclized products such as the dihydroimidazole XV can be accomplished by literature procedures. Alternatively, the intermediate Ilia can be acylated or sulfonylated by standard techniques. The imidazole acetic acid XIX can be converted to the acetate XXI by standard procedures shown in Scheme 4, and XXI can be first reacted with an alkyl halide, then treated with refluxing methanol to provide the regiospecifically alkylated imidazole acetic acid ester XXII. Hydrolysis and reaction with piperidine Ilia in the presence of condensing reagents such as 1 -(3- dimethylaminopropyl)-3-ethylcarbodiimide (EDC) leads to acylated products such as XXIV. An alternative synthesis of the hydroxymethyl intermediate IV and utilization of that intermediate in the synthesis of the instant compounds which incorporate the preferred imidazolyl moiety is illustrated in Scheme 4a. Scheme 4b illustrates the reductive alkylation of intermediate IV to provide a 4-cyanobenzylimidazolyl substituted piperidine. The cyano moiety may be selectively oxidized with sodium borate to provide the corresponding amido compound of the instant invention. Scheme 4c alternative preparation of the methyl ether intermediate V and the alkylation of V with a suitably substituted imidazolylmethyl chloride to provide the instant compound. Preparation of the homologous l-(imidazolylethyl)piρeridine is illustrated in Scheme 4d. Specific substitution on the piperidine of the compounds of the instant invention may be accomplished as illustrated in Scheme 4e. Thus, metal-halogen exchange coupling of a butynyl moiety to an isonicotinate, followed by hydrogenation, provides the 2-butylpiperidine intermediate that can then undergo the reactions previously described to provide the compound of the instant invention. Incorporation of a 4-amido moiety for Y is illustrated in Scheme 4f. If the piperidine Ilia is reductively alkylated with an aldehyde which also has a protected hydroxyl group, such as XXV in Scheme 5, the protecting groups can be subsequently removed to unmask the hydroxyl group (Schemes 5, 6). 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 XXIX. In addition, the fully deprotected amino alcohol XXX can be reductively alkylated (under conditions described previously) with a variety of aldehydes to obtain secondary amines, such as XXXI (Scheme 6), or tertiary amines. The Boc protected amino alcohol XXVII can also be utilized to synthesize 2-aziridinylmethylpiperidine such as XXXII (Scheme 7). Treating XXVII with l '-sulfonyldiimidazole and sodium hydride in a solvent such as dimethylformamide led to the formation of aziridine XXXII. The aziridine reacted in the presence of a nucleophile, such as a thiol, in the presence of base to yield the ring-opened product XXXIII. In addition, the piperidine Ilia can be reacted with aldehydes derived from amino acids such as O-alkylated tyrosines, according to standard procedures, as shown in Scheme 8, to obtain compounds such as XXXIX. When R' is an aryl group, XXXIX can first be hydrogenated to unmask the phenol, and the amine group deprotected with acid to produce XL. Alternatively, the amine protecting group in XXXIX can be removed, and O-alkylated phenolic amines such as XLI produced. Scheme 9 illustrates the synthesis of the instant compounds wherein the moiety Z is attached directly to the piperidine ring. Thus the piperidone XLII is treated with a suitably substituted phenyl Grignard reagent to provide the gem disubstituted piperidine XLIII. Deprotection provides the key intermediate XLIV. Intermediate XLIV may be acetylated as described above to provide the instant compound XLV (Scheme 10). As illustrated in Scheme 1 1 , the protected piperidine XLIII may be dehydrated and then hydroborated to provide the 3- hy droxy piperidine XLVI. This compound may be deprotected and further derivatized to provide compounds of the instant invention (as shown in Scheme 12) or the hydroxyl group may be alkylated, as shown in Scheme 11, prior to deprotection and further manipulation. The dehydration product may also be catalytically reduced to provide the des-hydroxy intermediate XL VIII, as shown in Scheme 13, which can be processed via the reactions illustrated in the previous Schemes. Schemes 14 and 15 illustrate further chemical manipulations of the 4-carboxylic acid functionality to provide instant compounds wherein the substituent Y is an acetylamine or sulfonamide moiety. Scheme 16 illustrates incorporation of a nitrile moiety in the 4-position of the piperdine of the compounds of formula A. Thus, the hydroxyl moiety of a suitably substituted 4-hydroxypiperidine is substituted with nitrile to provide intermediate IL, which can undergo reactions previously described in Schemes 1-8. Scheme 17 illustrates the preparation of several pyridyl intermediates that may be utilized with the piperdine intermediates such as compound I in Scheme 1 to provide the instant compounds. Scheme 18 shows a generallized reaction sequence which utilizes such pyridyl intermediates. Compounds of the instant invention wherein χl is a carbonyl moiety may be prepared as shown in Scheme 19. Intermediate L may undergo subsequent reactions as illustrated in Schemes 1-8 to provide the instant compounds. Preparation of the instant compounds wherein χl is sulfur in its various oxidation states is shown in Scheme 20. Intermediates LI-LIV may undergo the previously described reactions to provide the instant compounds. Scheme 21 illustrated preparation of compounds of the formula A wherein Y is hydrogen. Thus, suitably substituted isonipecotic acid may be treated with N,0-dimethylhydroxylamine and the intermediate LV reacted with a suitably substituted phenyl Grignard reagent to provide intermediate LVI. That intermediate may undergo the reactions previously described in Schemes 1-8 and may be further modified by reduction of the phenyl ketone to provide the alcohol LVII. Compounds of the instant invention wherein χl is an amine moiety may be prepared as shown in Scheme 22. Thus the N-protected 4-piperidinone may be reacted with a suitably substituted aniline in the presence of trimethylsilylcyanide to provide the 4-cyano-4- aminopiperidine LVIII. Intermediate LVIII may then be converted in sequence to the corresponding amide LIX, ester LX and alcohol LXI. Intermediates LIX-LXI can be deprotected and can then undergo the reactions previously described in Schemes 1 -8 to provide the compounds of the instant invention. Preparations of compounds of formula B wherein χ2 is an amido or an amine moiety are illustrated in Schemes 23, 24 and 25. As is clear from the reaction illustrated, the intermediate LXIII can undergo any of the piperidine nitrogen reactions illustrated in Schemes 1 -8 to provide the instant compounds. Schemes 26-29 illustrate syntheses of suitably substituted aldehydes useful in the syntheses of the instant compounds wherein the variable W is present as a pyridyl moiety. Similar synthetic strategies for preparing alkanols that incorporate other heterocyclic moieties for variable W are also well known in the art. -76- SCHEME 1 -78 - SCHEME 3 CF CO H CH CIc XI SCHEME 3 (continued) SCHEME 4 XIX xx 1) ArCH 2 X CH 3 CN reflux . 2) CH 3 OH, reflux XXI XXII XXIII SCHEME 4 (continued) XXIII XXIV SCHEME 4a EDC, HOAt SCHEME 4h SCHEME 4c HCl, EtOAc iProNEt SCHEME 4d HCl, EtOAc (CF 3 S0 2 ) 2 0 SCHEME 4e 1. H 2 , Pt 2 0 sub 2. (Boc) 2 0 NaHMDS sub SCHEME 4f SCHEME 5 VIII XXV SCHEME 5 (continued) SCHEME 6 XXVII XXX sub SCHEME 7 XXVII XXXII sub SCHEME 8 XXXIV XXXV XXXVI XXXVII XXXVIII SCHEME 8 (continued) sub SCHEME 9 XLII SCHEME10 SCHEME 11 dine XLIII XLVI XLVI I SCHEME 12 XLVI sub Tr SCHEME 13 ridine XLVIII HOBt DMF su SCHEME 14 Benzyl alcohol 1. Na HMDS EDC, DMAP 2. benzyl bromide SCHEME 14 (continued) Tr SCHEME 15 SCHEME 16 HCl, EtOAc Sub Sub SCHEME 17 SOCI-: SCHEME 17 (continued) SOCIj SCHEMF 1 NaHMDS LiAIH, SCHEME 19 R = CH , CH CH SCHEME 20 LiAIH Oxone SCHEME 21 HCI ' EIOAC Sub SCHEME 22 LIX LiAIH, SCHEME 23 LXIII SCHEME 24 SCHEME 25 yde SCHEME 26 NaBH 4 (excess) SCHEME 27 SCHEME 28 NaBH 4 (excess) SCHEME 29 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 activity (i.e., neurofibromin (NF-1), neu, scr, abl , lck, fyn) or by other mechanisms. The compounds of the instant invention inhibit farnesyl- 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 alFASEB Journal, 2: A3160 (1988)). The instant compounds may also be useful for the treatment of fungal infections. The compounds of this invention may be administered to mammals, preferably humans, either alone or, preferably, in combination with pharmaceutically acceptable carriers or diluents, optionally with known adjuvants, such as alum, in a pharmaceutical composition, according to standard pharmaceutical practice. The compounds can be administered orally or parenterally, including the intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical routes of administration. For oral use of a chemotherapeutic compound according to this invention, the selected compound may be administered, for example, in the form of tablets or capsules, or as an aqueous solution or suspension. In the case of tablets for oral use, carriers which are commonly used include lactose and corn starch, and lubricating agents, such as magnesium stearate, are commonly added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous use, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled in order to render the preparation isotonic. The compounds of the instant invention may also be co- administered with other well known therapeutic agents that are selected for their particular usefulness against the condition that is being treated. For example, the instant compounds may be useful in combination with known anti-cancer and cytotoxic agents. Similarly, the instant compounds may be useful in combination with agents that are effective in the treatment and prevention of NF-1, restinosis, polycystic kidney disease, infections of hepatitis delta and related viruses and fungal infections. If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described below and the other pharmaceutically active agent(s) within its approved dosage range. Compounds of the instant invention may alternatively be used sequentially with known pharmaceutically acceptable agent(s) when a combination formulation is inappropriate. 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 pharmacolo- gically acceptable carriers, e.g., saline, at a pH level, e.g., 7.4. The solutions may be introduced into a patient's blood-stream by local bolus injection. As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients in the specific amounts, as well as any product which results, directly or indirectly, from combination of the specific ingredients in the specified amounts. 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 60 mg/kg of body weight per day, preferably of between 0.5 mg/kg of body weight to about 40 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 farnesyl-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 farnesyl 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 farnesyl-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 farnesyl-protein transferase, an excess amount of a known substrate of FPTase (for example a tetrapeptide having a cysteine at the amine terminus) and farnesyl pyrophosphate are incubated for an appropriate period of time in the presence of varying concentrations of a compound of the instant invention. The concentration of a sufficiently potent inhibitor (i.e., one that has a Ki substantially smaller than the concentration of enzyme in the assay vessel) required to inhibit the enzymatic activity of the sample by 50% is approximately equal to half of the concentration of the enzyme in that particular sample. EXAMPLES Examples provided are intended to assist in a further understanding of the invention. Particular materials employed, species and conditions are intended to be further illustrative of the invention and not limitative of the reasonable scope thereof. EXAMPLE 1 Preparation of N-{ [l-(4-cyanobenzyl)-lH-imidazol-5-yl]methyl}-4-(3- methylphenyl)-4-hydroxy piperidine. Step A: l-Triphenylmethyl-4-(hydroxymethyl)-imidazole. To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35.0 g, 260 mmol) in dry DMF (250 ml) at room temperature was added triethylamine (90.6 ml, 650 mmol). A white solid precipitated from the solution. Chlorotriphenylmethane (76.1 g, 273 mmol) in of DMF (500 ml) was added dropwise. The reaction mixture was stirred for 20 hrs, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid which was sufficiently pure for use in the next step. Step B: l-Triphenylmethyl-4-(acetoxymethyl)-imidazole. The alcohol from Step A (260 mmol, prepared above) was suspended in pyridine (500 ml). Acetic anhydride (74 ml, 780 mmol) was added dropwise, and the reaction was stirred for 48 hrs during which it became homogeneous. The solution was poured into EtOAc, washed sequentially with water, 5% aqueous HCl solution, saturated aqueous NaHCθ3, solution, and brine, the organic extracts were dried (Na2Sθ4), and concentrated in vacuo to provide the product as a white powder, which was sufficiently pure for use in the next reaction. Step C: 1 -(4-Cyanobenzyl)-5-(acetoxymethyl)-imidazole hydrobromide A solution of the product from Step B (85.8 g, 225 mmol) and 4-cyano benzyl bromide (50.1 g, 232 mmol) in EtOAc (500ml) was stirred at 60 °C for 20 hrs, during which a pale yellow precipitate formed. The reaction was cooled to room temperature and filtered to provide the solid imidazolium bromide salt. The filtrate was concentrated in vacuo to a volume (200 ml), reheated at 60 °C for 2 hrs, cooled to room temperature, and filtered again. The filtrate was concentrated in vacuo to a volume (100 m), reheated at 60 °C for another 2hrs, cooled to room temperature, and concentrated in vacuo to provide a pale yellow solid. All of the solid material was combined, dissolved in methanol (500ml), and warmed to 60 °C. After 2hrs, the solution was concentrated in vacuo to provide a white solid which was triturated with hexane to remove soluble materials. Removal of residual solvents in vacuo provided the titled product hydrobromide as a white solid which was used in the next step without further purification. Step D: l -(4-Cyanobenzyl)-5-(hydroxymethyl)-imidazole To a solution of the acetate from Step C (50.4 g, 150 mmol) in 3: 1 THF/water (1.5 1) at 0 °C was added lithium hydroxide monohydrate (18.9 g, 450 mmol). After lhr, the reaction was concentrated in vacuo, diluted with EtOAc (3 1), and washed with water, sat. aq. NaHCθ3 and brine. The solution was then dried (Na2Sθ4), filtered, and concentrated in vacuo to provide the crude product as a pale yellow fluffy solid which was sufficiently pure for use in the next step without further purification. Step E: 1 -(4-Cvanobenzyl -5-imidazole carboxaldehyde. To a solution of the alcohol from Step D (21.5 g, 101 mmol) in DMSO (500ml) at room temperature was added triethylamine (56 ml, 402 mmol), then Sθ3-pyridine complex (40.5 g, 254 mmol). After 45 min, the reaction was poured into EtOAc, washed with water and brine, dried (Na2S04), and concentrated in vacuo to provide the aldehyde as a white powder which was sufficiently pure without further purification. Step F: N-t-Butoxycarbonyl-4- (3-methylphenyl)-4-hydroxy piperidine. To a solution of 3-methylphenyl magnesium bromide (58ml of a IM solution in THF, 58.0 mmol) at 0°C was added a solution of N-t-butoxycarbonyl piperidin-4-one (lO.Og, 53mmol) in THF (30ml) dropwise over 20min, and the reaction stirred under argon for a furthur 30min. The reaction was quenched by addition of sat NH4CI solution (100ml), and diluted with EtOAc. The organic extracts were dried, (MgSθ4) and the solvent evaporated in vacuo to afford the title compound of sufficient purity to be used in the next step. IH NMR CD3OD δ 7.31 (IH, s), 7.28-7.16(2H, m), 7.05(1H, brd, J=7.1Hz), 3.97(2H, d, J=13Hz), 3.40-3.10(2H, m), 2.35(3H, s), 1.94(2H, dt, J=4.4 and 12.7Hz), 1.70(2H, d, J=12.7Hz) and 1.49(9H, s)ppm. Step G: 4-(3-Methylphenyl)-4-hydroxypiperidine hydrochloride. To a solution of N-t-butoxycarbonyl-4-(3-methylphenyl)-4- hydroxy piperidine (0.546mg, 1.87mmol) in EtOAc (30ml) at 0°C was bubbled gasseous HCl until saturated. After 10 min the solvent was evaporated in vacuo to afford the title compound of sufficient purity to be used in the next step. lH NMR CD3OD δ 7.33 (IH, s), 7.32-7.16(2H, m), 7.10(1H, brd, J=7.0Hz), 3.44(2H, t, J=14Hz), 3.40-3.20(2H, m), 2.36(3H, s), 2.24(2H, dt, J=4.4 and 13.5Hz) and 1.92(2H, d, J=13.5Hz)ppm. Step H: N-{[l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl}-4-(3- methylphenyl)-4 hydroxy piperidine. To a mixture of 4-(3-methylphenyl)-4-hydroxypiperidine hydrochloride (457mg, 2.00mmol), the aldehyde from step E (508mg, 2.41 mmol), and 3 A molecular sieves (2.0 g) in methanol (20 ml) was added sodium cyanoborohydride (2.20 ml of a I M solution in THF, 2.20 mmol). The pH was adjusted to 5 by addition of acetic acid and the reaction stirred under argon for 48hrs at room temperature. The solids were removed by filtration and the filtrate partitioned between EtOAc and saturated NaHCθ3 solution, the organic extracts were dried (MgSθ4), and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, gradient elution, 5 to 7% MeOH in methylene chloride. The residue was converted to the corresponding hydrochloride salt by its treatment with a solution of two equivalents of HCl in aqueous acetonitrile and subsequent evaporation of solvents in vacuo. Anal. Calcd for C24H26N4O-2.0HC1-0.95H2O: C, 60.49; H, 6.32; N, 11.76. Found: C, 60.32; H, 6.42; N, 11.95. FAB HRMS exact mass calcd for C24H27N4O: 387.218487 (MH+); found 387.218317. IH NMR CD3OD δ 9.00 (IH, s), 8.09 (IH, s), 7.84 (2H, d, J=8.4Hz), 7.56 (2H, d, J=8.4Hz), 7.35 (IH, s), 7.30 (IH, d, J=7.7Hz), 7.24 (IH, t, J=7.4Hz), 7.10 (lH,d, J=7.4Hz), 5.82 (2H, s), 4.56 (2H, s), 3.65-3.45 (4H, m), 2.52 (2H, m), 2.35 (3H, s) and 1.94 (2H, d, J=14.4Hz) ppm. EXAMPLE 2 Preparation of N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y llmethyl } -4-(3- chlorophenyl -4 hvdroxy piperidine. The title compound was prepared according to the procedure in Example 1, Steps F-H replacing 3-methylphenyl magnesium bromide with 3-chlorophenyl magnesium bromide. Anal. Calcd for C23H23N4OC1-2.0HC1-0.35H2O-0.20CH3CN: C, 56.85; H, 5.36; N, 11.90. Found: C, 56.83; H, 5.38; N, 11.89. FAB MS 407 (MH+). NMR δ CD3OD 9.02 (IH, s), 8.15 (IH, s), 7.84 (2H, d, J=8.0Hz), 7.60 (2H, d, J=8.0Hz), 7.59 (IH, s), 7.45 (IH, d, J=7.7Hz), 7.36 (IH, t, J=7.0Hz), 7.29 (IH, d, J=7.7Hz), 5.87 (2H, s), 4.58 (2H, s), 3.65-3.45 (4H, m), 2.59 (2H, m) and 1.94 (2H, d, J=14.3Hz) ppm. EXAMPLE 3 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl }-4-(2- methylbenzyPisonipecotic acid methyl ester. Step A: N-t-Butoxycarbonyl isonipecotic acid. To a solution of isonipecotic acid (25.8 g, 200 mmol) in 1 M aqueous NaOH (223 ml, 223 mmol) was added a solution of di-t-butyl dicarbonate in THF (200 ml) over 1 hr. The resulting solution was stirred at room temperature for 16hrs. The reaction mixture was then concentrated in vacuo to remove the THF and the residual aqueous solution extracted with hexane . The hexane extracts were combined and back extracted with saturated NaHCθ3. All of the basic aqueous solutions were combined and cooled to 0°C and then acidified with a 15% aqueous KHSO4 solution to a pH of 1-2. The resulting thick slurry was extracted with EtOAc (4x), combined and washed with brine, dried (MgS04) and concentrated in vacuo to afford the product as a white solid. Step B: N-t-Butoxycarbonyl isonipecotic acid methyl ester To an ice cold solution of N-t-butoxycarbonyl isonipecotic acid (8.8 g, 34.9 mmol), in a 10% mixture of methanol in benzene (250 ml), was added a 2.0 M solution of trimethylsilyldiazomethane in hexanes, dropwise, until a consistent yellow color was obtained (-30 ml). After vigorous gas evolution had ceased, the reaction mixture was stirred for 1 hr at room temperature. The mixture was then treated dropwise with glacial acetic acid until the yellow color had dissipated. The reaction was stirred 15 min. and concentrated in vacuo to a pale yellow oil. The residue was purified by chromatography (Si02,eluting with 20% EtOAc in hexanes). Evaporation of the solvent in vacuo afforded the product as a colorless oil. Step C: N-t-Butoxycarbonyl-4-(2-methylbenzyl)-isonipecotic acid methyl ester To a solution of N-t-butoxycarbonyl isonipecotic acid methyl ester (lO.lg 41.8 mmol) in 140 ml of dry THF at -78°C was added LDA (59 ml of a 1.0 M solution in THF , 59 mmol) over 15 min. The resulting orange solution was stirred at -78°C for 1 hr and then treated dropwise with 2-methylbenzyl bromide (6.80 ml, 50.7 mmol) and then allowed to warm slowly to room temperature over 16 hrs. The reaction was quenched with saturated aqueous NH4CI, diluted with H2O, and extracted with EtOAc. The combined organic extracts were washed with brine , and concentrated in vacuo to an orange gum. Chromatography (Si02, eluting with 20 to 30% EtOAc in hexanes) and evaporation of solvent in vacuo, afforded the product as a white solid. Step D: 4-(2-Methylbenzyl)-isonipecotic acid methyl ester hydrochloride salt. To a solution of N-t-butoxycarbonyl-4-(2-methylbenzyl)- isonipecotic acid methyl ester (7.13g, 20.5mmol) in EtOAc (100 ml) at 0°C. was bubbled HCl gas until saturated. The reaction was stirred for lOmin at 0°C and the solvent evaporated in vacuo to afford the product as a white solid. IH NMR CD3OD, δ 7.25-7.00(4H, m), 3.70(3H, s), 3.30(2H, m), 2.98(2H, s), 2.85(2H, dt, J=2.5 and 13.5Hz), 2.36(2H, d, J=15.0Hz), 2.29(3H, s) and 1.76(2H, m)ppm. Step E: N- { [ 1 -(4-Cy anobenzyl)- 1 H-imidazol-5-y ljmethy 1 } -4-(2- methylbenzyPisonipecotic acid methyl ester. The title compound was prepared using the procedure from example 1 step H and the hydrochloride salt from Step D. FAB HRMS exact mass calcd for C27H31N4O2 443.244702(MH+); found 443.245590. Anal. Calcd for C27H30N4θ2*2.95TFA: 0.35H2O: C, 50.32 H, 4.32; N, 7.14. Found: C, 50.30; H, 4.28; N, 7.10. EXAMPLE 4 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl }-4-(3- methylphenyl)-4 hvdroxy piperidine. Step A: 1 H-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 for 18 hrs. The solvent was evaporated in vacuo to afford the title compound as a white solid. IH NMR CDC13, δ 8.85(1H, s), 7.45(1H, s), 3.89(2H, s) and 3.75(3H, s) ppm. Step B: 1 -(Triphenylmethyl)- 1 H-imidazol-4-y lacetic acid methyl ester. To a solution of the product from Step A (24.85g, 0.141mol) in DMF (115ml) was added triethylamine (57.2 ml, 0.412mol) and triphenylmethyl bromide (55.3g, 0.171mol) and the suspension was stirred for 24 hrs. After this time, the reaction mixture was diluted with EtOAc and water. The organic phase was washed with saturated aqueous NaHCθ3, dried (Na2Sθ4) and the solvent evaporated in vacuo. The residue was purified by chromatography (Siθ2, gradient elution, 0-100% EtOAc in hexanes; ) to provide the title compound as a white solid. IH NMR CDCI3, δ 7.35(1H, s), 7.31(9H, m), 7.22(6H, m), 6.76(1H, s), 3.68(3H, s) and 3.60(2H, s) ppm. Step C: [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetic acid methyl ester. To a solution of the product from Step B (8.00g, 20.9mmol) in acetonitrile (70 ml) was added 4-cyanobenzyl bromide (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 was collected by filtration. The filtrate was heated at 55 °C for 18hrs. The reaction mixture was cooled to room temperature and evaporated in vacuo. To the residue was added EtOAc (70 ml) and the resulting precipitate collected by filtration. The precipitated imidazolium salts were combined, suspended in methanol ( 100 ml) and heated to reflux for 30 min. 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 with EtOAc. The solid was treated with saturated aqueous NaHCθ3 solution (300ml) and CH2CI2 (300ml) and stirred at room temperature for 2 hrs. The organic layer was separated, dried (MgSθ4) and evaporated in vacuo to afford the title compound as a white solid IHNMR CDCI3, δ 7.65(1H, d, J=8Hz), 7.53(1H, s), 7.15(1H, d, J=8Hz), 7.04(1H, s), 5.24(2H, s), 3.62(3H, s) and 3.45(2H, s) ppm. Step D: ri -(4-Cyanobenzyl)-lH-imidazol-5-yllacetic acid. A solution of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid methyl ester (4.44g, 17.4mmol ) in THF (100ml) and 1 M lithium hydroxide (17.4 ml, 17.4 mmol) was stirred at room temperature for 18 hrs. 1 M HCl (17.4 ml) was added and the THF removed by evaporation in vacuo. The aqueous solution was lyophilised to afford the title compound containing lithium chloride as a white solid. IH NMR CD3OD, δ 8.22(1H, s), 7.74(1H, d, J=8.4Hz), 7.36(1H, d, J=8.4Hz), 7.15(1H, s), 5.43(2H, s) and 3.49(2H, s) ppm. Step E: N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y llacety 1 } -4-(3- methylphenyl)-4 hvdroxy piperidine. To a mixture of the piperidine hydrochloride from example I step G (102mg, 0.447mmol), [1 -(4-cy anobenzyl)- 1 H-imidazol-5- yljacetic acid (from step D) (127mg, 0.447mmol), HOOBT (73mg, 0.447mmol) and triethylamine (0.187ml, 1.34mmol) in DMF (3ml)was added EDC (86mg, 0.447mmol) and the reaction stirred at room temperature for 18 hrs. The reaction was diluted with EtOAc and washed with saturated NaHCθ3 solution. The organic extracts were dried (Na2Sθ4) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (C-l 8, gradient elution, 95:5 to 5:95 water: acetonitrile containing 0.1 % trifluoroacetic acid). Lyophilization afforded the title compound as a white powder. Anal. Calcd for C25H26N4O2-1.60 TFA: 0.65H2O: C, 55.65 H, 4.79; N, 9.21. Found: C, 55.68 H, 4.79; N, 8.98. FAB HRMS exact mass calcd for C25H27N402: 415.213401 (MH+); found 415.212530. iH NMR CD3OD δ 8.95 (IH, d, 1.4Hz), 7.78 (2H, d, J=8.5Hz), 7.53 (IH, s), 7.49 (2H, d, J=8.5Hz), 7.27 (IH, s), 7.30-7.20 (2H, m), 7.07 (IH, d, J=7.0Hz), 5.53 (2H, s), 4.34 (IH, d, J-l l.OHz), 3.95 (2H, s), 3.76 (IH, d, J=11.0Hz),3.50 (IH, dt, J=2.3 and 12.5Hz), 3.13 (IH, dt, J=2.7 and 12.5Hz), 2.35 (3H, s) and 2.10-1.60 (4H, m) ppm. EXAMPLE 5 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl}-4-(2- methylbenzyPisonipecotic acid methyl ester. The title compound was prepared using the procedure from example 4 step E substituting 4-(2-methylbenzyl)-isoniρecotic acid methyl ester for 4-(3-methylphenyl)-4-hydroxypiperidine hydrochloride (from example 3 step E). iH NMR CD3OD δ 8.94 (IH, d, 1.4Hz), 7.72 (2H, d, J=8.0Hz), 7.48 (IH, s), 7.43 (2H, d, J=8.0Hz), 7.20-6.97 (4H, m), 5.46 (2H, s), 4.28 (IH, d, J=l 1Hz), 3.85 (2H, s), 3.76 (IH, d, J=l 1.0Hz), 3.67 (3H, s), 3.02 (IH, m), 2.93 (2H, s), 2,57 (IH, dt, J=3.0 and 19.0Hz), 2.29 (3H, s), 2.20 (2H, d, J=20.0 Hz), and 1.60-1.38 (2H, m)ppm. Anal. Calcd for C28H30N4θ3 « 1.70TFA, 0.35H2O: C, 56.23 H, 4.87; N, 8.35. Found: C, 56.21 ; H, 4.86; N, 8.75. EXAMPLE 6 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl}-4-(4- methylbenzyl))isonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzyl bromide with 4-methylbenzyl bromide FAB MS 471(MH+). Anal. Calcd for C28H3lN4θ3*1.95HCT. 0.05H2O: C, 61.98 H, 5.95; N, 10.33. Found: C, 62.00; H, 5.89; N, 10.38. EXAMPLE 7 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl }-4-(3- methylbenzyl))isonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzyl bromide with 3 -methy lbenzy 1 bromide FAB MS 471(MH+). Anal. Calcd for C28H31N4O3 .8OHCI: 0.05H2O: C, 62.62H, 5.99; N, 10.43. Found: C, 62.59; H, 5.96; N, 10.36. EXAMPLE 8 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl}-4- (2.4-dichlorobenzyl )isonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzyl bromide with 2,4-dichlorolbenzyl bromide FAB MS 525(MH+). Anal. Calcd for C27H26N4O3CI2 .OHCM .6OH2O: C, 54.90H, 5.15; N, 9.48. Found: C, 54.85; H, 4.76; N, 9.47. EXAMPLE 9 Preparation of N-{ [l-(4-Cyanobenzyl)-l H-imidazol-5-yl]acetyl }-4-(3- methoxybenzyDisonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzyl bromide with 3-methoxybenzyl bromide FAB MS 487(MH+). Anal. Calcd for C27H26N4θ3Cl2- 80HCl: C, 60.90; H, 5.80; N, 10.15. Found: C, 60.90; H, 5.77; N, 10.13. EXAMPLE 10 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl }-4-(l - naphthylmethyPisonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methyIbenzyl bromide with 1-naphthylmethyl bromide. FAB HRMS exact mass calcd for C27H28N4O3CI: 507.239616(MH+); found 507.239124. Anal. Calcd for C3 lH3θN4θ3 « 2.25TFA: 0.40H2O: C, 55.35 H, 4.32; N, 7.27. Found: C, 55.36H, 4.30; N, 7.36. EXAMPLE 1 1 Preparation of N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl Jacetyl } -4-(4- chlorobenzyPisonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzyl bromide with 4-chlorobenzyl bromide. FAB HRMS exact mass calcd for C27H28N4O3CI: 491.184994(MH+); found 491.184736. Anal. Calcd for C27H27N4θ3Cl » 2.30 TFA: 0.15H2O: C, 50.21 H, 3.95; N, 7.41. Found: C, 50.18 H, 3.95; N, 7.46. EXAMPLE 12 Preparation of N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yllacety 1 } -4- (2.3-dichlorobenzyl)isonipecotic acid methyl ester. The title compound was prepared using the procedure above substituting 2-methylbenzylbromide with 2,3- dichlorobenzyl bromide. FAB HRMS exact mass calcd for C27H27N4O3CI2: 525.146021 (MH+); found 525.144945. Anal. Calcd for C27H26N4θ3Cl2*1.85 TFA: 0.45H2O: C, 49.53 H, 3.89; N, 7.53. Found: C, 49.51 H, 3.90; N, 7.73. EXAMPLE 13 Preparation of N-{ l-(4 Cyanobenzyl)- lH-imidazol-5-yl- aminocarbonyl }-4-(2-methylbenzyl) isonipecotic acid methyl ester. Step A: 1 -(4 Cvanobenzyl)-5-nitro- 1 H-imidazole. A solution of 4-nitroimidazole (2,25g, 19.9mmol) and 4- cyanobenzyl bromide (3.90g, 19.9mmol) in acetonitrile (10 ml) was stirred at 50°C for 72 hrs. The reaction was allowed to cool to room temperature and diethyl ether (70ml) was added. The precipitate was removed by filtration and the filtrate partitioned between EtOAc and NaHCθ3 solution. The organic extract was dried (MgS04) and the solvent evaporated in vacuo. The residue was chromatographed (Siθ2, 5% MeOH in CH2CI2) to afford a solid that was triturated with hot ethanol, and washed with diethyl ether, to afford the product as an off white solid. Step B: l-(4 CyanobenzyP-5- amino- lH-imidazole hydrochloride. A solution of l-(4 cyanobenzyl)-5- nitro-lH-imidazole (lOOmg, 0.438mmol) and 10% palladium on carbon was hydrogenated in the presence of 1 equivalent of HCl under Parr conditions for lhr. Removal of the catalyst by filtration and evaporation of solvent in vacuo afforded the title compound. 'HNMR CD3OD, δ 8,47(1H, d, J=1.7Hz), 7.71(2H, d, J=8.4Hz), 7.50(2H, d, J=8.4Hz), 6,55(1H, d, J=1.7Hz) and 5.36(2H, s)ppm. Step C: N- { 1 -(4 Cyanobenzyl)- 1 H-imidazol-5-yl-aminocarbony 1 } - 4-(2-methylbenzyl) isonipecotic acid methyl ester. To a suspension of 4-(2-methylbenzyl)-isonipecotic acid methyl ester hydrochloride (50mg, 0.176mmol) in toluene (2 ml) was added phosgene (0.912ml of a 1.93M solution in toluene, 1.76mmol) and triethylamine (0.074ml, 0.528mmol) and the mixture stirred for 48 hrs at room temperature. The excess phosgene was removed by purging the solution with argon gas for lOmin. The suspension was added to 1 - (4-cyanobenzyl)-5- amino- lH-imidazole hydrochloride (lOOmg, 0.528mmol) in CH2CI2 (10 ml) and the mixture stirrred at 50°C for 72 hrs. The solvent was evaporated in vacuo and the residue purified by preparative HPLC (C18, 95:5 to 5:95 water: acetonitrile containing 0.1% TFA). The residue after lyophilisation was partitioned between CH2CI2 and saturated NaHCθ3 solution. The organic extract was dried (MgSθ4), and evaporated to dryness FAB MS 472 (MH+). I HNMR CDC13 δ 7.60(2H, d, J=8.1 Hz), 7.28-6.90(8H, m), 5.30(2H, s), 3.90(2H, d, J=13.1Hz), 3.65(3H, s), 2.86(2H, s), 2.80(2H,d, J=11.9Hz), 2.30-2.10( 5H, m) and 1.80- 1.40(2H, m) ppm. EX AMPLE 14 2(R,S)-N { -2- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]2-(4- cyanobenzvPl acetyl-4-(2-methylbenzyl)-isonipecotic acid methyl ester. Step A: 2-{ l-(Triphenylmethyl)-lH-imidazol-4-yl}-2-(4- cyanobenzyP-acetic acid methyl ester. A solution of 1 -(triphenylmethyl)- lH-imidazol-4-ylacetic acid methyl ester (977mg, 2.55mmol) in THF (25 ml) was cooled to -78°C. Lithium hexamethyldisilazide (2.68ml, 2.68mmol) was added dropwise and the reaction stirred 30min at -78°C. 4-Cyanobenzyl bromide (500.7mg, 2.68mmol) was added and the reaction stirred a furthur 4 hrs at -78°C and then at -20°C for 12hr. The reaction was quenched with water (10ml) and saturated NaHC03 solutuon (10ml) and extracted with EtOAc. The organic extracts were dried (MgS04) and the solvent evaporated in vacuo.. Chromatography of the residue (Siθ2, 3% MeOH in CH2CI2) afforded the product. I HNMR CDCI3, δ 7.55-6.90(20H, m), 6.55(1H, m), 3.90(1H, t, J=7.7Hz), 3.66(3H, s) and 3.31(2H, m) ppm. Step B: 2-{ 1 -(Triphenylmethyl)- lH-imidazol-4-yl }-2-(4- cyanobenzyP-acetic acid. A solution of the 2- { 1 -(triphenylmethyl)- lH-imidazol-4- yl}-2-(4-cyanobenzyl)-acetic acid methyl ester in THF was treated with 1 equivalent of IM lithium hydroxide solution. Upon consumption of starting material as determined by t.l.c, 1 equivalent of hydrochloric acid was added and the solution evaporated to dryness in vacuo. The material obtained in this manner could be used without furthur purification. Step C: 2(R,S)- { 1 -(Triphenylmethyl)- 1 H-imidazol-4-yl } -2-(4- cyanobenzyl)-acetyl-4-(2-methylbenzyl) isonipecotic acid methyl ester. To a mixture of 4-(2-methylbenzyl)-isonipecotic acid methyl ester hydrochloride (72mg, 0.25mmol), and 2-{ 1- (triphenylmethyl)-lH-imidazol-4-yl}-2-(4-cyanobenzyl)-acetic acid(123mg, 0.25mmol), HOOBT (42mg, 0.25mmol) and triethylamine (0.088ml, 0.636 mmol) in DMF (3ml), was added EDC (54mg, 0.25mmol) and the reaction stirred at room temperature for 18hrs. The reaction was diluted with EtOAc and washed with saturated NaHCθ3 solution, the organic extracts were dried (Na2S04), and the solvent evaporated in vacuo.. The residue was purified by chromatography(Siθ2, gradient elution, l-5%MeOH in CH2CI2) to afford the product. Step D: 2(R,S)-N { -2- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]-2-(4- cyanobenyl) } acetyl-4-(2-methylbenzyl)-isonipecotic acid methyl ester. To a solution of 2(R,S)-2-{ { 1 -(triphenylmethyl)- 1H- imidazol-4-yl } -2-(4-cyanobenzyl) } -acetyl-4-(2-methylbenzyl)- isonipecotic acid methyl ester (96mg, 0.338 mmol) in acetonitrile (2 ml), was added 4-cyanobenyl bromide (24.5mg, 0.338 mmol) and the mixture heated at 55°C for 5hrs. The solvent was evaporated and the residue purified by preparative HPLC (C18, gradient elution, 95:5 to 5:95 water: acetonitrile containing 0.1 % TFA) to afford the title compound after lyophilisation. FAB HRMS exact mass calcd for C36H36N5O3 586.281815(MH+); found 586.280827. EXAMPLE 15 Preparation of N-{ [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yllacetyl }-4- (2-methylbenzyl)isonipecotic acid methyl ester. Step A: 2- [l-(Naphth-2-ylmethyl)-lH-imidazol-5-yI)]acetic acid methyl ester. To a solution of the product of example 4 step B (4.36g, 11.4 mmol) in acetonitrile (70 ml) was added 2-(bromomethyl)- naphthalene and heated to 55°C for 4hr. The reaction was cooled to room temperature and the resulting white precipitate was collected by filtration. The filtrate was concentrated to 30 ml and heated at 55°C for 18 hr. After this time, the reaction was cooled to room temperature and the resulting white precipitate collected by filtration. The filtrate was concentrated to 10 ml volume and heated to 55°C for 1 hr. The reaction was cooled to room temperature and diluted with ethyl acetate (25 ml). The resulting precipitate was collected by filtration and combined with the previous 2 precipitates in methanol (100 ml) and heated to reflux for 30 min. After this time, the solvent was removed in vacuo and the resulting residue was partitioned between methylene chloride (200 ml) and saturated sodium bicarbonate solution (100 ml). The organic layer was evaporated to dryness in vacuo and the residue purified by chromatography (Siθ2, gradient elution, 0-6% methanol in methylene chloride) to provide the title compound as an off white solid. IHNMR CDC13, δ 7.82(2H, m), 7.75(1H, m), 7.70(1H, s), 7.49(3H, m), 7.20(1H, d, J=8.4Hz), 7.06(1H, s), 5.32(2H, s), 3.57(3H, s) and 3.49(2H, s) ppm. Step B: 2-[l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl]acetic acid hydrochloride. 2-[ l-(Naphth-2-ylmethyl)-lH-imidazol-5-yl]acetic acid methyl ester (0.92g, 3.28mmol ) was dissolved in 2.5N hydrochloric acid ( 50ml ) and heated to 55°C for 3hr. After this time, the solution was concentrated to dryness in vacuo to give the title compound as a white solid. IHNMR CD3OD, δ 8.92(1H, s), 7.94(1H, d, J=8.6Hz), 7.88(2H, m), 7.83(1H, s), 7.54(3H, m), 7.43(1H, d, J=14.0Hz), 5.60(2H, s) and 3.82(2H, s) ppm. Step C: N- { [ 1 -(Naρhth-2-ylmethyl)- lH-imidazol-5-yl]acetyl } -4-(2- methylbenzyPisonipecotic acid methyl ester. The title compound was prepared using the procedure from example 4 step E, substituting 4-(2-methylbenzyl)-isonipecotic acid methyl ester hydrochloride for 4-(3-methylphenyl)-4- hydroxypiperidine hydrochloride and the acid from step B. FAB HRMS exact mass calcd for C31H34N3O3 496.260017(MH+); found 496.260274. Anal. Calcd for C3lH33N3θ3 « 2.65HCl: C, 62.87 H, 6.07; N, 7.10. Found: C, 62.85; H, 5.88; N, 7.14. iH NMR CD3OD δ 8.96 (IH, s), 8.00-7.80(3H, m), 7.76(1H, s), 7.56(2H, m), 7.46(1H, m), 7.35(1H, d, J=6.8Hz), 7.20-7.00(3H, m), 6.92(1H, d, J=7.0Hz), 5.56(2H, s), 4.18(1H, m), 3.80(2H, s), 3.62(3H, s), 3.62(1H, m), 3.0-2.70(3H, m), 2.35(1H, t, J=8.0Hz), 2.23(3H, s), 2.06(2H, d, J=13.3Hz) and 1.40-1.20(2H, m)ppm. EXAMPLE 16 Preparation of N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl Jmethy 1 } -4- methoxymethyl-4-(2-methylbenzyl) piperidine. Step A: N-t-butoxycarbonyl isonipecotic acid benzyl ester. To a solution of N-t-butoxycarbonyl isonipecotic acid (12.0 g, 52.3 mmol) from example 3 step A, in anhydrous CH2CI2 (100ml), was added benzyl alcohol (6.0 ml, 58 mmol), followed by EDC ( 11.04 g, 57.6 mmol), and DMAP (642 mg, 5.25 mmol). The resulting mixture was stirred for 6 hrs, then diluted with CH2CI2 (150 ml) and washed successively with water, 10% aqueous citric acid, saturated NaHCθ3, and brine and dried (MgSθ4). Concentration in vacuo afforded a colorless oil which was chromatographed (Siθ2, 20% EtOAc in hexanes) to afford the product as a white solid. Step B: N-t-Butoxycarbonyl-4-(2-methylbenzyl) isonipecotic acid benzyl ester. To a solution of N-t-butoxycarbonyl isonipecotic acid benzyl ester (13.34 g, 41.8 mmol) in THF (100ml) at -78°C was added sodium bis-trimethysilylamide (59 ml of a 1.0 M THF solution, 59 mmol) over 15 min. The resulting orange solution was stirred at -78°C for 1 hr and then treated dropwise with 2-methyl benzyl bromide (6.80 ml, 50.7 mmol) and then allowed to warm slowly to room temperature over 16 hrs. The reaction was quenched with saturated aqueous NH4CI, diluted with H2O, and extracted with EtOAc. The combined organic extracts were washed with brine, and concentrated in vacuo to an orange gum. Chromatography (Siθ2, gradient elution, 20 to 30% EtOAc in hexanes) afforded the product as a white solid. Step C: N-t-Butoxycarbonyl-4-hydroxymethyl-4-(2-methylbenzyl) piperidine. To a suspension of lithium aluminum hydride (0.32 g, 8.4 mmol) in anhydrous ether (50 ml) was added a solution of 4- (2- methylbenzyl)-N-t-butoxycarbonyl isonipecotic acid benzyl ester (3.0 g, 7.1 mmol) in anhydrous ether (25 ml) over 15 min. The resulting mixture was heated at gentle reflux for 1 hr. The reaction mixture was then quenched with the slow and successive addition of H2O (0.32 ml), 15% aqueous NaOH (0.96 ml), and H2O (0.96 ml). After stirring for 30 min, the mixture was filtered through celite and the filtrate washed with brine, dried (MgS04), and concentrated in vacuo to a colorless syrup. Purification by chromatography (Siθ2, gradient elution, 25 to 50% EtOAc in hexanes), afforded the product as a colorless gum. This material was recrystallized from EtOAc and hexane to afford a white solid, m.p. 104-106°C. Step D: N-t-Butoxycarbonyl-4-methoxymethyl-4-(2- methylbenzyPpiperidine To a suspension of sodium hydride (19 mg, 0.80 mmol) in 1.5 ml of THF, at 0°C was added a solution of N-t-butoxycarbonyl- 4-hydroxymethyl-4-(2-methylbenzyl)piperidine (200 mg, 0.63 mmol) in THF (1 ml ). The mixture was allowed to warm to room temperature. To this suspension was added anhydrous DMSO (0.35 ml) and the mixture was heated to 60°C and stirred 5 hrs until the solution was almost homogeneous. The reaction mixture was allowed to cool to room temperature and methyl iodide (0.070 ml, 1.12 mmol) was added. The resulting heterogeneous mixture was stirred at room temperature for 16 hrs. The reaction mixture was treated with 10% aqueous citric acid and extracted with diethylether. The combined etheral extracts were washed successively with saturated aqueous NaHCθ3 brine, dried (MgSθ4), and concentrated in vacuo to a yellow gum. Chromatography (Siθ2 > 9% EtOAc in hexanes) afforded the product as a colorless gum. Step E: 4-Methoxymethyl-4-(2-methylbenzyl)-piperidine hydrochloride salt. N-t-Butoxycarbonyl-4-methoxymethyl-4-(2-methylbenzyl) piperidine was deprotected as in Example 1 , Step G to afford the product as a white solid. Step F: N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y ljmethyl } -4- methoxymethyl-4-(2-methylbenzyl) piperidine. The title compound was prepared using the procedure from example 1 step H using 4-methoxymethyl-4-(2-methylbenzyl) piperidine hydrochloride. FAB HRMS exact mass calcd for C27H33N4O 429.265437 (MH+); found 429.265817. iH NMR CD3OD δ 8.77 (IH, s), 7.79(2H, d, J=8.4Hz), 7.78(1H, s), 7.41(2H, d, J=8.4Hz), 7.20-7.05(4H, m), 5.61 (2H, s), 4.36(2H, s), 3.36(3H, s), 3.35-3.10(6H, m), 2.78(2H, m), 2.31 (3H, s) and 1.90- 1.60(4H, m)ppm. EXAMPLE 17 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]acetyl }--4- methoxymethyl-4-(2-methylbenzyl) piperidine. The title compound was prepared using the procedure from example 4 step E using 4-methoxymethyl-4-(2-methylbenzyl) piperidine hydrochloride. FAB HRMS exact mass calcd for C28H33N4O2 457.260352 (MH+); found 457.260528. iH NMR CD3OD δ 8.94 (IH, s), 7.69(2H, d, J=8.4Hz), 7.47(1H, s), 7.41(2H, d, J=8.4Hz), 7.20-7.05(4H, m), 5.46(2H, s), 3.87(1H, m), 3.80(2H, m), 3.60(1H, m), 3.36(3H, s), 3.26(2H, m), 3.15(1H, m), 2.77(2H, s), 2.33(3H, s) and 1.70-1.35(4H, m)ppm. EXAMPLE 18 Preparation of N- { [ 1 -(4-Cyanobenzy 1)- 1 H-imidazol-5-y l]acetyl } -4- hydroxymethyl-4-(2-methylbenzyP piperidine. The title compound was prepared using the procedure from example 4 step E using 4-hydroxymethyl-4-(2-methylbenzyl) piperidine hydrochloride ( which was obtained from treatment of N-t- butoxycarbonyl-4-hydroxymethyl-4-(2-methylbenzyl) piperidine with gaseous HCl in EtOAc and evaporation of solvent. Anal. Calcd for C27H30N4θ2*1.75TFA-0.15H2θ: C, 56.81 ; H, 5.01 ; N, 8.69. Found: C, 56.81 ; H, 5.02; N, 8.83. EXAMPLE 19 Preparation of N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y l]ethy 1 } -4-(2- methylbenzyPisonipecotic acid methyl ester. Step A: 5-[l -(4-cyanobenzyl)-lH-imidazolyl]ethanol. To a stirred solution of the ester from example 4 step C, (1.50g, 5.88mmol), in methanol (20 ml) at 0°C, was added sodium borohydride (l.OOg, 26.3mmol) portionwise over 5 min. The reaction was stirred at 0°C for 1 hr and then at room temperature for an additional 1 hr. The reaction was quenched by the addition of saturated NH4CI solution and the methanol evaporated in vacuo.. The residue was partitioned between EtOAc and saturated NaHCθ3 solution and the organic extracts dried, (MgSθ4) and evaporated in vacuo. The residue was purified by chromatography (Siθ2, gradient elution, 4 to 10% methanol in methylene chloride) to afford the title compound as a white solid. iH NMR CDCI3 δ 7.64(2H, d, J=8.2Hz), 7.57(1H, s), 7.11 (2H, d, J=8.2Hz), 6.97(1H, s), 5.23(2H, s), 3.79(2H, t, J=6.2Hz), 2.66(2H, t, J=6.2Hz) ppm. Step B: 5-(-l-(4-CyanobenzyP-imidazolyI)ethylmethanesulfonate. A solution of 5-[l-(4-cyanobenzyl)-lH-imidazolyl]ethanol (0.500 g, 2.20 mmol) in methylene chloride (6 ml) at 0°C was treated with Hunig's base (0.460ml, 2.64mmol) and methanesulfonyl chloride (0.204ml, 2.64mmol). After 2 hrs, the reaction was quenched by addition of saturated NaHCθ3 solution (50ml) and the mixture extracted with methylene chloride (50ml), dried (MgSθ4) and the solvent evaporated in vacuo. The title compound was used without furthur purification. iH NMR CDCI3 δ 7.69 (IH, s) 7.66(2H, d, J=8.2Hz), 7.15 (2H, d, J=8.2Hz), 7.04(1 H, s), 5.24(2H, s), 4.31(2H, t, J=6.7Hz), 2.96(3H, s), and 2.88(2H, t, J=6.6Hz)ppm. Step C: N-{[l-(4-Cyanobenzyl)-lH-imidazol-5-yl]ethyl }-4-(2- methylbenzyPisonipecotic acid methyl ester. A solution of 5-(-l-(4-cyanobenzyl)-imidazolyl) ethyl methanesulfonate (223 mg, 0.73 mmol) in DMF (6.0 ml) was added to 4-(2-methylbenzyl isonipecotic acid methyl ester hydochloride (207.2mg, 0.73mmol), sodium iodide (438mg, 2.92 mmol) and K2CO3 (252mg, 1.82mmol). The mixture was stirred at 55°C for 3 hrs and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (C18, gradient elution, 95:5 to 5:95% water: acetonitrile, containing 0.1 % TFA). Lyophilisation afforded the TFA salt which was converted to the HCl salt, by partioning between CH2CI2 and a saturated NaHCθ3 solution. The organic extract was dried (MgS04 ) and treated with aqueous HCl in acetonitrile and lyophilised. Anal. Calcd for C28H32N4θ2*2.55HCl-2.55H2θ: C, 56.14; H, 6.74; N, 9.35. Found: C, 56.12; H, 6.74; N, 9.02. FAB HRMS exact mass calcd for C28H33N4O2 457.260352 (MH+); found 457.260675. iH NMR CD3OD δ 9.05 (IH, s), 7.80(2H, d, J=8.2Hz), 7.61 (1H, s), 7.53(2H, d, J=8.2Hz), 7.20-7.00(4H, m), 5.66(2H, s), 3.71(3H, s), 3.58(2H, d, J-.12.3), 3.38(2H, m), 3.18(2H, m), 2.90(2H, s), 2.90(2H, t, J=13Hz), 2.40(2H, d, J=12.2Hz), 2.37(3H, s),and 2.10(2H, t, J=12.2Hz) ppm. EXAMPLE 20 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl} - trans - 4-(3-methylphenyl)-3-hydroxypiperidine. Step A: N-t-Butoxycarbonyl-4-(3-methylphenyl)-piperid-3-ene. To a solution of N-t-butoxycarbonyl-4-(3-methylphenyl)-4- hydroxy piperidine (from example 1 step F), (1.57g, 5.40mmol) in pyridine (25 ml) at 0°C was added phosphorous oxychloride (1.01 ml, 10.7mmol) and the reaction stirred 16 hrs at room temperature. The reaction was diluted with water and partitioned between EtOAc and 10% aqueous citric acid solution. The organic extracts were washed with NaHCθ3 and brine, dried (MgSθ4), and the solvent evaporated in vacuo. Chromatography of the residue (Siθ2, 10:90 EtOAc in hexanes) afforded the product as an oil. iH NMR CDCI3 δ 7.40-7.00(4H, m), 6.03(1H, s), 4.08(2H, s),3.64(2H,t, J=5.5Hz), 2.52(2H, s), 2.37(3H, s) and 1.51(9H, s)ppm. Step B: s-N-t-Butoxycarbonyl-4- (3-methylphenyl)-3 hydroxy piperidine To a solution of N-t-butoxycarbonyl-4- (3-methylphenyl)- piperid-3-ene, (0.705g, 2.58mmol) in THF (3 ml) at 0°C was added borane (3.09ml of a IM solution in THF, 3.09 mmol) and the reaction stirred 4 hrs at room temperature. The reaction was cooled to 0°C and treated carefully with NaOH (3 ml of a 2.5M solution, and then 30% hydrogen peroxide (10ml) and the reaction stirred for 2 hrs at room temperature. The reaction was diluted with water andextracted with EtOAc . The organic extracts were washed with NaS2θ3, brine, dried (MgSθ4), and the solvent evaporated in vacuo.. Chromatography of the residue (Siθ2, 25:75 EtOAc in hexanes) afforded the product as an oil. iH NMR CDC13 δ 7.40-7.20(lH, m), 7.20-7.0(3H, m), 4.40(1H, brs), 4.18(1H, brs), 2.75(1H, m), 2.62(1H, m), 2.44(1H, m), 2.35(3H, s), 1.90-1.60(3H, m), 1.49(9H, s) ppm. Step C: trans-4- (3-Methylphenyl)-3 hydroxypiperidine hydrochloride. To a solution of trans -N-t-butoxycarbonyl-4- (3- methylphenyl)-3 hydroxypiperidine, (0.20g, 0.12 mmol) in EtOAc (50 ml) at 0°C was bubbled HCl gas until saturated. The reaction was stirred at 0°C for 10 min and then the solvent evaporated in vacuo to afford the product as a white foam. iH NMR δ CDCI3 7.22(1H, t, J=7.3Hz), 7.20-7.0(3H, m), 3.95(1 H, m), 3.54-3.36(2H, m), 3.07(1H, dt, J=3.3 and 14.6Hz), 2.84(1H, t, J=10.8Hz), 2.70(1H, m), 2.34(3H, s), 2.10- 1.80(2H, m) ppm. Step D: N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl } -trans-4- (3-methylphenyl)-3 hydroxy piperidine. The title compound was prepared by the procedure in example 1 step H using trans- 4- (3-methylphenyl)-3 hydroxy piperidine hydrochloride. Anal. Calcd for C24H26N4O-2.55TFA-0.05H2O: C, 51.54; H, 4.26; N, 8.26. Found: C, 51.53; H, 4.24; N, 8.42. FAB HRMS exact mass calcd for C24H27N4O 387.218487 (MH+); found 387.216845. EX AMPLE 21 Preparation of N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl} -trans- 4- (3-methylphenyP-3 methoxy piperidine. Step A: fraπs-N-t-Butoxycarbonyl-4- (3-methylphenyl)-3- methoxy piperidine To a solution of Jrø/z.s-N-t-butoxycarbonyl-4- (3- methylphenyl)-3 hydroxy piperidine (117mg, 0.402mmol), in DMF (2 ml) at 0°C was added sodium hydride (24 mg of a 60% dispersion in mineral oil, 0.803mmol). After 10 min, methyl iodide (0.050ml, 0.803mmol) was added and the reaction allowed to warm to room temperature over 16 hrs. The reaction was quenched by the addition of saturated NH4CI solution (5 ml) and extraction with EtOAc. The organic extracts were washed with brine and dried, (MgSθ4) and the solvent evaporated in vacuo . Chromatography of the residue (Siθ2, 10- 15% EtOAc in hexanes) afforded the title compound as an oil. iH NMR CDC13 δ 7.20(1H, t, J=7.5Hz), 7.20-7.0(3H, m), 4.50(1H, brs), 4.12(1H, brs), 3.28(1H, m), 3.17(3H, s), 2.75(1H, t, J=12.3Hz), 2.60-2.45(2H, m), 2.34(3H, s), 1.85-1.60(2H, m), 1.495(9H, s) ppm. Step B: trans-4- (3-Methylphenyl)-3 methoxy piperidine hydrochloride. To a solution of frøw.s-N-t-butoxycarbonyl-4- (3- methylphenyl)-3 methoxy piperidine, (0.20g, 0.65mmol) in EtOAc (50 ml) at 0°C was bubbled HCl gas until saturated. The reaction was stirred at 0°C for 10 min and then the solvent evaporated in vacuo to afford the product as a white foam. iH NMR δ CDCI3 7.22(1H, t, J=7.3Hz), 7.20-7.0(3H, m), 3.80-3.60(2H, m), 3.35(1H, m), 3.15(3H, s), 3.07(1H, m), 2.90-2.70(2H, m), 2.36(3H, s) and 2.10-1.95(2H, m) ppm. Step C: N- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-y ljmethyl } -trans-4- (3-methylphenyl)-3-methoxy piperidine. The title compound was prepared by the procedure in example 1 step H using trans-4- (3-methylphenyl)-3 methoxy piperidine hydrochloride. Anal. Calcd for C24H26N4O-2.65TFA-0.45H2O: C, 51.20; H, 4.47; N, 7.88. Found: C, 51.18; H, 4.45; N, 7.90. FAB HRMS exact mass calcd for C25H29N4O 401.234137 (MH+); found 401.233036. EXAMPLE 22 Preparation of N-{ [l-(4-cyanobenzyl)- 1 H-imidazol-5-yl]methyI } -trans- 4- (3-methylphenyP-3 benzyloxy piperidine. Step A: £πms-N-t-Butoxycarbonyl-4- (3-methylphenyl)-3 benzyloxy piperidine. To a solution of trans-N-t-butoxycarbonyl-4- (3- methylphenyl)-3 hydroxy piperidine (131mg, 0.449mmol), in DMF (2 ml) at 0°C was added sodium hydride (27mg of a 60% dispersion in mineral oil, 0.890mmol). After 10 min, benzyl bromide (0.107ml, 0.890 mmol) was added and the reaction allowed to warm to room temperature over 16 hrs. The reaction was quenched by the addition of saturated NH4CI solution (5 ml) and extraction with EtOAc. The organic extracts were washed with brine and dried (MgSθ4) and the solvent evaporated in vacuo. Chromatography of the residue (Siθ2, gradient elution, 10-15% EtOAc in hexanes) afforded the title compound as an oil. iH NMR CDCI3 δ 7.30-6.90(9H, m), 4.40(2H, brs), 4.25-4.05(2H, brs), 3.40(1H, m), 2.80-2.55(3H, m), 2.32(3H, s), 1.85-1.60(2H, m), 1.48(9H, s) ppm. Step B: trans-4- (3-Methylphenyl)-3-benzloxypiperidine hydrochloride. To a solution ofrrø«.s-N-t butoxycarbonyl-4-(3- methylphenyl)-3-benzyloxy piperidine, (0.137g, 3.60mmol) in EtOAc (50 ml) at 0°C was bubbled HCl gas until saturated. The reaction was strirred at 0°C for 10 min and then the solvent evaporated in vacuo to afford the product as a white foam. iH NMR CD3OD δ 7.30-6.90(9H, m), 4.37(1H, d, J=11.5Hz), 4.17(1H, d, J=11.5Hz), 3.87(1H, dt, J=4.5 and 10.4Hz), 3.66(1H, dd, J=4.4 and 13.3Hz), 3.42(1H, d, J=12.3Hz), 3.07(1H, dt, 4.0 and 12.3 Hz), 2.93- 2.76(2H, m), 2.31 (3H, s) and 2.20- 1.93(2H, m) ppm. Step C: N-{ [l -(4-Cyanobenzyl)-lH-imidazol-5-yl]methyl } -trans-4- (3-methylphenyl)-3-benzyloxy piperidine. The title compound was prepared by the procedure in example 1 step H using frø«.ϊ-4-(3-rnethylphenyl)-3- benzyloxypiperidine hydrochloride. FAB HRMS exact mass calcd for C31H33N4O 477.265437 (MH+); found 477.265776. EXAMPLE 23 Preparation of l-[2(R,S)-Amino-3-(2-tetradecyloxyphenyl)propyll-4-(2- methylbenzyPisonipecotic acid methyl ester dihydrochloride salt Step A: 3-(2-hydroxyphenyl)-2-(N-t-butoxycarbonyl- amino)propanol To a solution of D,L-N-t-Butoxycarbonyl-ortho-tyrosine methyl ester (1.34 g, 4.54 mmol) in THF (20 mL) at 0°C was added lithium aluminum hydride (400 mg, 10.5 mmol) portionwise. After 4 hrs at room temperature, H2O (0.4 ml) was added dropwise followed by I N NaOH (0.4 ml) and then H2O (1.2 ml) . The slurry was stirred for 1 hour, filtered through celite, rinsed with THF and the solvent was evaporated in vacuo.. Chromatography of the residue (Siθ2, 50% EtOAc in hexanes) gave the title compound as a solid. Step B: 3-(2-Tetradecyloxyphenyl)-2(R,S)-(N-t-butoxycarbonyl- amino)propanol. A mixture of the alcohol from Step A (218 mg, 0.82 mmol), tetradecyl bromide (170 μL, 0.9 mmol) and CsC03 (532 mg, 1.63 mmol) in DMF (8 mL) was stirred for 16 hs at room temperature under argon. The mixture was poured into water and extracted with EtOAc. The organic extracts were combined, washed with water and brine, dried (MgSθ4), and concentrated in vacuo to give an oil. Purification by chromatography (Siθ2, 20% EtOAc in hexanes) gave the title compound as a solid. Step C: 3-(2-Tetradecyloxyphenyl)-2(R,S)-(N-t butoxycarbonylamino)propanal To a solution of the alcohol from Step B (135 mg, 0.29 mmol) in CH2CI2, (1.0 ml), DMSO, (1.0 ml) and E-3N (0.2ml) at room temperature under argon was added pyridine-S03 complex (185 mg, 1.17 mmol). The mixture was stirred for 3 hrs and then poured into brine, and extracted with EtOAc. The organic extracts were combined, washed with brine, dried (MgSθ4) and concentrated in vacuo to give the title compound as an oil. iH NMR CDCI3 δ 9.59 (s, IH), 7.25-7.10 (m, 2H), 6.95-6.80 (m, 2H), 5.42 (d, IH), 4.35 (m, IH), 3.96 (brt, 2H), 3.13 (m, 2H), 1.82 (m, 2H), 1.50-1.20 (m, 31 H), 0.89 (brt, 3H). Step D: l-[2(R,S)-N-t-Butoxycarbonylamino-3-(2- tetradecyloxyphenyl)propyl]~4-(2-methylbenzyl) isonipecotic acid methyl ester. The aldehyde (138 mg, 0.30 mmol) obtained in Step C was dissolved in dichloroethane (2.5 ml) and treated with the piperidine hydrochloride from example 3 step D (75 mg, 0.27 mmol) and Et3N (37.8 ml, 0.27 mmol). The solution was slurried with 4 A molecular sieves and stirred for 30 min at room temperature before adding sodium triacetoxyborohydride (172 mg, 0.81 mmol). After stirring for 18 hrs, the solution was filtered through celite. The filtrate was poured into EtOAc, washed with saturated NaHCθ3 solution, brine, dried (MgSθ4), and concentrated in vacuo to give an oil. Purification by chromatography (Siθ2, 30% EtOAc in hexanes) gave the title compound. iH NMR CDC13, δ 7.06 (m, 6H), 6.83 (m, 2H), 5.01 (brs, IH), 3.92 (m, 4H), 3.59 (s, 3H), 2.82 (m, 4H), 2.07 (m, 8H), 1.41 (m, 37H), 0.88 (brt, 3H). Step E: l-[2(R,S)-Amino-3-(2-tetradecyloxyphenyl)propyl]-4-(2- methylbenzyl)isonipecotic acid methyl ester dihydrochloride salt A solution of the N-t-butoxycarbonylamine from Step D (186 mg) in EtOAc (20 mL) was treated with HCl gas until saturated. After 15 min, the solvent was removed in vacuo to give the crude product as a solid which was triturated with Et2θ/hexane. The solvent was decanted and the residue dried in vacuo to give the title compound. Anal. Calcd. for C38H6ON2O3 • 2.4 HCl: C, 67.07; H,9.24; N, 4.12. Found: C, 67.10; H, 9.33; N, 4.29. FAB MS 593 (MH+). EXAMPLE 24 Preparation of N-2-(S)-aminolauroyl-4-( 1 -napthylmethyl) isonipecotic acid methyl ester. Step A: (S)-3-( 1 -Oxolauroyl)-4-(phenylmethyl-2-oxazolidinone. To a solution of (S)-4-Benzyloxazolidinone (8.85 g, 50 mmol) in 150 mL of anhydrous THF at -78 °C was added a 2.5 M solution of n-Butyllithium (25 mL, 52.5 mmol) over 10 min. After the addition, neat lauroyl chloride (12.7 mL, 55 mmol) was added and the resulting solution stirred at -78 °C for 0.5 hr. and then allowed to warm to room temperature over 0.5 hr. The mixture was quenched with saturated aqueous ammonium chloride and the solvent removed in vacuo. The residue was diluted with water and extracted with methylene chloride. The extracts were combined and washed with IM aqueous sodium hydroxide, brine, dried over sodium sufate and concentrated in vacuo to afford the product as a viscous yellow oil. iH NMR CDC13 δ 7.20-7.40 (m, 5 H), 4.70 ( m, 1 H), 4.20 (m, 2 H), 3.3 ( dd, J= 13.3, 3.3 Hz, 1 H), 2.90 (m, 2 H), 2.80 ( dd, J= 13.3, 9.7 Hz, 1 H) 1.70 ( m, 2 H), 1.3 0(m, 18 H), 0.90 (t, J= 6.7 Hz, 3 H) Step B: Preparation of (S)-3-(l-Oxo-(S)-2-azidolauroyl)-4- (phenylmethyl-2-oxazolidinone. To a solution of (S)-3-(l-Oxolauroyl)-4-(phenylmethyl-2- oxazolidinone.(3.6 g, 10 mmol) in anhydrous THF (60 ml), at -78 °C, was added ( 21 ml of a 0.5 M solution of potassium hexamethyldisilazide in toluene, 10.5 mmol). The resulting solution was stirred at -78 °C for 15 min. and then treated with a precooled solution of 2,4,6- triisopropylbenzenesulfonyl azide in anhydrous THF (25 ml). Two minutes after the addition, glacial acetic acid (2.3 ml, 40 mmol) was added and the reaction mixture was warmed to 25 °C in a water bath and stirred for 1.5 hrs. The reaction mixture was diluted with chloroform (300 ml) and washed successively with brine and dilute sodium bicarbonate solution. After drying over sodium sulfate the crude chloroform solution was concentrated in vacuo to a yellow oil which was chromatographed on (Si02, 5% EtOAc in hexanes). Evaporation in vacuo to afforded the product as a pale yellow viscous oil. iH NMR CDCI3 δ 7.2-7.4 (m, 5 H), 4.9 (dd, J=8.6, 5.0 Hz, 1 H), 4.7 ( m, 1 H), 4.2 (m, 2 H), 3.4 ( dd, J= 13.4, 3.2 Hz, 1 H), 2.8 ( dd, J= 13.4, 9.5 Hz, 1 H) 1.8 ( m, 2 H), 1.6- 1.2 (m, 18 H), 0.9 (t, J= 6.7 Hz, 3 H). Step C. (S)-3-(l-Oxo-(S)-2-N-t-butoxycarbonylaminolauroy (phenylmethyl-2-oxazolidinone. To an argon degassed solution of the above azide (2.88 g, 7.2 mmol) in ethyl acetate (150 mL) was added t-butoxycarbonyl anhydride (2.5 g, 11.5 mmol) and 10 % palladium on charcoal catayst (0.3g). This mixture was vigorously stirred under a balloon of hydrogen for 2 hrs. The catalyst was removed by filtration through celitChromatography (Siθ2, 15% EtOAc in hexanes) and evaporation of solvent vacuo, afforded the product as a white solid, m.p. 93.5- 94.5°C. i H NMR CDCI3 δ 7.2-7.4 (m, 5 H), 5.4 (m, 1 H), 5.2 ( br d, J= 9 Hz, 1 H), 4.6 (m, 1 H), 4.2 (m, 2 H), 3.3 ( m, 1 H), 2.8 ( m, 1 H) 1.8 (m, I H), 1.6-1.2 ( m, 26 H), 0.9 (t, J= 6.7 Hz, 3 H). Step D: Preparation of (S)-2-N-t-Butoxycarbonylaminolauric acid To an argon degassed solution of the above oxazolidinone in a 3: 1 THF: water mixture, under argon at 0°C , was added LiOH monohydrate (0.45g, 10.7 mmol). After stirring at 0 °C for 1.5 hrs, the mixture was diluted with 0.5 M aqueous sodium bicarbonate and extracted with methylene chloride. The aqueous portion was acidified with 3 M aqueous HCl and extracted with ethyl acetate. The combined extracts were dried (MgSθ4) and concentrated in vacuo to afford the product as a viscous oil. iH NMR (CDCI3) d 5.0 ( br d, J= 8 Hz, 1 H), 4.3 (m, 1 H), 1.8 (m, 1 H), 1.7 ( m, 1 H), 1.4 ( s, 9 H) 1.4-1.2 ( m, 16 H), 0.9 (t, J= 7 Hz, 3 H). Step E: N-2-(S)-t-Butoxycarbonylaminolauroyl-4-( 1 - napthylmethyl) isonipecotic acid methyl ester. The title compound was prepared according to the procedure in example 10 using the acid prepared in step D. Step F: N-2-(S)- Aminolauroyl-4-( 1 -napthylmethyl)-isonipecotic acid methyl ester . A solution of the product from Step E (100 mg) in EtOAc (10 ml) was treated with HCl gas until saturated. After 15 mins, the solvent was removed in vacuo to give the crude product which was purified by preparative HPLC (C18, gradient elution, 95:5 to 5:95 water: cetonitrile containing 0.1 % TFA) to afford the title compound as a white solid after lyophilisation. Anal. Calcd for C30-H44N2O3- 1.20TFA: C, 63.02 H, 7.38; N, 4.54. Found: C, 63.05; H, 7.42; N, 4.43. EXAMPLE 25 4-(Benzoxazolidin-2-one- 1 -yl)- 1 - [ 1 -(4-cyanobenzy l)-5- imidazolylacetyllpiperidine hydrochloride Step A: Preparation of lH-Imidazole-4- acetic acid methyl ester hydrochloride. A solution of lH-imidazole-4-acetic acid hydrochloride (4.00g, 24.6 mmol) in methanol (100 ml) was saturated with gaseous hydrogen chloride. The resulting solution was allowed to stand at room temperature (RT) for 18hr. The solvent was evaporated in vacuo to afford the title compound as a white solid. Step B: Preparation of 1 -(Triphenylmethyl)- lH-imidazol-4-ylacetic acid methyl ester To a solution of the product from Step A (24.85g, 0.141mol) in dimethyl formamide (DMF) (115ml) was added triethylamine (57.2 ml, 0.412mol) and triphenylmethyl bromide(55.3g, O. π imol) 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. iH NMR (CDC13, 400 MHz) d 7.35(1H, s), 7.31(9H, m), 7.22(6H, m), 6.76(1 H, s), 3.68(3H, s) and 3.60(2H, s) ppm. Step C: Preparation of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid methyl ester. To a solution of the product from Step B (8.00g, 20.9mmol) in acetonitrile (70 ml) was added bromo-p-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 (MgSθ4) and evaporated in vacuo to afford the title compound as a white solid : Step D: Preparation of [l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid. A solution of [l-(4-cyanobenzyl)-lH-imidazol-5-yljacetic acid methyl ester (4.44g, 17.4mmol ) in THF (100ml) and 1 M lithium hydoxide (17.4 ml, 17.4 mmol) was stirred at RT for 18 hr. 1 M HCl (17.4 ml) was added and the THF was removed by evaporation in vacuo. The aqueous solution was lyophilised to afford the titled compound containing lithium chloride as a white solid. Step E: Preparation of l-(t-?7 -butoxycarbonyl)-4- 2- hydroxyphenyPaminolpiperidine A 500 mL round bottom flask under inert atmosphere is charged with a magnetic stirring bar, 6.6 g (60 mmol) 2-aminophenol and 12 g (60 mmol) N-t-butyloxycarbonyl-4-piperidone. The solids are suspended in 50 mL each 1 ,2-dichloroethane and glacial HOAc, treated with 1 g powdered 4A molecular sieves, and stirred at room temperature 30 min. 12.8 g (60 mmol) NaBH(OAc)3 is added and the thick slurry stirred at room temperature 30 h. The reaction mixture is diluted with 200 mL CH2CI2 and quenched slowly with saturated NaHCθ3 solution, approx 100 mL. The layers are separated, the organic layer washed with 1 x 150 mL saturated NaHCθ3 solution, dried over MgSθ4, filtered and concentrated to provide a brown oil. Flash chromatography on silica (1 to 3% MeOH in CH2CI2 containing 0.5% cone. NH4OH) provided 16.8 g (57 mmol, 95%) of the desired aminoalcohol as a foam. Step F: Preparation of l-(ter/-butoxycarbonyl)-4-(benzoxaxolidin- 2-one- 1 -yPpiperidine A 1-L round bottom flask under inert atmosphere is charged with a magnetic stirring bar, 16.8 g (57 mmol) of the aminoalcohol from Step E and 500 mL freshly distilled THF, and the flask immersed in an ice- water bath. Stirring is initiated and when the solution becomes homogeneous, 12 mL (69 mmol) N,N- diisopropylethylamine is added followed by 5.7 g (19.2 mmol) triphosgene in one portion. The reaction is stirred at 0°C 30 min and then the ice- water bath removed and the reaction allowed to stir 15 h, wherein a precipitate is formed. The reaction mixture is filtered, concentrated to an oil and partitioned between 400 mL EtOAc and 200 mL saturated Na2Cθ3 solution. The layers are separated, the organic layer washed with 200 mL saturated Na2C03 solution, dried over MgS04, filtered and concentrated to an oil. Flash chromatography on silica (15 to 30 to 40% EtOAc in hexanes) provided 14.6 g (46 mmol, 80%) of the benzoxazolone as an amorphous solid. Step G: Preparation of 4-(benzoxaxolidin-2-one-l-yl)piperidine hydrochloride A 1-L round bottom flask is charged with a magnetic stirring bar, 14.6 g (46 mmol) benzoxazolone from Step F and 120 mL isopropanol. 60 mL 8 N HCl is added, the reaction becomes homogeneous and it is stirred 15 h wherein a precipitate forms. The reaction is concentrated by rotary evaporation and the solid dried azeotropically with 2 x 150 mL toluene and the resulting off white solid dried under vacuum to provide 11.5 g (45 mmol, 99%) of the amine hydrochloride salt. Step H: Preparation of 4-(benzoxaxolidin-2-one-l-yl)-l-[l-(4- cyanobenzyP-5-imidazolylacetynpiperidine hydrochloride To a solution of the acid from Step D (639 mg, 1.77 mmol), the amine hydrochloride salt from Step G (303 mg, 1.18 mmol), and HOOBT (295 mg, 1.81 mmol) in DMF (5 mL) was added EDC (347 mg, 1.81 mmol), followed by triethylamine (0.99 ml, 7.11 mmol) . The reaction was stirred at room temperature for 15 hrs, diluted with EtOAc, and the organic layer was washed with sat. aq NaHCθ3, brine, and dried (Na2Sθ4). and evaporated in vacuo. The resulting product was purified by silica gel chromatography (59% acetone/CH 2 θ 2 with 1% MeOH) to provide the desired amide which was taken up in CH 2 CI 2 and treated with excess 1 M HCl/ether solution, and concentrated in vacuo. The titled product hydrochloride (391 mg) was isolated as a white solid. FAB mass spectrum m/e 442 (M+l). Analysis calculated for C2 5 H 23 N 5 O 3 • 1.0 HCl • 0.55 H 2 0: C, 61.55; H, 5.19; N, 14.36; Found: C, 61.51 ; H, 5.23; N, 15.56. EXAMPLE 26 4-(l,2-Dihydro-4(H)-3,l-benzoxazin-2-one-l -yl)-l-[l-(4-cyanobenzyl)- 5-imidazolylacetyllpiperidine hydrochloride Step A: Preparation of 1 -ferr-butoxycarbonyM-l^- hydroxymethyPphenylaminolpiperidine N-r-butoxycarbonyl-4-piperidinone (20 g, 100 mmol), 2- aminobenzyl alcohol (13 g, 110 mmol), and acetic acid (14 mL, 220 mmol) were dissolved in dry toluene (500 mL). The solution was refluxed under inert atmosphere with azeotropic removal of water for 16 h. The solution was cooled to ambient temperature and to it was added NaBH3CN (14 g, 220 mmol) and dry THF (200 mL). The reaction was stirred at ambient temperature for 24 h. The reaction was concentrated under reduced pressure and the residue was dissolved in EtOAc (750 mL). The EtOAc layer was washed with saturated aqueous NaHCθ3 (4 x 500 mL) and brine (250 mL). The EtOAc layer was dried (MgSθ4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography, using a gradient elution of 15-30% EtOAc-hexanes. The titled compound was obtained as a gum. Step B: Preparation of l-[(l-t-butyloxycarbonyl)piperidin-4-yl]- 1 ,2-dihvdro-4(H)-3.1 -benzoxazin-2-one The product form Step A (24 g, 78 mmol) was dissolved in dry THF (250 mL) and cooled to 0°C. To the solution was added diisopropylethylamine (41 mL, 240 mmol) and triphosgene (8.54 g, 28.8 mmol). The reaction was stirred at 0 C for lh, and then at ambient temperature for 72 h. Ether (250 mL) was added, the mixture was cooled to 0°C for 3 h and then filtered to remove the hydrochloride salt of DIEA. The filtrate solvents were removed under reduced pressure and the residue was dissolved in EtOAc (750 mL). The EtOAc solution was washed with 5% aqueous citric acid (2 x 500 mL), water (250 mL), and saturated aqueous NaHC03 (2 x 500 mL). The EtOAc layer was dried (MgS04), filtered, and the solvent was removed under reduced pressure. The residue was boiled in ether (ca. 200 mL) until the solid had dissolved. Cooling overnight gave the titled product as off-white crystals. Step C: Preparation of l-(4-ρiperidinyl)-l ,2-dihydro-4(H)-3, l - benzoxazin-2-one hydrochloride A stirred solution of the product from Step B (19 g, 57 mmol) in EtOAc (500 mL) was cooled to 0 C. HCl gas was bubbled through the solution for 30 min. Stirring was continued at 0 C for 1 h, during which time a precipitate had formed, and then at ambient temperature for 1 h. The stirred suspension was cooled to 0 C and cold ether (250 mL) was added. After 1 h at 0°C, the solid was collected by filtration. The solid was dried under reduced pressure for 18 h, giving the titled compound as an off-white solid. Step D: Preparation of 4-(l,2-dihydro-4(H)-3,l-benzoxazin-2-one- l-yl)-l-[l-(4-cyanobenzyl)-5-imidazolylacetyl]piperidine hydrochloride To a solution of the acid from Step D of Example 25 (435 mg, 1.21 mmol), the amine hydrochloride salt from Step C (215 mg, 0.796 mmol), and HOBT (168 mg, 1.24 mmol) in DMF (6 mL) was added EDC (233 mg, 1.22 mmol), followed by triethylamine (0.66 ml, 4.8 mmol) . The reaction was stirred at room temperature for 15 hrs, diluted with EtOAc, and the organic layer was washed with sat. aq NaHCθ3, brine, and dried (Na2Sθ4). and evaporated in vacuo. The resulting product was taken up in CH2CI2 and treated with excess 1 M HCl/ether solution, and concentrated in vacuo. The titled product hydrochloride (335 mg) was isolated as a white solid. FAB mass spectrum m/e 456 (M+l). Analysis calculated for C26H25N 5 O 3 • 1.60 HCl • 0.85 H 2 0: C, 59.05; H, 5.39; N, 13.24; Found: C, 59.10; H, 5.40; N, 12.76. EXAMPLE 27 4-( 1 ,2-Dihydro-4(H)-3, 1 -benzoxazin-2-one- 1 -yl)- 1 -[ 1 -(4-cyanobenzyl)- 5-imidazolylmethyllpiperidine hydrochloride Step A: 4-( 1 ,2-dihydro-4(H)-3, 1 -benzoxazin-2-one- 1 -yl)- 1 -[ 1 -(4- cyanobenzyP-5-imidazolylmethyllpiperidine hydrochloride To a solution of the amine hydrochloride from Step C of Example 26 (135 mg, 0.502 mmol) in 10 mL of 1 ,2-dichloroethane at 0 °C was added 4A powdered molecular sieves (360 mg), followed by sodium triacetoxyborohydride ( 168 mg, 0.793 mmol). The imidazole carboxaldehyde from Step E of Example 1 (120 mg, 0.570 mmol) was added, and the reaction was stirred at 0 °C. After 56 hours, the reaction was poured into EtOAc, washed with dilute aq. NaHCθ3, and the aqueous layer was back-extracted with EtOAc. The combined organics were washed with brine, dried (Na2S04), filtered, and concentrated in vacuo. The resulting product was taken up in 10 mL of CH 2 CI 2 , and propylamine (2 mL) was added. The mixture was stirred for 12 hours, then concentrated in vacuo to afford a pale yellow foam. This material was purified by silica gel chromatography (50-80%% acetone/CH 2 θ 2 ), and the resultant white foam was taken up in CH 2 CP and treated with excess equivalents of 1 M HCl/ether solution. After concentrated in vacuo, the product dihydrochloride was isolated as a white powder. EXAMPLE 28 N- [2- { (4-Cyanobenzyl)-5-imidazolyl } ethyl]-4-carbamoyI- 1 - phenylpiperidine hydrochloride Step A: 4-Cyanobenzyl-N -phthaloylhistamine N^Pivaloyloxymethyl-N^-phthaloylhistamine (4.55 g, 12.8 mmol) was prepared as previously described (J. C. Emmett, F. H. Holloway, and J. L. Turner, J. Chem. Soc, Perkin Trans. J, 1341 , (1979)). α-Bromo-p-tolunitrile (3.77 g, 19.2 mmol) was dissolved in acetonitrile (70 mL). The solution was heated at 55°C for 4 h, cooled to room temperature, and filtered to remove the white solid. The acetonitrile (30 mL) was concentrated to 1/2 its volume under reduced pressure and the solution was heated at 55°C overnight. The solution was cooled and filtered to give a white solid. The volume of the filtrate was reduced to 10 mL, the solution was heated at 55°C for 1 hr, then cooled to room temperature, diluted with ethyl acetate (25 mL) and filtered to obtain additional white solid. The solids were combined, dried, and dissolved in methanol (100 mL) which was saturated with ammonia gas while the temperature was maintained below 30°C. The solution was stirred for 1 hr, concentrated to dryness, and extracted with methylene chloride (3x200 mL), dried (MgSθ4), concentrated, and chromatographed (silica gel, 10:90: 1 MeOH/CH2Cl2/NH4θH) to give the title compound Step B: 4-Cyanobenzyl histamine 4-Cyanobenzyl-N α -phthaloylhistamine (1.64 g, 4.61 mmol), and hydrazine (1.46 mL, 46.1 mmol) were dissolved in absolute ethanol (70 mL). The solution was concentrated after 1 hr and filtered to remove a white precipitate which was washed several times with ethanol. The filtrate was concentrated and the residue was chromatographed (silica gel, 10:90: 1 MeOH/CH2Cl2/NH4θH) to give the title compound. Step C: 4-Carbethox v- 1 -phenylpiperidine A mixture of ethyl isonipecotate (2.00 mL, 12.97 mmol), triphenylbismuth (8.56 g, 19.46 mmol), copper(II)acetate (3.52 g, 19.46 mmol) and triethylamine (2.70 mL, 19.46 mmol) was stirred for 17 h at 20°C in dichloromethane (60 mL). The reaction mixture was adsorbed onto silica gel and eluted with 5% ethyl acetate/hexane. The title compound was obtained as an oil. Step D: 4-Carbox v- 1 -phenylpiperidine The product from Step C was dissolved in methanol and 5% aqueous sodium hydroxide added. After 1 h, methanol was removed in vacuo, and the residue partitioned between ethyl acetate and 10% aqueous HCl. The organic layer was washed with saturated brine, and dried over MgS04. Filtration and concentration provided the title compound. Step E: N-[2-{ 1 -(4-CyanobenzyP-5-imidazolvl lethyll-3-carbamoyl- 1 -phenylpiperidine hydrochloride The product from Step D is dissolved in dimethylformamide. To this solution is added 4-cyanobenzyl histamine dihydrochloride. EDC ■ HCl, and 1-hydroxybenzotriazole. The pH is adjusted to 7.5 with triethylamine. After 16 h, the reaction is poured into water and extracted with ethyl acetate. The organic phase is washed with saturated brine and dried over magnesium sulfate. The crude product is chromatographed on silica gel and the purified product converted to the hydrochloride salt with HCl in methylene chloride. The title compound is isolated by removal of solvent. EXAMPLE 29 4-[2-{ l-(4-Cyanobenzyl)-5-imidazolyl } ethyl]- 1 -phenylpiperidine hydrochloride Step A: 4-Formyl- 1 -phenylpiperidine The product from Example 28, Step C is dissolved in THF and cooled to -78°C under nitrogen. A solution of diisobutylaluminum hydride (1 eq.) in toluene is added dropwise. After 30 min, the reaction is quenched with saturated sodium potassium tartrate solution. The mixture is extracted with ethyl acetate, and the organic phase washed with saturated brine, and dried over MgS04. Filtration and concentration provides the title compound Step B: 4-Hydroxymethyl- 1 -triphenylmethylimidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35.0 g, 260 mmol) in 250 mL of dry DMF at room temperature is added triethylamine (90.6 mL, 650 mmol). A white solid precipitates from the solution. Chlorotriphenylmethane (76.1 g, 273 mmol) in 500 mL of DMF is added dropwise. The reaction mixture is stirred for 20 hours, poured over ice, filtered, and washed with ice water. The resulting product is slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product which is sufficiently pure for use in the next step. Step C: 4-Chloromethyl- 1 -triphenylmethylimidazole The product from Step B is dissolved in chloroform and cooled to 0°C under nitrogen. Thionyl chloride (molar equivalent) is added slowly via syringe. The reaction is stirred for 30 min, and extracted with sodium bicarbonate solution. The organic phase is dried over magnesium sulfate, filtered and concentrated to provide the title compound. Step D: 4-Diethylphosphonomethyl- 1 -triphenylmethylimidazole The product from Step C is dissolved in acetonitrile and cooled to 0°C. Triethyl phosphite ( 1 equivalent) and sodium iodide (1 equivalent) are added, and the reaction stirred at room temperature overnight. The reaction is quenched with ammonium chloride, and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and concentrated to provide the title compound. Step E: 4-[2-{ l -(Triphenylmethyl)-4-imidazolyl }ethenyl]-l- phenylpiperidine The product from Step D is dissolved in THF and cooled to -78°C under nitrogen. A solution of LDA in THF is added dropwise. The reaction was stirred at -78°C for 1 h, then a solution of 4-formyl-l- phenylpiperidine from Step A is added, and the reaction warmed to room temperature overnight. The reaction is quenched with ammonium chloride solution, and extracted with ethyl acetate. The title compound is obtained after chromatography on silica gel. Step F: 4-[2-{ l-(Triphenylmethyl)-4-imidazolyl } ethyl]- 1- phenylpiperidine The product from Step E is dissolved in methanol and hydrogenated at 60 psi hydrogen with 10% palladium on carbon. When reaction is complete, the catalyst is filtered and the title compound obtained after evaporation of solvent. Step G: 4-[2-{ l-(4-Cyanobenzyl)-5-imidazolyl }ethyl]-l- phenylpiperidine hydrochloride The product from Step F is dissolved in acetonitrile and reacted with 4-cyanobenzylbromide (1 equivalent) at room temperature overnight. The reaction is concentrated in vacuo, and the residue dissolved in methanol. The methanol solution is refluxed for 3 h and then concentrated. The residue is partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase is washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The title compound is obtained after purification by silica gel chromatography, and conversion to the dihydrochloride salt. EXAMPLE 30 Preparation of 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)- piperidine- 1 -ylmethyllimidazol- 1 -ylmethyl } benzonitrile Step A: Preparation of Ethyl N-tert-butoxycarbonylpiperidine-4- carboxylate To a cold (0 °C) solution of ethyl isonipecotate (39.5g, 0.251 mol) and triethylamine (38.5 mL, 0.276 mol) in dichloromethane (350 mL), a solution of di-tert-butyl dicarbonate (55.9 g, 0.256 mol) in dichloromethane (50 mL) was added over a period of 30 min. The reacting mixture was stirred at room temp, overnight. The product mixture was washed with aqueous potassium hydrogen sulfate (3 times), and brine (to pH 7). The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the title compound as clear, colorless, viscous oil. Step B: Preparation of Ethyl N-tert-butoxycarbonyl-4-(3-trifluoro- methoxybenzyl)piperidine-4-carboxylate To a cold (-78 °C) solution of ethyl N-tert-butoxycarbonyl- piperidine-4-carboxylate (5.16 g, 20.05 mmol) in anhydrous tetrahydrofuran (60 mL), a solution of sodium bis(trimethylsilyl)amide (28 mL, IM, 28 mmol) was added over a period of 30 min. The resultant mixture was stirred at -78 °C for 1 h, and 3- (trifluoromethoxy)benzyl bromide (5.90 g, 23.14 mmol) was added. The reacting mixture was allowed to warm to room temp, and stirred overnight. The product mixture was concentrated, and the residue was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 20% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step C: Preparation of N-tert-butoxycarbonyl-4-(3-trifluoro- methoxybenzyP-4-hydroxymethyIpiperidine To a slurry of lithium aluminum hydride (585 mg, 15.4 mmol) in anhydrous diethyl ether (100 mL) at 0 °C, a solution of ethyl N-tert-butoxycarbonyl-4-(3-trifluoromethoxybenzyl)piperidine-4- carboxylate (5.84 g, 14.0 mmol) in diethyl ether (30 mL) was added dropwise with the temp, of the reacting mixture maintained below 10 °C. The resulting mixture was stirred at 0 °C for 30 min, and quenched with successive addition of water (0.58 mL), 15% aqueous NaOH (0.58 mL), and water (1.74 mL). The resultant slurry was stirred at room temp, for 30 min., and filtered through a small plug of Celite. The filtrate was washed brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title alcohol. Step D: Preparation of 4-(3-trifluoromethoxybenzyl)-4-hydroxy- methylpiperidine hydrochloride salt A solution of N-tert-butoxycarbonyl-4-(3- trifluoromethoxy-benzyl)-4-hydroxymethylpiperidine (2.9 g) in dichloromethane (100 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was sealed with a rubber septum and stirred at room temp, for 2.5 h. The product solution was concentrated under vacuum to provide the title compound. Step E. Preparation of 4-{5-[4-Hydroxymethyl-4-(3-trifluoro- methoxybenzyPpiperidine- 1 -ylmethyl]imidazol- 1 - ylmethyl I -benzonitrile A mixture of 4-(3-trifluoromethoxybenzyl)-4-hydroxy- methylpiperidine hydrochloride salt (0.62 g, 2.0 mmol), l-(4-cyano- benzyl)imidazole-5-carboxyaldehyde (0.45 g, 2.0 mmol; Example 1, Step E), diisopropylethylamine (0.53 mL, 3.04 mmol), anhydrous magnesium sulfate (650 mg), activated molecular sieves 3 A powder (750 mg), and anhydrous methanol (6 mL) was stirred at room temp, overnight. The pH of the mixture was adjusted to ~5 with addition of glacial acetic acid. To the mixture, a solution of sodium cyanoborohydride in THF (2.2 mL, 1 M, 2.2 mmol) was added slowly over a period of 8 h with a syringe pump, and stirred at room temp, overnight. The product mixture was diluted with chloroform, filtered through Celite. The filtrate was washed with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 5-10% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided the title compound as white solid. Anal. Calcd for C26H27N4O2F3O.38 H2O: C, 63.56; H, 5.69; N, 1 1.40. Found: C, 63.55; H, 5.72; N, 1 1.46. EXAMPLE 31 Preparation of 4-{5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)- piperidine-l-ylmethyll-2-methylimidazol-l -ylmethyl } benzonitrile Step A: Preparation of l-(4-cyanobenzyl)-2-methylimidazole-5- carboxyaldehyde To a cold (0 °C) mixture of 4-formyl-2-methylimidazole (10.0 g, 91 mmol), cesium carbonate (44.4 g, 136 mmol), dimethyl formamide (300 mL) stirred with a mechanical stirred, solid 4- cyanobenzyl bromide (18.7 g, 95 mmol) was added slowly over a period of 5 h using an open end plastic syringe and a syringe pump. The resultant mixture was stirred at 0 °C overnight, concentrated under vacuum. The residue was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was subjected to column chromatography on silica gel eluting with 4% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound as white solid. ] H NMR (CDC13 300MHz) δ 9.67 (IH, s), 7.79 (IH, s), 7.63 (2H, d, J = 8.6 Hz), 7.13 (2H, d, J = 8.6 Hz), 5,62 (2H, s), and 2.42 (3H, s) ppm. Step B: Preparation of 4-{ 5-[4-Hydroxymethyl-4-(3-trifluoro- methoxybenzyl)piperidine-l-ylmethyl]-2-methyIimidazol- 1 - ylmethyl } benzonitrile The title compound was prepared as white solid using the protocol described in Example 30 - Step E, substituting l-(4-cyano- benzyl)imidazole-5-carboxyaldehyde with l-(4-cyanobenzyl)-2- methylimidazole-5-carboxyaldehyde. Anal. Calcd for C27H29N4O2F3: C, 62.05; H, 5.86; N, 11.24. Found: C, 65.06; H, 5.97; N, 11.51. EXAMPLE 32 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(3-trifluoromethylbenzyl)- piperidine- 1 -ylmethyllimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-trifluoromethylbenzyl bromide in Step B. Anal. Calcd for C26H27N4OF3: C, 66.65; H, 5.81; N, 11.96. Found: C, 66.74; H, 5.73; N, 12.38. EXAMPLE 33 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(3-trifluoromethylbenzyl)- piperidine- 1 -ylmethyll-2-methylimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-trifluoromethylbenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5- carboxyaldehyde with l-(4-cyanobenzyl)-2-methylimidazole-5- carboxy aldehyde (Example 31 , Step A) in Step E. Anal. Calcd for C27H29N40F3-2.85 TFA: C, 48.64; H, 3.98; N, 6.94. Found: C, 48.61 ; H, 4.01 ; N, 6.91. EXAMPLE 34 Preparation of 4- { 5-[4-Hydroxymethyl-4-(2-trifluoromethylbenzyl)- piperidine- 1 -ylmethyl]imidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3-(trifluoromethoxy)benzyl bromide with 2- trifluoromethylbenzyl bromide in Step B. Anal. Calcd for C26H27N4OF3O.3O Et2θ: C, 66.57; H, 6.15; N, 1 1.42. Found: C, 66.21 ; H, 5.80; N, 11.22. EXAMPLE 35 Preparation of 4- { 5-[4-Hydroxymethyl-4-(2-methylbenzyl)piperidine- 1 ylmethyllimidazol-1 -ylmethyl } benzonitrile trifluoroacetate salt The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 2-methylbenzyl bromide in Step B. After column chromatography purification, the final product was dissolved in aqueous TFA and lyophilized. Anal. Calcd for C26H30N4O-0.75 TFA-0.05 H2θ: C, 51.90; H, 4.54; N, 7.69. Found: C, 51.89; H, 4.52; N, 7.68. EXAMPLE 36 Preparation of 4- { 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 - ylmethypimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-methylbenzyl bromide in Step B. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C.6H30N4O-0.05 Et2θ-0.25 H2O: C, 74.44; H, 7.39; N, 13.25. Found: C, 74.43; H, 7.31; N, 13.13. EXAMPLE 37 Preparation of 4- { 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 ylmethyl] -2-methy limidazol- 1 -ylmethyl } benzonitrile trifluoroacetate salt The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-methylbenzyl bromide in Step B, and substituting l-(4-cyano-benzyl)imidazole-5-carboxyaldehyde with 1 -(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31 , Step A) in Step E. After column chromatography purification, the final product was dissolved in aqueous TFA and lyophilized. Anal. Calcd for C27H32N40-2.45 TFA- 1.1 H2θ: C, 52.65; H, 5.08; N, 7.70. Found: C, 52.67; H, 5.07; N, 7.79. EXAMPLE 38 Preparation of 4-(5-{2-[4-Hydroxymethyl-4-(3- methylbenzyPpiperidine- l-yl]-2-oxoethyl } imidazol- 1 - ylmethyPbenzonitrile trifluoroacetate salt Step A: Preparation of 4-(3-methylbenzyl)-4- hydroxymethylpiperidine hydrochloride salt The title compound was prepared as white solid according to the procedure described in Example 30, Step B - D substituting 3- (trifluoromethoxy)benzyl bromide with 3-methylbenzyl bromide in Step B. Step B: Preparation of 4-(5-{2-[4-Hydroxymethyl-4-(3- methylbenzyp-piperidine- 1 -yl]-2-oxoethyl } imidazol- 1 - ylmethyPbenzonitrile trifluoroacetate salt A mixture of 4-(3-methylbenzyl)-4- hydroxymethylpiperidine hydrochloride salt (175 mg, 0.52 mmol), 1- (4-cyanobenzyl)imidazole-5-acetic acid-lithium chloride (142 mg, 0.50 mmol), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide-HCl (105 mg, 0.55 mmol), l-hydroxy-7-azabenzotriazole (75 mg, 0.55 mmol), diisopropylethylamine (200 μL, 1.1 mmol) in anhydrous dimethylformamide (2.5 mL) was stirred at room temp, overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C_7H32N4θ-1.65 TFA: C, 57.70; H, 5.06; N, 8.88. Found: C, 57.68; H, 5.20; N, 8.83. EXAMPLE 39 Preparation of 4- { 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 carbon yllimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 38, Step A - B substituting l-(4- cyanobenzyl)imidazole-5-acetic acid-lithium chloride with l-(4- cyanobenzyl)imidazole-5-carboxylic acid in Step B. The crude product was purified with column chromatography on silica gel eluting with 2- 5% methanol in chloroform. Anal. Calcd for C26H28N4O2: C, 72.87; H, 6.59; N, 13.07. Found: C, 72.82; H, 6.67; N, 13.44. EXAMPLE 40 Preparation of 4-{5-[4-Hydroxymethyl-4-(2-methylbenzyl)piperidine-l- carbonyllimidazol- 1 -ylmethyl }benzonitrile The title compound was prepared as white solid according to the procedure described in Example 38, Step A - B substituting l -(4- cyanobenzyl)imidazole-5-acetic acid-lithium chloride with l-(4- cyanobenzyl)imidazole-5-carboxylic acid and 4-(3-methylbenzyl)-4- hydroxymethylpiperidine hydrochloride salt with 4-(2-methylbenzyl)-4- hydroxymethylpiperidine hydrochloride salt (Example 35) in Step B. The crude product was purified with column chromatography on silica gel eluting with 2-5% methanol in chloroform. Anal. Calcd for C26H28N4O2: C, 72.87; H, 6.59; N, 13.07. Found: C, 72.82; H, 6.67; N, 13.44. EXAMPLE 41 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(3-chlorobenzyl)-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-chlorobenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxyaldehyde with l-(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31, Step A) in Step E. Anal. Calcd for C26H29N4OC1-0.20 H2θ: C, 69.00; H, 6.55; N, 12.38. Found: C, 68.96; H, 6.78; N, 12.49. EXAMPLE 42 Preparation of 4- { 5-[4-Hydroxymethyl-4-(2-cyanobenzyl)-piperidine- 1 - ylmethyl]-2-methylimidazol- 1 -ylmethyl }benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 2-cy anobenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxy aldehyde with 1 -(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31 , Step A) in Step E. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C27H29N5O-0.05 H2O-0.05 Et2θ: C, 73.55; H, 6.72; N, 15.77. Found: C, 73.51 ; H, 6.55; N, 15.75. EXAMPLE 43 Preparation of 4- { 5-[4-Hydroxymethyl-4-(3-cyanobenzyl)-ρiperidine- 1 ylmethyl1-2-methylimidazol-1 -ylmethyl l benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3-cyanobenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxyaldehyde with l-(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31, Step A) in Step E. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C27H29N5O-0.35 H2O-0.5 Et2θ: C, 72.12; H, 7.24; N, 14.50. Found: C, 72.13; H, 6.99; N, 14.47. EXAMPLE 44 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(4-cyanobenzyl)piperidine- 1 - ylmethyll-2-methylimidazol-l-ylmethvUbenzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 4-cyanobenzyl bromide in Step B, and substituting l-(4-cyano-benzyl)imidazole-5-carboxy aldehyde with 1 -(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31, Step A) in Step E. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C27H29N5O-0.1 H2O-0.25 Et2θ: C, 73.12; H, 6.95; N, 15.23. Found: C, 73.14; H, 6.83; N, 15.23. EXAMPLE 45 Preparation of 4-{5-14-Hydroxymethyl-4-(2,5- dimethy IbenzyPpiperidine- 1 -ylmethyl]-2-methylimidazol- 1 - ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3-(trifluoromethoxy)benzyl bromide with 2,5- dimethylbenzyl bromide in Step B, and substituting l-(4- cyanobenzyl)imidazole-5-carboxyaldehyde with 1 -(4-cyanobenzyl)-2- methylimidazole-5-carboxyaldehyde (Example 31, Step A) in Step E. Anal. Calcd for C28H34N4O-0.1 H2θ: C, 75.68; H, 7.76; N, 12.61. Found: C, 75.62; H, 7.65; N, 12.60. EXAMPLE 46 Preparation of 4-{5-[4-Hydroxymethyl-4-(2,5- dichlorobenzyPpiperidine- 1 -ylmethyl]-2-methylimidazol- 1 - ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 2,5-dichlorobenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxy aldehyde with l-(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31 , Step A) in Step E. Anal. Calcd for C26H28N4OCI2: C, 64.60; H, 5.84; N, 11.59. Found: C, 65.33; H, 5.70; N, 11.85. EXAMPLE 47 Preparation of 4-{5-L4-Hydroxymethyl-4-(3,5- dimethylbenzyPpiperidine- 1 -ylmethyl]-2-methy limidazol- 1 - ylmethyl 1 benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3,5-dimethylbenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxyaldehyde with l-(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31 , Step A) in Step E. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C28H34N4OO.I4 Et2θ: C, 75.73; H, 7.88; N, 12.37. Found: C, 75.70; H, 7.88; N, 12.39. EXAMPLE 48 Preparation of 4-(5-{4-Hydroxymethyl-4-[3,5- bis(trifluoromethyl)benzyl]-piperidine- 1 -ylmethyl } -2-methylimidazol-_: ylmethyPbenzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 3,5-bis(trifιuoromethyl)benzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5- carboxyaldehyde with l-(4-cyanobenzyI)-2-methylimidazole-5- carboxyaldehyde (Example 31, Step A) in Step E. After column chromatography purification, the final product was triturated in diethyl ether, filtered, and dried under vacuum overnight. Anal. Calcd for C28H34N4OO.I4 Et2θ: C, 61.01 ; H, 5.42; N, 9.81. Found: C, 61.01; H, 5.12; N, 9.58. EXAMPLE 49 Preparation of 4-{5-[4-Hydroxymethyl-4-(2,3- dichlorobenzy Ppiperidine- 1 -ylmethyl] -2-methy limidazol- 1 • ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with 2,3-dichlorobenzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxyaldehyde with 1 -(4-cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31, Step A) in Step E. Anal. Calcd for C26H28N4OCl2 » 0.2 H2O-0.05 MeOH: C, 64.03; H, 5.90; N, 11.47. Found: C, 64.04; H, 5.95; N, 11.75. EXAMPLE 50 Preparation of 4-[5-(4-Hydroxymethyl-4-benzylpiperidine- 1 -ylmethyl)- 2-methylimidazol- 1 -ylmethyllbenzonitrile The title compound was prepared as white solid according to the procedure described in Example 30, Step B - E substituting 3- (trifluoromethoxy)benzyl bromide with benzyl bromide in Step B, and substituting l-(4-cyanobenzyl)imidazole-5-carboxyaldehyde with l-(4- cyanobenzyl)-2-methylimidazole-5-carboxyaldehyde (Example 31 , Step A) in Step E. Anal. Calcd for C26H28N4OCI2: C, 75.00; H, 7.31; N, 13.46. Found: C, 75.06; H, 7.20; N, 13.43. EXAMPLE 51 Preparation of 4- { 5-[4-Hydroxymethy l-4-(3-trifluoromethoxybenzyl)- piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl jbenzamide A solution of 4-{5-[4-hydroxymethyl-4-(3- trifluoromethoxy-benzyl)-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 - ylmethyl} benzonitrile (71 mg, 0.142 mmol; Example 31) and sodium perborate tetrahydrate (92.8 mg, 0.6 mmol) in a mixture of methanol (2.5 mL) and water (1 mL) was heated at 50 °C for 7 h. The resultant mixture was concentrated under vacuum, and the residue was partitioned between chloroform and dilute hydrochloric acid (0.5 M). The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H31N4O3F3O.25 H2θ: C, 62.24; H, 6.09; N, 10.75. Found: C, 62.20; H, 6.05; N, 11.04. FAB MS m/e 517 (M+l) EXAMPLE 52 Preparation of 4-{ 5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine- l-ylmethyl]imidazol-l -ylmethyl } benzonitrile hydrochloride salt Step A: Preparation of N-tert-butoxycarbonyl-4-(3-methylbenzyl)- 4-hydroxymethylpiperidine The title compound was prepared using the protocol described in Example 30, Step A - C, substituting 3- (trifluoromethoxy)benzyl bromide with 3-methylbenzyl bromide in Step B. Step B: Preparation of N-tert-butoxycarbonyl-4-(3-methylbenzyl)- 4-methoxymethylpiperidine To a suspension of potassium hydride (0.40 g, dry weight, 10 mmol; obtained from washing 0.97 g of 35% potassium hydride dispersion in mineral oil with hexanes and drying under a stream of argon) in anhydrous THF (45 mL), N-tert-butoxycarbonyl-4-(3- methylbenzyl)-4-hydroxymethylpiperidine (1.89 g, 5.9 mmol) in THF (15 mL) was added. The resultant mixture was stirred at room temp, for 1 h, and treated with dimethyl sulfate (1.13 mL, 11.9 mmol). The reacting mixture was stirred at room temp, overnight. The product mixture was cooled to 0 °C, quenched with water, and diluted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step C: Preparation of 4-(3-methylbenzyl)-4-methoxymethyl- piperidine hydrochloride salt To a cold (0 °C) solution of N-tert-butoxycarbonyl-4-(3- methylbenzyl)-4-methoxymethylpiperidine (1.95 g) in ethyl acetate (100 mL), a stream of anhydrous hydrogen chloride gas was bubbled for 20 min. The resultant mixture was stirred at 0 °C for 1 h, purged with argon for 20 min., and concentrated under vacuum to provide the title compound as white solid. Step D: Preparation of l-(4-cyanobenzyl)-5-chloromethylimidazole hydrochloride salt A mixture of l-(4-cyanobenzyl)-5-hydroxymethylimidazole (10.8 g, 50.70 mmol; Example 1, Step D) and thionyl chloride (70 mL, 960 mmol) was stirred at room temp, overnight under a calcium chloride drying tube. The resultant mixture was concentrated under vacuum, and residual thionyl chloride was removed by co-evaporation with toluene. The residue was recrystallized from boiling methanol. After cooling to room temp., the white solid precipitated was obtained by filtration, and residual solvent was removed under vacuum overnight. Step E: Preparation of 4-{5-[4-Methoxymethyl-4-(3-methylbenzyl)- piperidine- 1 -ylmethylfimidazol- 1 -ylmethyl Ibenzonitrile hydrochloride salt A solution of 4-(3-methylbenzyl)-4- methoxymethylpiperidine hydrochloride salt (1.57 g, 5.8 mmol), l-(4- cyanobenzyl)-5-chloromethyl-imidazole hydrochloride salt (1.57 g, 5.8 mmol), and diisopropylethyl-amine (5.1 mL, 29 mmol) in anhydrous acetonitrile (75 mL) was heated at 60 °C overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 3% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound as free base. The free base obtained was dissolved in anhydrous diethyl ether (50 mL), cooled to 0 °C, and bubbled with anhydrous hydrogen chloride gas for 20 second. The resultant mixture was concentrated, and the residue solid recrystallized from a mixture of methanol and diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound. Anal. Calcd for C27H32N40-2 HC1-0.70 H2θ: C, 63.08; H, 6.94; N, 10.90. Found: C, 63.06; H, 6.91; N, 10.95. EXAMPLE 53 Preparation of 4-{5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine- 1 -ylmethyll-2-methy limidazol- 1 -ylmethyl } benzonitrile Step A: Preparation of l-(4-cyanobenzyl)-5-hydroxymethyl-2- methylimidazole A solution of l-(4-cyanobenzyl)-2-methylimidazole-5- carboxyaldehyde (4.0 g, 17.76 mmol; Example 31, Step A) in methanol (85 mL) at room temp, was treated with sodium borohydride (0.52 g, 13.7 mmol; added in two portions, 10 min. apart). After stirring at room temp, for 30 min., the resultant slurry was concentrated to about 15 mL. The white solid precipitated was filtered, washed with anhydrous diethyl ether, and residual solvent was removed under vacuum to provide the title compound. Step B: Preparation of l-(4-cyanobenzyl)-5-chloromethyl-2- methylimidazole hydrochloride salt A mixture of l-(4-cyanobenzyl)-5-hydroxymethyl-2- methy limidazole (3.45 g, 15.2 mmol) and thionyl chloride (30 mL, 411 mmol) was stirred at room temp, overnight under a calcium chloride drying tube. The resultant mixture was concentrated under vacuum, and residual thionyl chloride was removed by co-evaporation with toluene. The residue was triturated with anhydrous diethyl ether, filtered, washed with ether to provide the title compound as white solid. Step C: Preparation of 4- { 5-[4-Methoxymethyl-4-(3-methylbenzyl)- piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl } - benzonitrile The title compound was prepared using the protocol described in Example 52, Step E substituting 1 -(4-cyanobenzyl)-5- chloromethyl-imidazole hydrochloride salt with l-(4-cyanobenzyl)-5- chloromethyl-2-methylimidazole hydrochloride salt. After column chromatography purification, collection and concentration of appropriate fractions, the residue was triturated with anhydrous diethyl ether. The white solid precipitated was obtained by filtration and provided the title compound. Anal. Calcd for C28H34N4O-0.15 Et2θ -0.50 H2θ: C, 74.24; H, 7.95; N, 12.11. Found: C, 74.22; H, 7.59; N, 12.13. EXAMPLE 54 Preparation of 4- { 5-[4-Methoxymethyl-4-(3-trifluoromethoxybenzyl)- piperidine- 1 -ylmethyl]imidazol- 1 -ylmethyl } benzonitrile hydrochloride salt The title compound was prepared using the protocol described in Example 30, Step A - C using 3-(trifluoromethoxy)benzyl bromide in Step B, and in Example 52, Step B - E substituting N-tert- butoxycarbonyl-4-(3-methylbenzyl)-4-hydroxymethylpiperidine with N- tert-butoxy-carbonyl-4-(3-trifluoromethoxybenzyl)-4- hydroxy methy lpiperidine in Step B. Anal. Calcd for C27H29N4θ2F3*2.6 HCl: C, 54.66; H, 5.37; N, 9.44. Found: C, 54.69; H, 5.37; N, 9.42. EXAMPLE 55 Preparation of 4-{5-[4-Methoxymethyl-4-(3-trifluoromethoxybenzyl)- piperidine- l-ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile hydrochloride salt The title compound was prepared using the protocol described in Example 30, Step A - C using 3-(trifluoromethoxy)benzyl bromide in Step B, and in Example 52, Step B - E substituting N-tert- butoxycarbonyl-4-(3-methylbenzyl)-4-hydroxymethylpiperidine with N- tert-butoxy-carbonyl-4-(3-trifluoromethoxybenzyl)-4- hydroxymethylpiperidine in Step B, and substituting l-(4-cyanobenzyl)- 5-chloromethyl-imidazole hydro-chloride salt with l-(4-cyanobenzyl)-5- chloromethyl-2-methylimidazole hydrochloride salt in Step E. Anal. Calcd for C28H3lN4θ2F3 « 2.2 HCl: C, 56.73; H, 5.65; N, 9.45. Found: C, 56.79; H, 5.39; N, 9.40. EXAMPLE 56 Preparation of 4-{5-[4-Methoxymethyl-4-(2-trifluoromethoxybenzyl)- piperidine- 1 -ylmethyl]imidazol- 1 -ylmethyl } benzonitrile hydrochloride salt The title compound was prepared using the protocol described in Example 30, Step A - C using 2-(trifluoromethoxy)benzyl bromide in Step B, and in Example 52, Step B - E substituting N-tert- butoxycarbonyl-4-(3-methylbenzyl)-4-hydroxymethylpiperidine with N- tert-butoxy-carbonyl-4-(2-trifluoromethoxybenzyl)-4- hy droxy methylpiperidine in Step B. Anal. Calcd for C27H29N4θ2F « 2.45 HC1-0.20 Et2θ: C, 55.40; H, 5.59; N, 9.30. Found: C, 55.38; H, 5.52; N, 9.20. EXAMPLE 57 Preparation of 4-{ 5-[4-Methoxymethyl-4-(2-trifluoromethoxybenzyl)- piperidine- 1 -ylmethyl]-2-methy limidazol- 1 -ylmethyl } benzonitrile hydrochloride salt The title compound was prepared using the protocol described in Example 30, Step A - C using 2-(trifluoromethoxy)benzyl bromide in Step B, and in Example 52, Step B - E substituting N-tert- butoxycarbonyl-4-(3-methylbenzyl)-4-hydroxymethylpiperidine with N- tert-butoxy-carbonyl-4-(2-trifluoromethoxybenzyl)-4- hydroxymethylpiperidine in Step B, and substituting l-(4-cyanobenzyl)- 5-chloromethyl-imidazole hydro-chloride salt with l-(4-cyanobenzyl)-5- chloromethyl-2-methylimidazole hydrochloride salt in Step E. Anal. Calcd for C28H3 lN4θ2F3*2.6 HCl: C, 55.37; H, 5.58; N, 9.22. Found: C, 55.38; H, 5.52; N, 9.20. EXAMPLE 58 Preparation of 4-{5-[4-Methoxymethyl-4-(3-cyanobenzyl)-piperidine-l ■ ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 30, Step A - C using 3-cyanobenzyl bromide in Step B, and in Example 52, Step B - E substituting N-tert- butoxycarbonyl-4-(3-methyl-benzyl)-4-hydroxymethylpiperidine with N-tert-butoxycarbonyl-4-(3-cyanobenzyl)-4-hydroxymethylpiperidine in Step B, and substituting l-(4-cyanobenzyl)-5-chloromethyl-imidazole hydrochloride salt with l-(4-cyanobenzyl)-5-chloromethyl-2- methylimidazole hydrochloride salt in Step E. The crude product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C_8H3 lN5θ-2 TFA: C, 56.39; H, 4.88; N, 10.27. Found: C, 56.04; H, 5.06; N, 10.26. EXAMPLE 59 Preparation of 4-(5-{2-[4-Methoxymethyl-4-(3-methylbenzyl)- piperidine- 1 -y l]-2-oxoethyl } imidazol- 1 -ylmethyl)benzonitrile trifluoroacetate salt The title compound was prepared according to the procedure described in Example 38, Step B substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(3- methylbenzyl)-4-methoxymethylpiperidine hydrochloride salt (Example 52, Step C). The crude product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C28H32N4θ2 « 1.7 TFA: C, 57.98; H, 5.22; N, 8.61. Found: C, 57.93; H, 5.30; N, 8.67. EXAMPLE 60 Preparation of 4- { 5-[4-Methoxymethyl-4-(3-methylbenzyl)piperidine- 1 carbonyllimidazol- 1 -ylmethyl } benzonitrile trifluoroacetate salt The title compound was prepared according to the procedure described in Example 38, Step B substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(3- methylbenzyl)-4-methoxymethylpiperidine hydrochloride salt (Example 52, Step C), and l-(4-cyanobenzyI)imidazole-5-acetic acid-lithium chloride with l-(4-cyanobenzyl)imidazole-5-carboxylic acid. The crude product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C_7H3θN4θ-1.2 TFA-1.1 H2θ: C, 58.93; H, 5.62; N, 9.35. Found: C, 58.90; H, 5.41 ; N, 9.74. EXAMPLE 61 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (3-methylbenzyl)piperidine-4-carboxylate Step A: Preparation of Methyl N-tert-butoxycarbonyl-4-(3-methyl- benzyl)piperidine-4-carboxy1ate To a cold (-78 °C) solution of methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate (5.0 g, 20.5 mmol; Example 3, Step B) in anhydrous THF (70 mL), a solution of sodium bis(trimethylsilyl)amide (20.5 mL, IM, 20.5 mmol) was added over a period of 30 min. The resultant mixture was stirred at -78 °C for 1 h., and 3 -methy lbenzy 1 bromide (2.77 mL, 20.5 mmol) was added. The reacting mixture was allowed to warm up to room temp, and stirred overnight. The product mixture was concentrated, and the residue was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of Methyl 4-(3-methylbenzyl)piperidine-4- carboxylate hydrochloride salt To a cold (0 °C) solution of methyl N-tert-butoxycarbonyl- 4-(3-methylbenzyl)piperidine-4-carboxylate (1.14 g) in ethyl acetate (75 mL), a stream of anhydrous hydrogen chloride gas was bubbled for 20 min. The resultant mixture was stirred at 0 °C for 1 h, purged with argon for 10 min., and concentrated under vacuum to provide the title compound as white solid. Step C: Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4 ylmethyll-4-(3-methylbenzyPpiperidine-4-carboxylate A solution of methyl 4-(3-methylbenzyl)piperidine-4- carboxylate hydrochloride salt (142 mg, 0.5 mmol), l -(4-cyanobenzyl)- 5-chloromethylimidazole hydrochloride salt (135 mg, 0.5 mmol; Example 52, Step D), and diisopropylethylamine (0.26 mL, 1.5 mmol) in anhydrous acetonitrile (5 mL) was heated under reflux overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 5% methanol in chloroform. After collection and concentration of appropriate fractions, the residue was recrystallized from a mixture of ethyl acetate and hexane to provide the title compound as white solid. Anal. Calcd for C27H30N4O2O.2 Hexane: C, 73.66; H, 7.19; N, 12.18. Found: C, 73.68; H, 6.84; N, 11.79. EXAMPLE 62 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (3-trifluoromethoxybenzyPpiperidine-4-carboxylate trifluoroacetate salt The title compound was prepared using the protocol described in Example 61, Step A - C substituting 3-methylbenzyl bromide with 3-trifluoromethoxybenzyl bromide in Step A. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H27N4θ3F3-2.35 TFA -1.05 H2θ: C, 47.62; H, 3.97; N, 7.01. Found: C, 47.61 ; H, 4.10; N, 6.61. EXAMPLE 63 Preparation of Methyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4- ylmethyl]-4-(3-trifluoromethoxybenzyl)piperidine-4-carboxylate trifluoroacetate salt The title compound was prepared using the protocol described in Example 61, Step A - C substituting 3-methy lbenzy 1 bromide with 3-trifluoromethoxybenzyl bromide in Step A, and substituting l-(4-cyano-benzyl)-5-chloromethylimidazole hydrochloride salt with 1 -(4-cyano-benzyl)-5-chloromethyl-2-methylimidazole hydrochloride salt (Example 53, Step B) in Step C. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C28H29N4θ3F3'2.3 TFA -1.05 H2θ: C, 48.47; H, 4.17; N, 6.94. Found: C, 48.48; H, 4.19; N, 6.91. EXAMPLE 64 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (2-trifluoromethoxybenzyl)piperidine-4-carboxylate trifluoroacetate salt The title compound was prepared using the protocol described in Example 61, Step A - C substituting 3-methylbenzyl bromide with 2-trifluoromethoxybenzyl bromide in Step A. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H27N4O3F3-2.50 TFA -2.30 H2O: C, 45.81 ; H, 4.10; N, 6.68. Found: C, 46.11; H, 3.89; N, 6.28. EXAMPLE 65 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (3-cyanobenzyl)piperidine-4-carboxylate hydrochloride salt The title compound was prepared using the protocol described in Example 61 , Step A - C substituting 3-methylbenzyl bromide with 3-cyanobenzyl bromide in Step A. After column chromatography on silica gel, the free base obtained was dissolved in anhydrous diethyl ether. The ethereal solution was cooled to 0 °C, and bubbled with anhydrous hydrogen chloride gas for 20 second. The resultant mixture was concentrated, and the residue solid recrystallized from a mixture of methanol and diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound. Anal. Calcd for C27H27N5θ2 « 2.35 HCl- 1.80 MeOH: C, 57.95; H, 6.17; N, 1 1.73. Found: C, 57.94; H, 6.16; N, 1 1.72. EXAMPLE 66 Preparation of Methyl l-[3-(4-cyanobenzy])-3H-imidazol-4-ylmethyl]-4- 3-(benzyloxycarbonylaminomethyPbenzyllpiperidine-4-carboxylate Step A: Preparation of Methyl N-tert-butoxycarbonyl-4-(3-cyano- benzyl)piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61 , Step A substituting 3-methylbenzyl bromide with 3-cyanobenzyl bromide. Step B: Preparation of Methyl N-tert-butoxycarbonyl-4-(3-amino- methylbenzyl)piperidine-4-carboxylate A mixture of methyl N-tert-butoxycarbonyl-4-(3-cyano- benzyl)piperidine-4-carboxylate (0.6 g, 1.67 mmol), Raney nickel (3 g) in a mixture of ethanol (20 mL) and concentrated aqueous ammonium hydroxide (0.6 mL) was stirred under a balloon of hydrogen gas at room temp, overnight. The slurry was filtered, and the filtrate concentrated under vacuum to provide the title compound. Step C: Preparation of Methyl N-tert-butoxycarbonyl-4-[3-(benzyl- oxycarbonylaminomethyPbenzyllpiperidine-4-carboxylate A mixture of methyl N-tert-butoxycarbonyl-4-(3-amino- methylbenzyl)piperidine-4-carboxylate (1.67 mmol), benzyl chloroformate (0.48 mL, 3.36 mmol), and diisopropylethylamine (1 mL, 5.74 mmol) in dichloromethane was stirred at room temp.. The resultant solution was diluted with dichloromethane, washed with aqueous sodium bicarbonate, and then brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 40% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound as clear colorless gum. Step D: Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-13-(benzyloxycarbonylaminomethyl)benzyll- piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61 , Step B - C substituting methyl N-tert- butoxycarbonyl-4-(3-methylbenzyl)piperidine-4-carboxylate with methyl N-tert-butoxycarbonyl-4-[3-(benzyloxycarbonylaminomethyl)- benzyl]piperidine-4-carboxylate in Step B. After column chromatography on silica gel, the free base obtained was triturated with a mixture of dichloromethane and diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound. Anal. Calcd for C35H37N5O4O.2 E-2O-0.05 CH2CI2: C, 70.50; H, 6.45; N, 1 1.47. Found: C, 70.39; H, 6.17; N, 1 1.46. EXAMPLE 67 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- [3-(aminomethyl)benzyl]piperidine-4-carboxylate trifluoroacetate salt A mixture of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-[3-(benzyloxycarbonylaminomethyl)benzyl]-piperidine-4- carboxylate (0.13 g, 0.22 mmol; Example 66, Step D) and 30% hydrobromide in acetic acid (4 mL) was stirred at room temp, for 30 min. The resultant mixture was concentrated under vacuum. The residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H3lN5θ2 « 3.35 TFA- 1.05 H2O: C, 47.15; H, 4.28; N, 8.16. Found: C, 47.15; H, 4.24; N, 8.88. EXAMPLE 68 Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4- ylmethyl]-4-[3-(methanesulfonylaminomethyl)benzyl]piperidine-4- carboxylate Step A: Preparation of Ethyl N-tert-butoxycarbonyl-4-(3-amino- methylbenzyPpiperidine-4-carboxylate The title compound was prepared using the protocol described in Example 66, Step A - B substituting methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate with ethyl N-tert- butoxycarbonyl-piperidine-4-carboxylate (Example 30, Step A). Step B: Preparation of Ethyl N-tert-butoxycarbonyl-4-[3-(methane- sulfonylaminomethyl)benzyllpiperidine-4-carboxylate A mixture of ethyl N-tert-butoxycarbonyl-4-(3-amino- methylbenzyl)piperidine-4-carboxylate (400 mg, 0.106 mmol) and methanesulfonyl chloride (99 μL, 0.127 mmol) in anhydrous pyridine (4 mL) was heated at 70 °C for 4 h. The resultant mixture was concentrated, and the residue was subjected to column chromatography on silica gel eluting with 50% ethyl acetate in hexane. Collection and concentration of appropriate fraction provided the title compound. Step C: Preparation of Ethyl 4-[3-(methanesulfonylaminomethyl)- benzyllpiperidine-4-carboxylate hydrochloride salt A solution of ethyl N-tert-butoxycarbonyl-4-[3-(methane- sulfonylaminomethyl)benzyl]piperidine-4-carboxylate (270 mg) in dichloromethane (40 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was sealed with a rubber septum and stirred at room temp, for 2.5 h. The product solution was concentrated under vacuum to provide the title compound Step D: Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H- imidazol-4-ylmethyl]-4-[3-(methanesulfonylaminome benzyl]piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61, Step C substituting methyl 4-(3- methylbenzyl)piperidine-4-carboxylate hydrochloride salt with ethyl 4- [3-(methanesulfonylamino-methyl)benzyl]piperidine-4-carboxylate hydrochloride salt, and l-(4-cyanobenzyl)-5-chloromethylimidazole hydrochloride salt with l -(4-cyanobenzyl)-5-chloromethyl-2- methylimidazole hydrochloride salt (Example 53, Step B). After column chromatography on silica gel, the free base obtained was triturated with anhydrous diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound. Anal. Calcd for C30H37N5O4 OS-0.2 Et2θ-0.3 H2O: C, 63.35; H, 6.84; N, 11.99. Found: C, 63.34; H, 6.71 ; N, 1 1.99. EXAMPLE 69 Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4- ylmethyll-4-(3-nitrobenzyPpiperidine-4-carboxylate Step A: Preparation of Ethyl N-tert-butoxycarbonyl-4-(3- nitrobenzyl)piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61 , Step A substituting methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate with ethyl N-tert- butoxycarbonyl-piperidine-4-carboxylate (Example 30, Step A), and 3- methylbenzyl bromide with 3-nitrobenzyl bromide. Step B: Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H- imidazol-4-ylmethyl]-4-(3-nitrobenzyl)piperidine-4- carboxylate The title compound was prepared using the protocol described in Example 61 , Step B - C substituting methyl N-tert- butoxycarbonyl-4-(3-methylbenzyl)piperidine-4-carboxylate with ethyl N-tert-butoxycarbonyl-4-(3-nitrobenzyl)piperidine-4-carboxylate in Step B, and l-(4-cyano-benzyl)-5-chloromethylimidazole hydrochloride salt with l-(4-cyano-benzyl)-5-chloromethyl-2-methylimidazole hydrochloride salt (Example 53, Step B) in Step C. Anal. Calcd for C28H3iN5O.4-O.45 CHCI3: C, 61.54; H, 5.71; N, 12.61. Found: 61.39; H, 5.56; N, 12.74. EXAMPLE 70 Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4- ylmethyll-4-(3-methanesulfonylaminobenzyl)piperidine-4-carboxylate Step A: Preparation of Ethyl N-tert-butoxycarbonyl-4-(3-methane- sulfonylaminobenzyl)piperidine-4-carboxylate A mixture of ethyl N-tert-butoxycarbonyl-4-(3- nitrobenzyl)-piperidine-4-carboxylate (0.85 g, 2.17 mmol; Example 69, Step A) and 5% palladium on charcoal (0.06 g) in ethanol ( 100 mL) was hydrogenated at room temp, at 50 psi overnight. The resultant mixture was filtered through a plug of Celite, and the filtrate was concentrated under vacuum. The residue was dissolved in pyridine (5 mL), treated with methanesulfonyl chloride (0.24 mL, 3.2 mmol), and heated at 60 °C for 3 h. The product mixture was concentrated under vacuum, and the residue was subjected to column chromatography on silica gel eluting with 2% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H- imidazol-4-ylmethyl]-4-(3-methanesulfonylaminobenzyl)- piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 69, Step B substituting ethyl N-tert- butoxycarbonyl-4-(3-nitrobenzyl)piperidine-4-carboxylate with ethyl N- tert-butoxycarbonyl-4-(3-methanesulfonylaminobenzyl)piperidine-4- carboxylate. Anal. Calcd for C29H35N5O4S-0.05 CHCI3: C, 62.79; H, 6.36; N, 12.60. Found: 62.87; H, 6.24; N, 12.76. EXAMPLE 71 Preparation of Ethyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- benzylpiperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61, Step A - C substituting methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate with ethyl N-tert- butoxycarbonyl-piperidine-4-carboxylate, and 3-methylbenzyl bromide with benzyl bromide. Anal. Calcd for C27H30N4O20.1 CHCI3O. I H2O: C, 71.33; H, 6.69; N, 12.28. Found: 71.35; H, 6.62; N, 12.40. EXAMPLE 72 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- cyclopropylmethylpiperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61, Step A - C substituting 3 -methy lbenzy 1 bromide with cyclopropylmethyl bromide. Anal. Calcd for C23H28N4O2: C, 70.38; H, 7.19; N, 14.27. Found: 70.41 ; H, 7.13; N, 14.28. EXAMPLE 73 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]- 4-(3-methylbenzyl)piperidine-4-carboxylate The title compound was prepared according to the procedure described in Example 38, Step B substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt (Example 61 , Step B), and l-(4-cyanobenzyl)imidazole-5-acetic acid-lithium chloride with l-(4-cyanobenzyl)imidazole-5-carboxylic acid. Anal. Calcd for C27H28N4O3: C, 71.03; H, 6.18; N, 12.27. Found: C, 71.10; H, 6.27; N, 12.26. EXAMPLE 74 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]- 4-(2-methylbenzvPpiperidine-4-carboxylate The title compound was prepared according to the procedure described in Example 73, using methyl 4-(2- methylbenzyl)piperidine-4-carboxylate hydrochloride salt (Example 61). Anal. Calcd for C27H28N4O3O.O5 Et2θ: C, 70.98; H, 6.24; N, 12.17. Found: C, 71.08; H, 6.62; N, 12.49. EXAMPLE 75 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4- (3-trifluoromethoxybenzyl)piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 61 , Step A - B substituting 3-methylbenzyl bromide with 3-trifluoromethoxybenzyl bromide in Step A, and in Example 38, Step B substituting 4-(3-methylbenzyl)-4- hydroxymethylpiperidine hydrochloride salt with methyl 4-(3- trifluoromethoxybenzyl)piperidine-4-carboxylate hydrochloride salt. The final product was subjected to high pressure liquid column chromatography on C- 18 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C28H27N4θ4F3*1.2 TFA- 1.0 H2θ: C, 52.50; H, 4.38; N, 8.06. Found: C, 52.51; H, 4.41; N, 7.99. EXAMPLE 76 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4- (2-trifluoromethoxybenzyPpiperidine-4-carboxylate The title compound was prepared according to the procedure described in Example 75, using 3-trifluoromethoxybenzyl bromide. Anal. Calcd for C28H27N4θ4F3 « 1.5 TFA- 1.7 H2O: C, 50.16; H, 4.33; N, 7.55. Found: C, 50.20; H, 4.35; N, 7.38. EXAMPLE 77 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4- (3-cyanobenzyl)piperidine-4-carboxylate The title compound was prepared according to the procedure described in Example 75, using 3-cyanobenzyl bromide. Anal. Calcd for C28H27N5θ3 β 1.9 HC1-0.6 toluene: C, 63.80; H, 5.60; N, 1 1.56. Found: C, 63.83; H, 5.91; N, 11.57. EXAMPLE 78 Preparation of methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl]-4- (3-methylbenzyPpiperidine-4-carboxylate To a cold (-78 °C) solution of 3-(4-cyanobenzyl)-3H- imidazol-4-ylethyl alcohol (184 mg, 0.81 mmol) and diisopropylethylamine (155 μL, 0.89 mmol) in dichloromethane (3.8 mL), trifluoromethanesulfonic anhydride ( 143 μL, 0.85 mmol) was added. The resulting mixture was stirred at -78 °C for 20 min., and was treated with a solution of methyl 4-(3-methylbenzyl)piperidine-4- carboxylate hydrochloride salt (276 mg, 0.97 mmol; Example 61, Step B) and diisopropylethylamine (186 μL, 1.07 mmol) in dichloromethane (1 mL). The reaction mixture was stirred at -78 °C for one h., and at room temp, for two h. The resultant solution was concentrated under vacuum, and the residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C28H- 32N4θ2 β 2.75 TFA: C, 52.25; H, 4.55; N, 7.27. Found: C, 52.28; H, 4.66; N, 7.24. EXAMPLE 79 Preparation of (±) Methyl 2-(n-butyl)-l-[3-(4-cyanobenzyl)-3H- imidazol-4-ylmethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate trifluoroacetate salt Step A: Preparation of Methyl 2-(n-but- l -ynyl)pyridine-4- carboxylate A mixture of methyl 2-chloropyridine-4-carboxylate (3.32 g, 19.3 mmol), bis(triphenylphosphine)palladium(II) chloride (0.82 g, 1.1 mmol), copper(I) iodide (0.36 g, 1.9 mmol), triethylamine (30 mL), and n-but-1 -yne (-5 g) was heated in a sealed tube at 80 °C overnight. The product mixture was concentrated, and the residue was subjected to column chromatography on silica gel eluting with chloroform. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of Methyl N-tert-butoxycarbonyl-2-(n-butyl)- piperidine-4-carboxylate A mixture of methyl 2-(n-but-l-ynyl)pyridine-4- carboxylate (3.0 g, 15.8 mmol) and platinum (IV) oxide (0.3 g) in methanol (300 mL) acidified with anhydrous hydrochloride gas (-2%) was hydrogenated at room temp, at 55 psi overnight. The resultant mixture was filtered through a plug of Celite, and the filtrate was concentrated under vacuum. The residue was dissolved in mixture of diisopropylethylamine (6.9 mL, 39 mmol) and dichloromethane (60 mL), and treated with di-tert-butyl dicarbonate (4.1g, 19 mmol). The reaction mixture was stirred at room temp, overnight. The product mixture was concentrated and the residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 15% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step C: Preparation of (±) Methyl 2-(n-butyl)-l-[3-(4- cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyPρiperidine-4-carboxylate trifluoroacetate salt The title compound was prepared using the protocol described in Example 61, Step A - C substituting methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate with methyl N-tert- butoxycarbonyl-2-(n-butyl)-piperidine-4-carboxylate in Step A. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C3lH38N4θ2 « 2.25 TFA -0.95 H2θ: C, 55.21 ; H, 5.50; N, 7.25. Found: C, 55.21 ; H, 5.52; N, 7.44. EXAMPLE 81 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyPisonipecotamide Step A: Preparation of N-tert-butoxycarbonylisonipecotic acid To a solution of isonipecotic acid (25.8 g, 200 mmol) in 1 M aqueous sodium hydroxide (223 mL, 223 mmol), a solution of di- tert-butyl dicarbonate in tetrahydrofuran (200 mL) was added over a period of one h. The resulting solution was stirred at room temp. overnight. The reaction mixture was concentrated under vacuum. The residual aqueous solution was washed with hexane. The combined organic extract was back extracted with saturated aqueous sodium bicarbonate. The basic aqueous extracts were combined, cooled to 0°C, and acidified with 15% aqueous potassium hydrogen sulfate to a pH of ~2. The resulting thick slurry was extracted with ethyl acetate. The combined organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to afford the title compound as white solid. Step B: Preparation of Benzyl N-tert-butoxycarbonylisonipecotate A mixture of N-tert-butoxycarbonylisonipecotic acid (12.0 g, 52.3 mmol), benzyl alcohol (6.0 mL, 58 mmol), l-(3-dimethylamino- propyl)-3-ethylcarbodiimide hydrochloride (1 1.04 g, 57.6 mmol), and 4-dimethylaminopyridine (642 mg, 5.25 mmol) in anhydrous dichloromethane (100 mL) was stirred at room temp, for 6 h. The resultant mixture was diluted with dichloromethane and washed successively with water, 10% aqueous citric acid, saturated sodium bicarbonate, and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentration under vacuum. The residual oil was subjected to column chromatography on silica eluting with 20% ethyl acetate in hexane. Collection and concentration of appropriate fractions afforded the title product as white solid. Step C: Preparation of Benzyl N-tert-butoxycarbonyl-4-(3-methyl- benzyPisonipecotate To a cold (-78 °C) solution of benzyl N-tert- butoxycarbonyl-isonipecotate (8.02 g, 25.11 mmol) in anhydrous THF (80 mL), a solution of sodium bis(trimethysilyl)amide (35 mL, 35 mmol; 1 M) in THF was added over a period of 10 min. The resulting orange solution was stirred at -78 °C for 1 h. and then treated dropwise with 3-methylbenzyl bromide (4.1 mL, 30.6 mmol). The reaction mixture was allowed to warm to room temp., and stirred overnight. The reaction was quenched with saturated aqueous ammonium chloride, diluted with water, and extracted with ethyl acetate. The organic extracts were combined, washed with brine, and concentrated under vacuum. The residual oil was subjected to column chromatography on silica eluting with 20% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title product. Step D: Preparation of N-tert-Butoxycarbonyl-4-(3-methylbenzyl)- isonipecotic acid A mixture of benzyl N-t-butoxycarbonyl-4-(3- methylbenzyP-isonipecotate (2.36 g, 5.57 mmol), 5% palladium on charcoal (250 mg), and glacial acetic acid (3 mL) in methanol (75 mL), was hydrogenated at 50 psi. in a Parr shaker at room temp, overnight. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated under vacuum to provide the title product as white solid. Step E: Preparation of N-tert-butoxycarbonyl-4-(3-methylbenzyl)- isonipecotamide A mixture of N-tert-butoxycarbonyl-4-(3-methylbenzyl)- isonipecotic acid (1.02 g, 3.00 mmol), l-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (0.64 g. 3.36 mmol), 1-hydroxy- benzotriazole hydrate (0.45 g, 3.31 mmol), ammonium chloride (0.33 g, 6.15 mmol), and diisopropylethylamine (1.15 mL, 6.60 mmol) in anhydrous dimethylformamide (10 ml) was stirred at room temp. overnight. The resultant solution was concentrated under vacuum and the residue was partitioned between ethyl acetate and water. The organic extracts were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residual oil was subjected to column chromatography on silica eluting with 40% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title product. Step F: Preparation of 4-(3-methylbenzyl)isonipecotamide hydrochloride salt To a cold (0 °C) solution of N-tert-butoxycarbonyl-4-(3- methylbenzyPisonipecotamide (700 mg) in ethyl acetate (50 mL), a stream of anhydrous hydrogen chloride gas was bubbled for 20 min. The resultant mixture was stirred at 0 °C for 1.5 h, purged with argon for 10 min., and concentrated under vacuum to provide the title compound as white solid. Step G: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyll-4-(3-methylbenzyPisonipecotamide A solution of 4-(3-methylbenzyl)isonipecotamide hydro¬ chloride salt (134 mg, 0.5 mmol), l-(4-cyanobenzyl)-5-chloromethyl- imidazole hydrochloride salt (134 mg, 0.5 mmol; Example 52, Step D), and diisopropylethylamine (440 mL, 2.5 mmol) in anhydrous acetonitrile (5 mL) was heated under reflux overnight. The resultant mixture was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 2% methanol in chloroform saturated with ammonia gas. After collection and concentration of appropriate fractions, the residue was triturated with anhydrous diethyl ether. The white solid precipitated was filtered to provide the title compound. Anal. Calcd for C26H29N5O: C, 70.67; H, 6.67; N, 15.19. Found: C, 70.72; H, 6.54; N, 15.48. EXAMPLE 82 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- methylbenzyPisonipecotamide The title compound was prepared using the protocol described in Example 81, Step A - G substituting 3-methylbenzyl bromide with 2-methylbenzyl bromide in Step C. Anal. Calcd for C26H29N5O-0.10 CH2Cl2 » 0.10 Et2θ: C, 71.77; H, 6.86; N, 15.79. Found: C, 71.64; H, 6.70; N, 15.78. EXAMPLE 83 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyI]-4-(3- methyl-benzyPisonipecotamide The title compound was prepared using the protocol described in Example 81, Step A - F, and in Example 38, Step B substituting 4-(3-methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(3-methylbenzyl)isonipecotamide hydrochloride salt. Trituration of the purified product with a mixture of dichloromethane and toluene provided the title compound as white solid. Anal. Calcd for C_ H29N5θ2*0.35 EtOAc-0.05 toluene: C, 70.32; H, 6.61; N, 14.26. Found: C, 70.24; H, 6.59; N, 14.21. EXAMPLE 84 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- methyl-benzyPisonipecotamide The title compound was prepared using the protocol described in Example 82, and in Example 38, Step B substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(2- methylbenzyP-isonipecotamide hydrochloride salt. Trituration of the purified product with a mixture of dichloromethane and toluene provided the title compound as white solid. Anal. Calcd for C27H29N5O2O.2O CH2C12-0.30 toluene: C, 70.35; H, 6.41 ; N, 14.00. Found: C, 70.26; H, 6.66; N, 13.88. EXAMPLE 85 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methyl-benzyPisonipecotamide The title compound was prepared using the protocol described in Example 81, and in Example 39, substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(3- methylbenzyP-isonipecotamide hydrochloride salt. Trituration of the purified product with a mixture of dichloromethane and toluene provided the title compound as white solid. Anal. Calcd for C26H27N5O2O.2O CH2C12-0.20 toluene: C, 69.50; H, 6.13; N, 14.68. Found: C, 69.58; H, 6.32; N, 14.62. EXAMPLE 86 Preparation of 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methyl-benzyPisonipecotamide The title compound was prepared using the protocol described in Example 82, and in Example 39, substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(2- methylbenzyl)-isonipecotamide hydrochloride salt. Trituration of the purified product with a mixture of dichloromethane and toluene provided the title compound as white solid. Anal. Calcd for C26H27N5O2-0.05 toluene: C, 70.93; H, 6.19; N, 15.70. Found: C, 70.93; H, 6.14; N, 15.73. EXAMPLE 87 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyPpiperidine-4-carbonitrile Step A: Preparation of N-tert-butoxycarbonyl-4-hydroxypiperidine To a solution of 4-hydroxypiperidine (22.9 g, 226.4 mmol), triethylamine (33 mL, 242 mmol) in dichloromethane (250 mL), a solution of di-tert-butyl dicarbonate in dichloromethane (100 mL) was added over a period of over 1 h. The resulting solution was stirred at room temp, overnight. The reaction mixture was washed with aqueous potassium hydrogen sulfate, and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to afford the title compound. Step B: Preparation of N-tert-butoxycarbonylpiperidine-4- carbonitrile To a cold (0 °C) solution of N-tert-butoxycarbonyl-4- hydroxypiperidine (1226.4 mmol) and pyridine (24.3 mL, 300 mmol) in anhydrous dichloromethane (300 mL), methanesulfonyl chloride (17.8 mL, 230 mmol) was added. The reaction mixture was stirred at room temp, overnight. The resultant mixture was diluted with dichloromethane and washed successively with 10% aqueous citric acid, saturated aqueous sodium bicarbonate, and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentration under vacuum. The residue was dissolved in a mixture of potassium cyanide (29 g, 445 mmol) and anhydrous dimethylformamide (800 mL). The reaction mxiture was heated at 100 °C overnight. The resultant slurry was filtered through a plug of Celite, and the filtrate concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 0- 10% ethyl acetate in chloroform gradient. Collection and concentration of appropriate fractions provided the title nitrile. Step C: Preparation of N-tert-butoxycarbonyl-4-(3-methyl- benzyl)piperidine-4-carbonitrile To a cold (-78 °C) solution of N-tert-butoxycarbonyl- piperidine-4-carbonitrile (4.01 g, 19.08 mmol) in anhydrous THF (60 mL), a solution of sodium bis(trimethysilyl)amide (20 mL, 20 mmol; 1 M) in THF was added over a period of 8 min. The resultant black solution was stirred at -78 °C for 1 h. and treated dropwise with 3- methylbenzyl bromide (3.08 mL, 22.8 mmol). The reaction mixture was allowed to warm to room temp., and stirred overnight. The product mixture was quenched with saturated aqueous ammonium chloride, diluted with water, and extracted with ethyl acetate. The organic extracts were combined, washed with brine, and concentrated under vacuum. The residual oil was subjected to column chromatography on silica eluting with 20% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title product. Step D: Preparation of 4-(3-methylbenzyI)piperidine-4-carbonitrile hydrochloride salt To a cold (0 °C) solution of N-tert-butoxycarbonyl-4-(3- methylbenzyl)piperidine-4-carbonitrile (1.60 g, 5.1 mmol) in ethyl acetate (100 mL), a stream of anhydrous hydrogen chloride gas was bubbled for 5 min. The resultant mixture was stirred at 0 °C for 45 minute, purged with argon for 10 min., and concentrated under vacuum to provide the title compound as white solid. Step E: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyll-4-(3-methylbenzyPpiperidine-4-carbonitrile A solution of 4-(3-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt (129 mg, 0.51 mmol), l -(4-cyanobenzyl)-5-chloro- methylimidazole hydrochloride salt (135 mg, 0.51 mmol; Example 52, Step D), and diisopropylethylamine (440 mL, 2.5 mmol) in anhydrous acetonitrile (5 mL) was heated under reflux overnight. The resultant mixture was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 85: 15 v/v mixture of chloroform saturated with ammonia gas and hexane. After collection and concentration of appropriate fractions, the residue was triturated with a mixture of ethyl acetate and diethyl ether. The white solid precipitated was filtered to provide the title compound. Anal. Calcd for C26H27N5-0.10 Et_0: C, 76.04; H, 6.77; N, 16.80. Found: C, 76.08; H, 6.80; N, 16.91. EXAMPLE 88 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile The title compound was prepared using the protocol described in Example 87, Step A - E substituting 3-methylbenzyl bromide with 2-methy lbenzy 1 bromide in Step C. Anal. Calcd for C26H27N5: C, 76.25; H, 6.65; N, 17.10. Found: C, 76.23; H, 6.79; N, 17.05. EXAMPLE 89 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(4- methylbenzyl)piperidine-4-carbonitrile The title compound was prepared using the protocol described in Example 87, Step A - E substituting 3-methylbenzyl bromide with 4-methylbenzyl bromide in Step C. Anal. Calcd for C26H27N5-0.15 CH2Cl2*0.15 H2O: C, 73.90; H, 6.55; N, 16.48. Found: C, 73.86; H, 6.22; N, 17.26. EXAMPLE 90 Preparation of l-[3-(4-Cyanobenzyl)-2-methyl-3H-imidazol-4- ylmethyl]-4-(3-methylbenzyl)piperidine-4-carbonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 87, Step A - E substituting 1 -(4-cyanobenzyl)-5- chloro-methylimidazole hydrochloride salt with l-(4-cyanobenzyl)-5- chloro-methyl-2-methylimidazole hydrochloride salt (Example 53, Step B) in Step E. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H29N5 « 2.25 TFA -1.55 H2θ: C, 53.43; H, 4.89; N, 9.89. Found: C, 53.39; H, 4.87; N, 10.04. EXAMPLE 91 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methylbenzyPpiperidine-4-carbonitrile The title compound was prepared using the protocol described in Example 87, Step A - D, and in Example 39 substituting 4- (3-methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4- (3-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt (Example 87, Step D). Anal. Calcd for C26H25N5θ-0.15Et2θ: C, 73.50; H, 6.15; N, 16.11. Found: C, 73.55; H, 6.15; N, 16.17. EXAMPLE 92 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methylbenzyPpiperidine-4-carbonitrile The title compound was prepared using the protocol described in Example 87, Step A - D, substituting 3-methylbenzyl bromide with 2-methylbenzyl bromide in Step C, and in Example 39 substituting 4-(3-methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(2-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt. Anal. Calcd for C26H25N5θ-0.10Et2θ: C, 73.58; H, 6.08; N, 16.25. Found: C, 73.67; H, 6.18; N, 16.25. EXAMPLE 93 Preparation of 1 -l3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- methylbenzyPpiperidine-4-carbonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 87, Step A - D, and in Example 38 substituting 4- (3-methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4- (3-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt (Example 87, Step D). The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H27N50-1.6 TFA-0.75 H2θ: C, 57.25; H, 4.79; N, 11.06. Found: C, 57.26; H, 4.75; N, 1 1.24. EXAMPLE 94 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile The title compound was prepared using the protocol described in Example 87, Step A - D, substituting 3-methylbenzyl bromide with 2-methylbenzyI bromide in Step C, and in Example 38 substituting 4-(3-methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with 4-(2-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt. Anal. Calcd for C27H27N5O-0.05 EtOAc-0.15 Et2θ: C, 73.69; H, 6.43; N, 15.46. Found: C, 73.71 ; H, 6.51 ; N, 15.53. EXAMPLE 95 Preparation of 1 -f 3-(4-Cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3- methylbenzyPpiperidine-4-carbonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 87, Step A - D, and in Example 78 substituting methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt with 4-(3-methyl-benzyl)piperidine-4-carbonitrile hydrochloride salt (Example 87, Step D). The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H29N5*2.6 TFA-0.04 H2θ: C, 53.66; H, 4.43; N, 9.72. Found: C, 53.66; H, 4.56; N, 9.32. EXAMPLE 96 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 87, Step A - D, substituting 3-methylbenzyl bromide with 2-methylbenzyl bromide in Step C, and in Example 78 substituting methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt with 4-(2-methylbenzyl)piperidine-4-carbonitrile hydrochloride salt. The crude product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C27H29N5 « 2.5 TFA-0.95 H2θ: C, 52.93; H, 4.52; N, 10.32. Found: C, 52.96; H, 4.64; N, 9.65. EXAMPLE 97 Preparation of 4- { 5-[4-Hydroxymethyl-4-(4-methylpyridin-2-ylmethyl)- piperidine- 1 -ylmethy l]-2-methylimidazol- 1 -ylmethyl } benzonitrile Step A: Preparation of 2-Hydroxymethyl-4-methylpyridine A mixture of 2,4-dimethylpyridine N-oxide (10.9 g, 88.5 mmol) and trifluoroacetic anhydride (31 mL, 219 mmol) in dichloromethane (75 mL) was stirred at room temp, overnight. The product mixture was concentrated under vacuum. The residue was dissolved in a mixture of dichloromethane (75 mL) and aqueous sodium carbonate (225 mL, 2M), and stirred vigorously for 4 h. The resultant mixture was diluted with dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 1-2% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided 2-hydroxymethyl-4-methylpyridine as clear oil. Step B: Preparation of 2-Chloromethyl-4-methylpyridine A mixture of 2-hydroxymethyl-4-methylpyridine (5.48 g, 44.5 mmol) and thionyl chloride (60 mL, 822 mmol) in benzene (150 mL) was stirred at room temp, overnight. The product mixture was concentrated under vacuum. The residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under vacuum to provide the title compound as oil. This alkylating reagent was passed through a small plug of activated basic alumina immediately before use. Step C: Preparation of Ethyl N-tert-butoxycarbonyl-4-(4- methylpyridin-2-ylmethyl)piperidine-4-carboxylate To a cold (-78 ° C) solution of ethyl N-tert-butoxycarbonyl- piperidine-4-carboxylate (5.1 g, 19.8 mmol; Example 30, Step A) in anhydrous THF (50 mL), a solution of solution of sodium bis(trimethyl- silyl)amide (20 mL, IM, 20 mmol) was added over a period of 15 min. The resultant mixture was stirred at -78 °C for 1 h., and 2- chloromethyl-4-methylρyridine (3.5 g, 24.7 mmol) was added. The reacting mixture was allowed to warm to room temp, and stirred overnight. The product mixture was diluted with dichloromethane was washed with brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 25- 40% ethyl acetate in hexane gradient. Collection and concentration of appropriate fractions provided the title compound. Step D: Preparation of N-tert-Butoxycarbonyl-4-(4-methylpyridin- 2-ylmethyl)-4-hydroxymethylpiperidine To a slurry of lithium aluminum hydride (280 mg, 7.37 mmol) in anhydrous diethyl ether (30 mL) at 0 °C, a solution of ethyl N-tert-butoxycarbonyl-4-(4-methylpyridin-2-ylmethyl)piperidine-4- carboxylate (2.7 g, 7.45 mmol) in diethyl ether (20 mL) was added dropwise with the temperature of the reacting mixture maintained below 10 °C. The resulting mixture was stirred at 0 °C for 30 min, and quenched with successive addition of water (0.28 mL), 15% aqueous NaOH (0.28 mL), and water (0.84 mL). The resultant slurry was stirred at room temp, for 30 min., and filtered through a small plug of Celite. The filtrate was washed brine, dried over anhydrous magnesium sulfate, and filtered. Concentration of the filtrate under vacuum provided the title alcohol. Step E: Preparation of 4-(4-methylpyridin-2-ylmethyl)-4-hydroxy- methylpiperidine hydrochloride salt A solution of N-tert-butoxycarbonyl-4-(4-methylpyridin-2- ylmethyl)-4-hydroxymethylpiperidine (1.8 g) in dichloromethane (100 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was sealed with a rubber septum and stirred at room temp, for 2.5 h. The product solution was concentrated under vacuum to provide the title compound. Step F: Preparation of 4- {5-[4-Hydroxymethyl-4-(4-methylpyridin- 2-ylmethyl)piperidine- 1 -ylmethyll-2-methylimidazol- 1 - ylmethyl } benzonitrile A mixture of 4-(4-methylpyridin-2-ylmethyl)-4-hydroxy- methylpiperidine hydrochloride salt (0.39 g, 1.3 mmol), l-(4-cyano- benzyl)-2-methylimidazole-5-carboxyaldehyde (0.33 g, 1.5 mol; Example 31, Step A), diisopropylethylamine (0.57 mL, 3.25 mmol), anhydrous magnesium sulfate (0.55 g), activated molecular sieves 3 A powder (0.55 g), and anhydrous methanol (3.5 mL) was stirred at room temp, overnight. The pH of the mixture was adjusted to ~5 with addition of glacial acetic acid. To the this mixture, a solution of sodium cyanoborohydride in THF (1.35 mL, 1 M, 1.35 mmol) was added slowly over a period of 8 h with a syringe pump, and stirred at room temp, overnight. The product mixture was diluted with chloroform, filtered through Celite. The filtrate was washed with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 5% methanol in chloroform. Collection and concentration of appropriate fractions provided a gum, which was triturated with anhydrous diethyl ether to provide the title compound as white solid. Anal. Calcd for C26H31N5O: C, 72.70; H, 7.27; N, 16.30. Found: C, 72.52; H, 7.08; N, 16.18. EXAMPLE 98 Preparation of 4-{ 5-14-Hydroxymethyl-4-(6-methylpyridin-2-ylmethyl)- piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared using the protocol described in Example 97, Step B - F substituting 2-hydroxymethyl-4- methylpyridine with 6-methyl-2-pyridinemethanol in Step B. Anal. Calcd for C26H31N5O: C, 72.70; H, 7.27; N, 16.30. Found: C, 72.96; H, 7.34; N, 16.25. EXAMPLE 99 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(2-methylpyridin-4-ylmethyl)- piperidine-l-ylmethyl1-2-methylimidazol- l-ylmethyl }benzonitrile Step A: Preparation of 2-Chloro-4-chloromethyl-6-methylpyridine To a slurry of lithium aluminum hydride (0.45 g, 1 1.9 mmol) in anhydrous diethyl ether (40 mL) at 0 °C, a solution of 2- chloro-6-methylpyridine-4-carboxylic acid (2.0 g, 1 1.7 mmol) in diethyl ether (30 mL) was added. The resulting mixture was stirred at room temp, overnight, and quenched with successive addition of water (0.45 mL), 15% aqueous NaOH (0.45 mL), and water (1.35 mL). The resultant slurry was stirred at room temp, for 30 min., and filtered through a small plug of Celite. The filtrate was washed brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide 2-chloro-4-hydroxymethyl-6-methylpyridine. The title compound was prepared using the protocol described in Example 97, Step B substituting 2-hydroxymethyl-4- methylpyridine with 2-chloro-4-hydroxymethyl-6-methylpyridine. Step B: Preparation of Ethyl N-tert-butoxycarbonyl-4-(2-chloro-6- methylpyridin-4-ylmethyl)piperidine-4-carboxylate The title compound was prepared using the protocol described in Example 97, Step C substituting 2-chloromethyl-4- methylpyridine with 2-chloro-4-chloromethyl-6-methylpyridine. Step C: Preparation of Ethyl N-tert-butoxycarbonyl-4-(2-methyl- pyridin-4-ylmethyPpiperidine-4-carboxylate A mixture of ethyl N-tert-butoxycarbonyl-4-(2-chloro-6- methylpyridin-4-ylmethyl)piperidine-4-carboxylate (0.32 g, 0.81 mmol) and 5% palladium on charcoal (60 mg) in methanol (10 mL) was stirred under a balloon of hydrogen gas at room temp, for 3 h. The resultant mixture was filtered through a plug of Celite. The filtrate was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 3 - 5% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided the title compound. Step D: Preparation of 4-{5-[4-Hydroxymethyl-4-(2-methylpyridin- 4-ylmethyl)-piperidine- 1 -vlmethyn-2-methylimidazol- 1 - ylmethyl } benzonitrile The title compound was prepared using the protocol described in Example 97, Step D - F substituting ethyl N-tert- butoxycarbonyl-4-(4-methylpyridin-2-ylmethyl)piperidine-4- carboxylate with ethyl N-tert-butoxycarbonyl-4-(2-methylpyridin-4- ylmethyl)piperidine-4-carboxylate in Step D. The final product was subjected to high pressure liquid column chromatography on C- 18 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C26H31N50-3.35 TFA: C, 48.39; H, 4.27; N, 8.63. Found: C, 48.42; H, 4.07; N, 8.49. EXAMPLE 100 Preparation of 4-{ 5-[4-Hydroxymethyl-4-(4-chloropyridin-2-ylmethyl)- piperidine-l -ylmethyll-2-methylimidazol-l -ylmethyl }benzonitrile Step A: Preparation of 2-Chloromethyl-4-chloropyridine To a slurry of lithium aluminum hydride (0.45 g, 11.9 mmol) in anhydrous diethyl ether (40 mL) at 0 °C, a solution of methyl 4-chloro-pyridine-2-carboxylate (2.0 g, 11.7 mmol) in diethyl ether (30 mL) was added. The resulting mixture was stirred at room temp, overnight, and quenched with successive addition of water (0.45 mL), 15% aqueous NaOH (0.45 mL), and water (1.35 mL). The resultant slurry was stirred at room temp, for 30 min., and filtered through a small plug of Celite. The filtrate was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide 4-chloro-2-hydroxymethylpyridine. The title compound was prepared using the protocol described in Example 97, Step B substituting 2-hydroxymethyl-4- methylpyridine with 4-chloro-2-hydroxymethylpyridine. Step B: Preparation of 4- { 5-[4-Hydroxy methyl-4-(4-chloropyridin- 2-ylmethyl)-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 - ylmethyl } benzonitrile The title compound was prepared using the protocol described in Example 97, Step C - F substituting 2-chloromethyl-4- methylpyridine with 2-chloromethyl-4-chloropyridine in Step C. Anal. Calcd for C25H28N5OCI: C, 66.73; H, 6.27; N, 15.56. Found: C, 66.52; H, 6.19; N, 15.35. EXAMPLE 101 Preparation of 4-{5-[4-Methoxymethyl-4-(6-methylpyridin-2-yJrj_eih __ piperidine- l-ylmethyl]imidazol-l-ylmethyl }benzonitrile Step A: Preparation of N-tert-Butoxycarbonyl-4-(6-methylpyridin- 2-ylmethyP-4-methoxymethylpiperidine To a suspension of potassium hydride (52 mg, dry weight, 1.3 mmol; obtained from washing 0.15 g of 35% potassium hydride dispersion in mineral oil with hexanes and drying under a stream of argon) in anhydrous THF (10 mL), N-tert-butoxycarbonyl-4-(6- methylpyridin-2-ylmethyl)-4-hydroxymethylpiperidine (0.3 g, 0.9 mmol; Example 98) in THF (2 mL) was added. The resultant mixture was stirred at room temp, for 1 h, and treated with methyl iodide (60 μL, 0.96 mmol). The reacting mixture was stirred at room temp, overnight. The product mixture was cooled to 0 °C, quenched with water, and diluted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 20-30% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of 4-{5-[4-Methoxymethyl-4-(6-methylpyridin- 2-ylmethyl)-piperidine- 1 -ylmethyllimidazol-1 -ylmethyl }- benzonitrile The title compound was prepared using the protocol described in Example 97, Step E - F substituting N-tert-butoxycarbonyl- 4-(4-methylpyridin-2-ylmethyl)-4-hydroxymethylpiperidine with N- tert-butoxycarbonyl-4-(6-methylpyridin-2-ylmethyl)-4-methoxymethyl- piperidine in Step E. The final product was subjected to high pressure liquid column chromatography on C-l 8 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C26H3 lN5θ-3.35 TFA: C, 48.39; H, 4.27; N, 8.63. Found: C, 48.42; H, 4.07; N, 8.49. EXAMPLE 102 Preparation of 4-{5-[4-Hydroxymethyl-4-(6-hydroxypyridin-2- ylmethyP-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 - ylmethyl I benzonitrile Step A: Preparation of 2-Benzyloxy-6-methylpyridine N-oxide To a cold (0 °C) solution of 2-chloro-6-methylpyridine (24.6g, 193 mmol) in dichloromethane (100 mL), a solution of m- chloro-per-benzoic acid (46.2 g, 268 mmol; purified) in dichloromethane (480 mL) was added over a period of 30 min. The reaction mixture was stirred at room temp, overnight, and concentrated to about 100 mL. The slurry was filtered, and the solid washed with ice-cold dichloromethane. The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under vacuum to provide 2-chloro-6-methylpyridine N-oxide as clear colorless oil. To a slurry of sodium hydride (4.2 g, 105 mmol; 60% dispersion in mineral oil) in anhydrous dimethyl sulfoxide (70 mL), benzyl alcohol (8.7 mL, 84 mmol) was added over a period of 10 minute. The mixture was stirred at room temp, for 10 h., and treated with a solution of 2-chloro-6-methylpyridine N-oxide (10 g, 70 mmol) in dimethyl sulfoxide (10 mL). The resultant mixture was stirred at room temp, overnight, quenched with water and aqueous hydrochloric acid (to pH 8). The mixture was extracted with chloroform. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 1-4% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided 2-benzyloxy-6-methylpyridine N-oxide as pale brown oil. Step B: Preparation of 2-Benzyloxy-6-chloromethylpyridine A mixture of 2-benzyloxy-6-methylpyridine N-oxide (3.4 g, 15.9 mmol) and acetic anhydride (125 mL) was heated under reflux for 1 h. The resulting solution was concentrated under vacuum, and the residue was partitioned between aqueous sodium bicarbonate and dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10-20% ethyl acetate in hexane gradient. Collection and concentration of appropriate fractions provided 2-acetoxymethyl-6- benzyloxypyridine as colorless oil. A mixture of 2-acetoxymethyl-6-benzyloxypyridine (1.65 g, 6.4 mmol) and aqueous sodium hydroxide (0.58 mL, 40%) in methanol (10 mL) was stirred at room temp, overnight. The resulting solution was concentrated under vacuum, and the residue was partitioned between water and dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 0-5% ethyl acetate in chloroform gradient. Collection and concentration of appropriate fractions provided 2-benzyloxy-6-hydroxymethylpyridine as colorless oil. A mixture of 2-benzyloxy-6-hydroxymethylpyridine (1.5 g, 7.0 mmol) and thionyl chloride (10 mL, 1 7 mmol) in benzene (25 mL) was stirred at room temp, overnight. The product mixture was concentrated under vacuum. The residue was partitioned between chloroform and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 5% methanol in chloroform. Collection and concentration of appropriate fractions provided 2- benzyloxy-6-chloromethylpyridine as clear, colorless oil. This alkylating reagent was passed through a small plug of activated basic alumina immediately before use. Step C: Preparation of N-tert-Butoxycarbonyl-4-(6- benzyloxypyridin-2-ylmethyP-4-hydroxymethylpiperidine The title compound was prepared using the protocol described in Example 97, Step C - D substituting 2-chloromethyl-4- methylpyridine with 2-benzyloxy-6-chloromethylpyridine in Step C. Step D: Preparation of N-tert-Butoxycarbonyl-4-(6- hydroxypyridin-2-ylmethyP-4-hydroxymethylpiperidine A mixture of N-tert-butoxycarbonyl-4-(6- benzyloxyρyridin-2-ylmethyl)-4-hydroxymethylpiρeridine (0.19 g, 0.5 mmol) and 5% palladium on charcoal (38 mg) in absolute ethanol (10 mL) was stirred under a balloon of hydrogen gas at room temp, for 3 h. The resultant mixture was filtered through a plug of Celite. The filtrate was concentrated under vacuum to provide the title compound as colorless gum. Step E: Preparation of 4-{5-[4-Hydroxymethyl-4-(6- hydroxypyridin-2-ylmethyl)piperidine- 1 -ylmethyl]-2- methylimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared using the protocol described in Example 97, Step E - F substituting N-tert-butoxycarbonyl- 4-(4-methylpyridin-2-ylmethyl)-4-hydroxymethylpiperidine with N- tert-butoxycarbonyl-4-(6-hydroxypyridin-2-ylmethyl)-4- hydroxymethyl-piperidine in Step E. Anal. Calcd for C25H29N5θ2 « 1.25 H2O-0.40 Et2θ: C, 66.04; H, 7.40; N, 14.48. Found: C, 66.06; H, 7.02; N, 14.18. EXAMPLE 102 A Preparation of 4-[5-(4-Hydroxymethyl-4-quinolin-2-ylmethyl- piperidine- 1 -ylmethyl)-2-methylimidazol- 1 - ylmethyllbenzonitrile The title compound was prepared using the protocol described in Example 97, Step C - F substituting 2-hydroxymethyl-4- methylpyridine with 2-chloromethylquinoline in Step C. The alkylating reagent, 2-chloromethylquinoline, was generated from 2- chloromethylquinoline hydrochloride salt immediately before use. Anal. Calcd for C29H31N5O: C, 74.81 ; H, 6.71 ; N, 15.04. Found: C, 74.45; H, 6.67; N, 15.07. EXAMPLE 103 Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (3-methylbenzoyl)piperidine-4-carboxylate Step A: Preparation of Methyl N-tert-butoxycarbonyl-4-(3- methylbenzoyPpiperidine-4-carboxylate To a cold (-78 °C) solution of methyl N-tert- butoxycarbonyl-piperidine-4-carboxylate (0.25 g, 1.03 mmol; Example 3, Step B) in anhydrous THF (10 mL), a solution of sodium bis(trimethylsilyl)amide (1.2 mL, IM, 1.2 mmol) was added over a period of 5 min. The resultant mixture was stirred at -78 °C for 1 h., and 3-methylbenzoyl chloride (135 μL, 1.02 mmol) was added. The reacting mixture was allowed to warm up to room temp, and stirred overnight. The product mixture was diluted with ethyl acetate and washed with brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 8- 10% ethyl acetate in hexane gradient. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of Methyl 4-(3-methylbenzoyl)piperidine-4- carboxylate hydrochloride salt A solution of methyl N-tert-butoxycarbonyl-4-(3-methyl- benzoy l)piperidine-4-carboxylate (77 mg) in ethyl acetate ( 10 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was stirred at 0 °C for 2.5 h. The product solution was concentrated under vacuum to provide the title compound. Step C. Preparation of Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4__ ylmethyl]-4-(3-methylbenzoyPpiperidine-4-carboxylate A solution of methyl 4-(3-methylbenzoyl)piperidine-4- carboxylate hydrochloride salt (58 mg, 0.2 mmol), l -(4-cyanobenzyl)- 5-chloromethylimidazole hydrochloride salt (52 mg, 0.19 mmol), and diisopropylethylamine (174 μL, 1 mmol) in anhydrous acetonitrile (4 mL) was heated at 60 °C overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 2.5% methanol in ethyl acetate. Collection and concentration of appropriate fractions provided the title compound. Anal. Calcd for C27H28N4O3O.25 H2O: C, 70.34; H, 6.23; N, 12.15. Found: C, 70.27; H, 6.18; N, 12.27. EXAMPLE 104 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzoyPpiperidine Step A: Preparation of l-tert-Butoxycarbonyl-4-(3-methyl- benzoy 1 )piperidine A mixture of 1-tert-butoxycarbonylisonipecotic acid (5 g, 21.8 mmol; Example 81, Step A), N,0-dimethylhydroxylamine hydrochloride (2.12 g, 21.7 mmol), N-ethyl-N * -(3- dimethylaminopropyl)carbodiimide-hydrochloride (4.6 g, 24 mmol), 1 - hydroxy-7-azabenzotriazole (0.3 g, 2.2 mmol), and anhydrous dimethylformamide (50 mL) was stirred at room temp, overnight. The resulting mixture was concentrated under vacuum, and the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide N-Methoxy-N-methyl 1-tert-butoxycarbonylisonipecotamide. To a cold (-78 °C) solution of N-Methoxy-N-methyl 1-tert- butoxycarbonylisonipecotamide (1.54 g, 5.65 mmol) in anhydrous THF (25 mL), a solution of 3-methylphenylmagnesium bromide (25 mL, 1 M) in THF was added. The reacting mixture was allowed to warm up to room temp, and stirred overnight. The product mixture was quenched with 10% aqueous citric acid and diluted with diethyl ether. The organic extract was washed with aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10-15% ethyl acetate in hexane gradient. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylbenzoyl)piperidine The title compound was prepared as white solid according to the procedure described in Example 103, Step B - C substituting methyl N-tert-butoxycarbonyl-4-(3-methylbenzoyl)piperidine-4- carboxylate with N-tert-butoxycarbonyl-4-(3-methylbenzoyl)piperidine in Step B. Anal. Calcd for C25H26N40: C, 75.35; H, 6.58; N, 14.06. Found: C, 75.38; H, 6.80; N, 14.12. EXAMPLE 105 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (hydroxy-m-tolylmethvPpiperidine A solution of l-[3-(4-cyanobenzyI)-3H-imidazol-4- ylmethyl]-4-(3-methylbenzoyl)piperidine (175 mg, 0.44 mmol; Example 104) in methanol (5 mL) was treated with sodium borohydride (12 mg, 0.31 mmol) at room temp. The resultant solution was stirred at room temp, for 30 min., and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with chloroform saturated with ammonia gas. Collection and concentration of appropriate fractions provided the title product. Anal. Calcd for C25H28N4O-0.25 Et2θ-0.55 H2θ: C, 72.80; H, 7.43; N, 13.06. Found: C, 72.74; H, 7.06; N, 13.05. EXAMPLE 106 Preparation of 4-{5-[4-Hydroxymethyl-4-(3-tolylsulfanyl)piperidine-l- ylmethyl] imidazol- 1 -ylmethyl } benzonitrile trifluoroacetate salt Step A: Preparation of Ethyl N-tert-butoxycarbonyl-4-(3- tolylsulfanyPpiperidine-4-carboxylate To a cold (-78 °C) solution of ethyl N-tert-butoxycarbonyl- piperidine-4-carboxylate (2.6 g, 10 mmol; Example 30, Step A) in anhydrous THF (40 mL), a solution of sodium bis(trimethylsilyl)amide (12 mL, IM, 12 mmol) was added over a period of 10 min. The resultant mixture was stirred at -78 °C for 1 h., and di-3-methylphenyl disulfide (2.96 g, 12 mmol) was added. The reacting mixture was allowed to warm up to room temp, and stirred overnight. The product mixture was diluted with ethyl acetate and washed with brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 10-15% ethyl acetate in hexane gradient. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of N-tert-Butoxycarbonyl-4-hydroxymethyl-4- (3-tolylsulfanyPpiperidine To a slurry of lithium aluminum hydride (0.25 g, 6.6 mmol) in anhydrous diethyl ether (60 mL) at 0 °C, a solution of ethyl N-tert-butoxycarbonyl-4-(3-tolylsulfanyl)piperidine-4-carboxylate (2.25 g, 5.9 mmol) in diethyl ether (5 mL) was added dropwise with the temperature of the reacting mixture maintained below 10 °C. The resulting mixture was stirred at 0 °C for 1 h., and quenched with successive addition of water (0.25 mL), 15% aqueous NaOH (0.25 mL), and water (10.75 mL). The resultant slurry was stirred at room temp, for one h., and filtered through a small plug of Celite. The filtrate was washed brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title alcohol. Step C: Preparation of 4-hydroxymethyl-4-(3- tolylsulfanyPpiperidine hydrochloride salt A solution of N-tert-butoxycarbonyl-4-hydroxymethyl-4- (3-tolylsulfanyl)piperidine (0.27 g) in dichloromethane (25 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was sealed with a rubber septum and stirred at 0 °C for one h. The product solution was concentrated under vacuum to provide the title compound. Step D: Preparation of 4-{ 5-[4-Hydroxymethyl-4-(3-tolylsulfanyl)- piperidine- 1 -ylmethyl] imidazol- 1 -ylmethyl } benzonitrile trifluoroacetate salt A mixture of 4-hydroxymethyl-4-(3- tolylsulfanyPpiperidine hydrochloride salt (0.23 g, 0.85 mmol), l-(4- cyanobenzyl)imidazole-5-carboxyaldehyde (0.20 g, 0.95 mmol; Example 1, Step E), diisopropyl-ethylamine (0.22 mL, 1.3 mmol), anhydrous magnesium sulfate (500 mg), activated powdered molecular sieves 3 A (500 mg), and anhydrous methanol (3 mL) was stirred at room temp, overnight. The pH of the mixture was adjusted to ~5 with addition of glacial acetic acid. To the this mixture, a solution of sodium cyanoborohydride in THF (0.9 mL, 1 M, 0.9 mmol) was added slowly over a period of 3 h. with a syringe pump, and stirred at room temp. overnight. The product mixture was diluted with chloroform, filtered through Celite. The filtrate was washed with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 3-5% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided the free base. The product was purified with high pressure liquid column chromatography on C- 18 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid. Anal. Calcd for C25H28N40S-2.7 TFA-0.45 H2θ: C, 48.78; H, 4.26; N, 7.48. Found: C, 48.80; H, 4.28; N, 7.37. EXAMPLE 107 Preparation of 4-{5-14-Methoxymethyl-4-(3-tolylsulfanyl)piperidine- l- ylmethyllimidazol-1 -ylmethyl } benzonitrile trifluoroacetate salt Step A: Preparation of N-tert-Butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfanyl)piperidine To a suspension of potassium hydride (0.18 g, dry weight, 4.5 mmol; obtained from washing 0.52 g of 35% potassium hydride dispersion in mineral oil with hexanes and drying under a stream of argon) in anhydrous THF (25 mL), N-tert-butoxycarbonyl-4-(3- tolylsulfanyl)-4-hydroxymethylpiperidine (0.96 g, 2.8 mmol; Example 106, Step B) in THF (5 mL) was added. The resultant mixture was stirred at room temp, for 1 h., and treated with methyl iodide (0.31 mL, 4.97 mmol). The reacting mixture was stirred at room temp, overnight. The product mixture was cooled to 0 °C, quenched with water, and diluted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title compound. Step B: Preparation of 4-Methoxymethyl-4-(3- tolylsulfanyPpiperidine hydrochloride salt A solution of N-tert-butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfanyl)ρiperidine (0.18 g) in ethyl acetate (25 mL) at 0 °C was saturated with hydrogen chloride gas. The resultant solution was stirred at 0 °C for one h. The product solution was concentrated under vacuum to provide the title compound. Step C: Preparation of 4-{5-[4-Methoxymethyl-4-(3-tolylsulfanyl)- piperidine- 1 -ylmethyl] imidazol- 1 -ylmethyl Jbenzonitrile trifluoroacetate salt The title compound was prepared using the protocol described in Example 106, Step D substituting 4-hydroxymethyl-4-(3- tolylsulfanyl)-piperidine hydrochloride salt with 4-methoxymethyl-4-(3- tolylsulfanyl)-piperidine hydrochloride salt. Anal. Calcd for C26H30N4OS-2.45 TFA-1.1 H2θ: C, 49.77; H, 4.68; N, 7.51. Found: C, 49.77; H, 4.68; N, 7.39. EXAMPLE 108 Preparation of 4-{ 5-[4-Methoxymethyl-4-(3-tolylsulfinyl)piperidine- l- ylmethyl limidazol- 1 -ylmethyl }benzonitrile Step A: Preparation of N-tert-Butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfinyl)piperidine A mixture of N-tert-butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfanyl)piperidine (0.30 g, 0.85 mmol; Example 107, Step A) and sodium periodate (0.2 g, 0.94 mmol) in a mixture of methanol (6 mL) and water (4 mL) was stirred at room temp, overnight. The reaction mixture was diluted with dichloromethane. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 35% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of 4- { 5-[4-Methoxymethyl-4-(3-tolylsulfinyl)- piperidine- 1 -ylmethyllimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared using the protocol described in Example 107, Step B substituting N-tert-butoxycarbonyl-4- methoxy-methyl-4-(3-tolylsulfanyl)piperidine with N-tert- butoxycarbonyl-4-methoxymethyl-4-(3-tolylsulfinyl)piperidine, and in Example 103, Step C substituting 4-(3-methylbenzoyl)piperidine-4- carboxylate hydrochloride salt with 4-methoxymethyl-4-(3- tolylsulfinyPpiperidine hydrochloride salt. Anal. Calcd for C26H30N4O2S-0.8 H2θ: C, 65.47; H, 6.68; N, 1 1.75. Found: C, 65.53; H, 6.35; N, 11.66. EXAMPLE 109 Preparation of 4- { 5-[4-Methoxymethyl-4-(3-tolylsulfonyl)piperidine- 1 ylmethyllimidazol- 1 -ylmethyl Ibenzonitrile Step A: Preparation of N-tert-Butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfinyl)piperidine A solution of N-tert-Butoxycarbonyl-4-methoxymethyl-4- (3-tolylsulfanyl)piperidine (0.26 g, 0.73 mmol; Example 107, Step A) in acetonitrile (10 mL) was treated with a solution of Oxone (0.99 g, 1.6 mmol) in water (10 mL) and potassium bicarbonate (0.56 g, 5.6 mmol) in water (10 mL), and stirred at room temp, for 1 h. The reaction mixture was diluted with dichloromethane and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 25% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound. Step B: Preparation of 4- { 5-[4-Methoxymethyl-4-(3-tolylsulfonyl)- piperidine- 1 -ylmethyllimidazol- 1 -ylmethyl }benzonitrile The title compound was prepared using the protocol described in Example 107, Step B substituting N-tert-butoxycarbonyl-4- methoxy-methyl-4-(3-tolylsulfanyl)piperidine with N-tert- butoxycarbonyl-4-methoxymethyl-4-(3-tolylsulfonyl)piperidine, and in Example 103, Step C substituting 4-(3-methylbenzoyl)piperidine-4- carboxylate hydrochloride salt with 4-methoxymethyl-4-(3- tolylsulfonyPpiperidine hydrochloride salt. Anal. Calcd for C26H30N4O3S-0.6 H2θ: C, 63.81; H, 6.43; N, 1 1.45. Found: C, 63.86; H, 6.11 ; N, 11.32. EXAMPLE 110 Preparation of 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)isonipecotamide Step A: Preparation of l-Benzyl-4-cyano-4-(3- methylphenylamino)-piperidine To a solution of l-benzyl-4-piperidone (18.9 g, 0.1 mol) and 3-methylaniline (10.7 g, 0.1 mol) in glacial acetic acid (100 mL), trimethylsilyl cyanide (6.7 mL, 0.1 mol; Journal of Organic Chemistry, vol.55, page 4207, year 1990) was added dropwise with the temp, of the reaction maintained <40 °C with a ice-water bath. After the addition was complete, the reaction mixture was stirred at room temp, for 30 min, and poured into a mixture of ice (140 g) and concentrated ammonium hydroxide (168 g). The resultant mixture was extracted with chloroform (3 times). The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residual oil was triturated with diisopropyl ether (300 mL) and stirred at room temp, overnight. The white solid precipitated was filtered to provide the title compound. Step B: Preparation of l-Benzyl-4-(3-methylphenylamino)- isonipecotamide A mixture of l-benzyl-4-cyano-4-(3-methylphenylamino)- piperidine (7.6 g) and 90% sulfuric acid (53 mL) was heated 70 °C until all the solid dissolved (~ 1 h). The resultant mixture was stirred at the temp, for 30 min., and poured into a mixture of ice (80 g) and concentrated ammonium hydroxide (75 g). The solution was basified with ammonium hydroxide, and extracted with chloroform. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the title compound. Step C: Preparation of 4-(3-methylphenylamino)isonipecotamide hydrochloride salt A mixture of l-benzyl-4-(3-methylphenylamino)- isonipecotamide (0.42 g, 1.3 mmol) and 10% palladium on charcoal (0.88 g) in a mixture of ethanol (40 mL) and ethanol saturated with anhydrous hydrochloride gas ( 10 mL) was shaken in a Parr hydrogenator at 60 psi for 48 h. The resultant mixture was filtered through a plug of Celite, and the filtrate concentrated to provide the title compound. Step D: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylphenylamino)isonipecotamide The title compound was prepared using the protocol described in Example 106, Step D substituting 4-hydroxymethyl-4-(3- tolylsulfanyl)-piperidine hydrochloride salt with 4-(3- methylphenylamino)-isonipecotamide hydrochloride salt. Anal. Calcd for C25H28N6O-0.15 Et2θ-0.65 H2θ: C, 68.12; H, 6.88; N, 18.62. Found: C, 68.14; H, 6.73; N, 18.65. EXAMPLE 1 1 1 Preparation of Ethyl l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- (3-methylphenylamino)piperidine-4-carboxylate Step A: Preparation of Ethyl l -Benzyl-4-(3-methylphenylamino)- piperidine-4-carboxylate A solution of l-benzyl-4-(3-methylphenylamino)- isonipecotamide (4.5 g, 13.9 mmol) and potassium hydroxide (3.g, 53.5 mmol) in ethylene glycol (35 mL) was heated under reflux. The resulting mixture was diluted with water and neutralized with acetic acid. The white solid precipitated was filtered, washed with chloroform to provide 1 -benzyl-4-(3-methylphenylamino)piperidine-4-carboxylic acid. A mixture of l-benzyl-4-(3-methylphenylamino)piperidine- 4-carboxylic acid (3.81 g, 11.7 mmol) and concentrated sulfuric acid (2 mL) in absolute ethanol (80 mL) was heated under reflux overnight. The resultant solution was concentrated under vacuum, and the residue was treated with chloroform saturated with ammonia gas. The mixture was filtered, and the filtrate concentrated. The residue was passed through a small plug of silica gel eluting with chloroform saturated with ammonia gas. Collection and concentration of the eluent under vacuum provided the title compound. Step B: Preparation of Ethyl l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylphenylamino)piperidine-4- carboxylate The title compound was prepared using the protocol described in Example 110, Step C - D substituting l-benzyl-4-(3- methylphenyl-amino)isonipecotamide with ethyl l-benzyl-4-(3- methylphenylamino)-piperidine-4-carboxylate. Anal. Calcd for C27H31N5O2O.3 Et2θ: C, 70.59; H, 7.14; N, 14.60. Found: C, 70.57; H, 7.07; N, 14.56. EXAMPLE 112 Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- hydroxymethyl-4-(3-methylphenylamino)piperidine Step A: Preparation of l-Benzyl-4-hydroxymethyl-4-(3- methylphenylamino)piperidine To a slurry of lithium aluminum hydride (330 mg, 8.7 mmol) in anhydrous diethyl ether (25 mL) at 0 °C, a solution of ethyl 1- benzyl-4-(3-methylphenylamino)piperidine-4-carboxylate (2.8 g, 7.94 mmol) in diethyl ether (10 mL) was added dropwise with the temp, of the reacting mixture maintained below 10 °C. The resulting mixture was stirred at 0 ° C for 30 min, and quenched with successive addition of water (0.33 mL), 15% aqueous NaOH (0.33 mL), and water ( 1 mL). The resultant slurry was stirred at room temp, for 30 min., and was filtered through a small plug of Celite. The filtrate was washed brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the title alcohol as white solid. Step B: Preparation of 4-hydroxymethyl-4-(3-methylphenylamino)- piperidine hydrochloride salt A mixture of l-benzyl-4-hydroxymethyl-4-(3- methylphenylamino)piperidine (0.2 g, 0.64 mmol) and 10% palladium on charcoal (0.4 g) in a mixture of methanol (15 mL) and methanol saturated with anhydrous hydrochloride gas (10 mL) was shaken in a Parr hydrogenator at 60 psi for 24 h. The resultant mixture was filtered through a plug of Celite, and the filtrate was concentrated to provide the title compound. Step C: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-hydroxymethyl-4-(3-methylphenyl- amino)piperidine The title compound was prepared using the protocol described in Example 110, Step D substituting 4-(3- methylphenylamino)-isonipecotamide hydrochloride salt with 4- hydroxymethyl-4-(3-methylphenylamino)piperidine hydrochloride salt. Anal. Calcd for C25H29N5O-0.1 H2θ: C, 71.94; H, 7.05; N, 16.78. Found: C, 71.76; H, 7.09; N, 17.17. EXAMPLE 1 12A Preparation of 0-{ l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylpheny lamino)piperidyl-4-methyl } carbamate Step A: Preparation of 0-[l-Benzyl-4-(3- methylρhenylamino;piperidyl-4-methyl]carbamate A mixture of l-benzyl-4-hydroxymethyl-4-(3- methylphenyl-amino)piperidine (0.25 g, 0.81 mmol; Example 1 12, Step A), l,l '-carbonyldiimidazole (0.14 g, 0.89 mmol) and dichloromethane (2 mL) was stirred at room temp, overnight. The resultant solution was concentrated, and the residue subjected to column chromatography on silica gel eluting with 5% methanol in chloroform. Collection and concentration of appropriate fraction provided l-[l-benzyl-4-(3- methylphenylamino)-piperidylmethyloxy]carbonyl- 1 '-imidazole. This material was dissolved in chloroform saturated with ammonia gas. The reaction mixture was sealed with a rubber septum, and stirred at room temp, for 2 days. The resultant mixture was concentrated, and the residue subjected to column chromatography on silica gel eluting with 8% methanol in chloroform. Collection and concentration of appropriate fraction provided the title compound. Step B: Preparation of 0-{ l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylphenylamino)piperidyl-4- methy 1 } carbamate The title compound was prepared using the protocol described in Example 110, Step C - D substituting 1 -benzyl-4-(3- methylphenyl-amino)isonipecotamide with 0-[l-Benzyl-4-(3- methylphenylamino)-piperidyl-4-methyl]carbamate. Anal. Calcd for C26H3θN6θ2 β 0.2 H2θ: C, 67.56; H, 6.63; N, 18.18. Found: C, 67.60; H, 6.28; N, 18.13. EXAMPLE 1 12B Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylurea Step A: Preparation of l-Benzyl-4-(3-methylphenylamino)-4- aminomethylpiperidine A mixture of l-benzyl-4-cyano-4-(3-methylphenylamino)- piperidine (4.0 g; Example UO, Step A) and 5% rhodium on alumina (4 g) in absolute ethanol (100 mL) treated with anhydrous ammonia gas (8 g) was hydrogenated at 55 psi at room temp, for 24 h. The resultant mixture was filtered through a plug of Celite, and the filtrate concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 1 : 1 mixture of 5% methanol in chloroform and chloroform saturated with ammonia gas. Collection and concentration of appropriate fractions provided the title triamine as clear, colorless, viscous oil. FAB MS m/e 310 (M+l) Step B: Preparation of [l-Benzyl-4-(3- mfithy1ρhenylamino)piperidin-4-ylmethyHurea A mixture of l -benzyl-4-(3-methylphenylamino)-4- aminomethylpiperidine (247 mg, 0.79 mmol) and nitrourea (253 mg, 2.4 mmol) in mixture of acetonitrile (1 mL) and water (10 drops) was stirred at room temp, for 48 hrs. The resultant mixture was concentrated under vacuum, and the residue was subjected to column chromatography on silica gel eluting with a 1 : 1 mixture of 15% methanol in chloroform and chloroform saturated with ammonia gas. Collection and concentration of appropriate fractions provided the title compound. Step C: Preparation of H3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylphenylamino)piperidyl-4-methylurea The title compound was prepared using the protocol described in Example 110, Step C - D substituting 1 -benzyl-4-(3- methylphenylamino)isonipecotamide with [l-benzyl-4-(3- methyIphenylamino)piperidin-4-ylmethyl]urea. EXAMPLE 1 12C Preparation of l-[3-(4-CyanobenzyI)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylsulfamide Step A: Preparation of [l-Benzyl-4-(3- methylphenylamino)piperidin-4-ylmethynsulfamide To a cold (5 °C) solution of chlorosulfonyl isocyanate in THF, anhydrous formic acid is added (Journal of Organic Chemistry, vol 54, page 5825, (1989)). The resultant mixture is stirred until gas evolution ceased, and treated with a solution of l-benzyl-4-(3- methylphenylamino)-4-aminomethylpiperidine in THF. The mixture is stirred at room temp, overnight to provide the title compound. Step B: Preparation of l-[3-(4-Cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylphenylamino)piperidyl-4- methylsulfamide The title compound is prepared using the protocol described in Example 110, Step C - D substituting l -benzyl-4-(3- methylphenylamino)-isonipecotamide with [l-benzyl-4-(3- methylphenylamino)piperidin-4-ylmethyl]sulfamide. EXAMPLE 113 Preparation of 4-{ 5-[4-(Hydroxydiphenylmethyl)piperidin-l ylmethyllimidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 103, Step C substituting methyl 4-(3-methylbenzoyl)piperidine-4-carboxylate hydrochloride salt with α, -diphenyl-4-piperidinemethanol in Step B. Anal. Calcd for C30H30N4O: C, 77.59; H, 6.70; N, 11.83. Found: C, 77.39; H, 6.69; N, 12.00. EXAMPLE 1 14 Preparation of 4-{5-[4-(Hydroxydiphenylmethyl)piperidine-l carbony 11 imidazol- 1 -ylmethyl } benzonitrile The title compound was prepared as white solid according to the procedure described in Example 39 substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with α,α- diphenyl-4-piperidinemethanol in Step B. Anal. Calcd for C30H28N4O-0.8 H2O-0.35 Et2θ: C, 72.96; H, 6.45; N, 10.84. Found: C, 73.00; H, 6.36; N, 10.83. EXAMPLE 1 15 Preparation of 4-(5-{2-[4-(Hydroxydiphenylmethyl)piperidin-l-yl]-2- oxoethyl}-3H-imidazol-1-ylmethyl)benzonitrile The title compound was prepared as white solid according to the procedure described in Example 38, Step B substituting 4-(3- methylbenzyl)-4-hydroxymethylpiperidine hydrochloride salt with ,α- diphenyl-4-piperidinemethanol in Step B. Anal. Calcd for C31H30N4O2: C, 75.89; H, 6.16; N, 1 1.42. Found: C, 75.60; H, 6.20; N, 1 1.25. EXAMPLE 116 l-(Piperidin-4-ylmethyP-5-(4-cyanobenzyl)imidazole bis hydrochloride Step A: l -Trityl-4-(4-cyanobenzyP-imidazole To a suspension of activated zinc dust (3.57g, 54.98 mmol) in THF (50 mL) was added dibromoethane (0.315 mL, 3.60 mmol) and the reaction stirred under argon for 45 minutes, at 20°C. The suspension was cooled to 0°C and α-bromo-p-tolunitrile (9.33g, 47.6 mmol) in THF (100 mL) was added dropwise over a period of 10 minutes. The reaction was then allowed to stir at 20°C for 6 hours and bis(triphenylphosphine) Nickel II chloride (2.40g, 3.64 mmol) and 4- iodo-1-trity limidazole (15.95g, 36.6 mmol, S. V. Ley, et al., J. Org. Chem. 56, 5739 (1991)) were added in one portion. The resulting mixture was stirred 16 hours at 20°C and then quenched by addition of saturated NH 4 C1 solution (100 mL) and the mixture stirred for 2 hours. Saturated aq. NaHCOs solution was added to give a pH of 8 and the solution was extracted with EtOAc (2 x 250 mL), dried (MgSO- and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 0-20% EtOAc in CH2CI2) to afford the title compound as a white solid. iH NMR (CDCI3, 400Mz) δ (7.54 (2H, d, J=7.9Hz), 7.38(1H, s), 7.36- 7.29 (11H, m), 7.15-7.09(6H, m), 6.58(1 H, s) and 3.93(2H, s) ppm. Step B: N-t-butoxycarbonyl-4-hydroxymethyl piperidine. To a solution of N-t-butoxycarbonyl isonipecotic acid (15.0 g, 65.4 mmol) from example 3 step A, in anhydrous THF (50ml), was added borane (65.4 ml of a IM solution in THF, 65.4 mmol) at room temperature. After 72 hours methanol (50ml) was added and the solvent evaporated in vacuo. The residue was dissolved in methanol (100ml) and the solvent evaporated in vacuo. The eesidue was partitioned between EtOAc and NaHC0 3 , the organic layer separated and washed with brine, dried (MgS0 4 ) and evaporated in vacuo. The residue was purified by chromatography (Silica gel, eluting with 50% EtOAc in hexanes ) to afford the title compound. Step C: l-(N-t- Butoxycarbonyl-piperidin-4-ylmethyl)-5-(4- cyanobenzyPimidazole To l-trityl-4-(4-Cyanobenzyl)-imidazoIe (1.99g, 4.64 mmol) in CH2CI2 (9.3 mL), Hunigs base (1.62mL, 9.28mmol) and the product from step B (l .Og 4.64mmol) at -78°C was added trifluoromethanesulfonic anhydride (0.78mL, 4.64 mmol). After 45minutes the reaction was allowed to warm to room temperature. The solvent was evaporated and the residue was dissolved in methanol (50 ml) and heated at reflux for 1 hour, cooled and evaporated to dryness. The residue was partitioned between sat. aq. NaHC03 solution and CH2CI2. The organic layer was dried, (MgSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 3% MeOH in CH2CI2) to afford the title compound. IH NMR CD3OD δ 7.69(2H, d, J=8.05Hz), 7.61(lH,s), 7.41 (2H,d, J=8.05Hz), 6.75(lH,s), 4.10(2H,s), 4.03(2H,brd, J=13.4Hz), 3.73(2H,d, J=7.3Hz),3.50-3.30(2H,m), 2.60(2H,m), 1.80-1.55(2H,m), 1.43(9H,s) and 1.10- 1.00 (2H,m) ppm. Step D: l-(Piperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole bis hydrochloride Into a solution of the product from step C (0.843g, 2.21 mmol) in EtOAc (200 mL) at 0°C was bubbled HCl gas. After 10 minutes the solvent was evaporated in vacuo to afford the title compound as a foam. Anal. Calcd for Cl7H20N4 « 2.15 HC1-0.55 H 2 0 C, 55.38; H, 6.36; N, 15.2. Found: C, 55.39; H, 6.36; N, 14.82. EXAMPLE 1 17 1 -( 1 -Pheny lρiperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt The amine from Example 1 16, step D (0.16g, 0.566 mmol) and triethylamine (0.158mL 1.32 mmol) in CH2CI2 (2.5 mL) at room temperature was added triphenyl bismuth (0.409g, 8.49 mmol) and Copper (II) acetate (0.154g, 0.849 mmol) and the reaction was stirred for 12 hours. The reaction was quenched by the addition of sat NH40H and CH2CI2 . The mixture was filtered and the filtrate extracted with CH2CI2 dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica Gel, eluting with 3% MeOH in CH2CI2). The product was converted to the hydrochloride salt. IH NMR CD3OD δ 9.11(lH,s), 7.78(2H,d, J=8.2Hz), 7.71(2H,d, J=7.9Hz), 7.70-7.50(5H,m), 7.28(lH,s), 4.33(2H,s), 4.21(2H,d, J=7.5Hz), 3.80-3.50(4H,m), 2.38(lH,m) and 2.05- 1.85(4H,m) ppm. Anal. Calcd for C23H24N4-2.15 HC1-1.40 H 2 0 C, 60.05; H, 6.34; N, 12.18. Found: C, 60.07; H, 6.34; N, 12.35. FAB HRMS exact mass calcd for C23H25N4: 357.2073724(MH+); found 3572079910. EXAMPLE 118 1 -( 1 -(2-methylphenyl)piperidin-4-y lmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt The amine from Example 1 16, step D (0.16g, 0.566 mmol) and triethylamine (0.158mL 1.32 mmol) in CH2CI2 (2.5 mL) at room temperature was added tris-2-methylphenyl bismuth (0.440g, 8.49 mmol) and Copper (II) acetate (0.154g, 0.849 mmol) and the reaction was stirred for 12 hours. The reaction was quenched by the addition of sat NH 4 OH and CH2CI2 . The mixture was filtered and the filtrate extracted with CH2CI2 dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica Gel, eluting with 3% MeOH in CH2CI2). The product was converted to the hydrochloride salt. IH NMR CD3OD δ 9.1 1(lH,s), 7.78(2H,d, J=7.8Hz), 7.60 (lH,m), 7.55(2H,d, J=7.9Hz), 7.50-7.35(3H,m), 7.29(lH,s), 4.33(2H,s), 4.21(2H,d, J=7.1Hz), 3.80-3.40(4H,m), 2.57(3H,s), 2.31 (lH,m) and 2.05- 1.85(4H,m) ppm. Anal. Calcd for C24H26N4 « 2.45 HC1-1.55 H 2 0 C, 59.10; H, 6.52; N, 11.49. Found: C, 59.16; H, 6.51; N, 11.26. EX AMPLE 119 1 -( 1 -(2-chlorobenzoy l)piperidin-4-ylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt The amine hydrochloride from Example 116, step D (0.06 lg, 0.194 mmol) and triethylamine (0.108mL 0.775 mmol) in CH2CI2 (2.0 mL) at 0°C was added 2 chlorobenzoyl chloride (0.025mL, 0.203 mmol) and the reaction was allowed to warm to room temperature and stirred for 12 hours. The reaction was quenched by the addition of sat Na2C03 and extracted into EtOAcThe organic extracts were washed with brine, dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, eluting with 3% MeOH in CH2CI2). The product was converted to the hydrochloride salt. FAB MS 419 (MH+) Anal. Calcd for C24H22N40C1- 1.35 HC1-0.35 CH 3 CN C, 61.58; H, 5.13; N, 12.84. Found: C, 61.48; H, 5.47; N, 12.84. EXAMPLE 120 l-(l-(3-chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt The amine hydrochloride from Example 1 16, step D (0.059g, 0.189 mmol) and triethylamine (0.105mL 0.775 mmol) in CH2CI2 (2.0 mL) at 0°C was added 3-chlorobenzoyl chloride (0.025mL, 0.198 mmol) and the reaction was allowed to warm to room temperature and stirred for 12 hours. The reaction was quenched by the addition of sat Na 2 C0 3 and extracted into EtOAcThe organic extracts were washed with brine, dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, eluting with 3% MeOH in CH2CI2). The product was converted to the hydrochloride salt. FAB MS 419 (MH+) Anal. Calcd for C24H22N40C1-1.35 HC1-0.25 CH 3 CN C, 61.63; H, 5.09; N, 12.47. Found: C, 61.68; H, 5.42; N, 12.44. EXAMPLE 121 1 -( 1 -(3-chlorobenzenesulfonyl)piperidin-4-y lmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt The amine hydrochloride from Example 1 16, step D (0.066g, 0.187 mmol) and triethylamine (0.84mL 0.60 mmol) in CH2CI2 (2.0 mL) at 0°C was added 3-chlorobenzenesulfonyl chloride (0.043g, 0.21 mmol) and the reaction was allowed to warm to room temperature and stirred for 1 hour. The reaction was quenched by the addition of sat Na 2 C0 3 and extracted into EtOAcThe organic extracts were washed with brine, dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, eluting with 3% MeOH in CH2CI2). The product was converted to the hydrochloride salt. Anal. Calcd for C23H 2 3N 4 O 2 ClS-1.00 HC1-0.35 H 2 0 C, 55.50; H, 5.00; N, 1 1.26. Found: C, 55.51 ; H, 4.99; N, 11.31. IH NMR CD3OD δ 8.91(lH,s), 7.75-7.55(6H,m), 7.44(2H,d, J=8.6Hz), 7.27(lH,s), 4.21(2H,s), 4.02(2H,d, J=7.1 Hz), 3.79 (2H,d, J=11.9Hz), 2.16(2H,dd, J-12.1 and 10.2Hz), 1.70-1.50(3H,m), and 1.40- 1.20(2H,m) ppm. EXAMPLE 122 l-(l-(3-chlorobenzyl)piperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt To the amine hydrochloride from Example 1 16, step D (0.092g, 0.261 mmol) and 3A molecular sieves (0.30g) in MeOH (5.0 mL) at room temperature was added 3-chlorobenzaldehyde (0.043g, 0.21 mmol) and the reaction was stirred for 30 minutes, sodium cyanoborohydride (24.5mg was added in one portion and the reaction stirred for a furthur 16 hours, The reaction was filtered and the filtrate evaporated in vacuo. The residue was partitio between CH2CI2 and sat Na 2 C0 3 and extracted into CH2CI2. The organic extracts were dried, (MgS0 4 ) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, gradient elution with 2-5% MeOH in CH2CI2). The product was converted to the hydrochloride salt. Anal. Calcd for C23H 2 3N 4 O 2 ClS-2.50 HC1-0.65 H 2 0 C, 56.77; H, 5.72; N, 11.03. Found: C, 56.74; H, 5.71 ; N, 10.81. IH NMR CD3OD δ 9.04(lH,s), 7.75(2H,d, J=7.9Hz), 7.65(lH,s), 7.60-7.40(5H), 7.26(lH,s), 4.33(2H,s), 4.27(2H,s), 4.11(2H,d, J=7.1 Hz), 3.50 (2H,d, J=8.1Hz), 3.00(2H,t, 11.9Hz), 2.17(lH,m), 1.90- 1.80(2H,m), 1.80-1.60(2H,m) ppm. EXAMPLE 123 2-[3-(4-cyanobenzyl)-3H-imidazol-l-yl]-N-(l-phenylpiperidin-4- yPacetamide hydrochloride StepA: 8-Phenyl- 1 ,4-dioxa-8-azaspiror4.51decane Palladium (II) chloride (1.40 g, 7.9 mmol) and tri-6>- tolylphosphine (4.80 g, 15.8 mmol) were stirred in dry toluene (60 mL) at room temperature under an argon atmosphere for 30 min. The solution was then diluted with dry toluene (800 mL) and to this was added l,4-dioxa-8-azaspiro[4.5]decane (27.4 g, 191 mmol); sodium tert- butoxide (21.4 g, 223 mmol); and bromobenzene (25.0 g, 159 mmol). The mixture was heated to 100 °C for 18 hrs then allowed to cool. Ether (300 mL) was added and the mixture was washed with brine (800 mL). The brine was extracted with a further portion of ether (200 mL) and the combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo to give a dark oil. The crude product was purified by flash column chromatography on silica, eluting with hexane - 10% ethyl acetate to yield the product as a pale yellow oil. Η NMR (CDCI 3 ) δ 7.25 (2H, dd, J=8,7Hz); 6.95 (2H, d, J=8Hz); 6.83 (IH, t, J=7Hz); 3.99 (4H, s); 3.32 (4H, m); 1.84 (4H, m). Step B: 1 -Phenylpiperidin-4-one 8-Phenyl-l,4-dioxa-8-azaspiro[4.5]decane (18.1 g, 82.5 mmol) was dissolved in a mixture of acetic acid (150 mL), water (150 mL), and cone, hydrochloric acid (38 mL) and the resulting solution was heated to 50 °C for 18 hrs. The reaction mixture was cooled in an ice-water bath, and sodium hydroxide pellets were added in portions until the mixture was neutralized. This mixture was extracted with dichloromethane (3 x 300 mL) and the combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo to give a dark oil. Chromatography on silica gel, eluting with hexane - 10% ethyl acetate gave the product as a pale yellow oil. Η NMR (CDC1 3 ) δ 7.30 (2H, dd, J=9,7Hz); 6.99 (2H, dd, J=9, lHz); 6.89 (IH, tt, J=7,lHz); 3.61 (4H, t, J=6Hz); 2.56 (4H, t, J=6Hz). Step C: 1 -Phenylpiperidin-4-ylamine l-Phenylpiperidin-4-one (3.0 g, 17.1 mmol) was dissolved in methanol (250 mL) and acetic acid (147 mL), and ammonium acetate (67 g, 870 mmol) was added portionwise. The mixture was stirred for 4 hrs at room temperature, then cooled to 0 °C (ice-water) and sodium cyanoborohydride (1.6 g, 25 mmol) was added, then the reaction mixture was stirred at room temperature for 18 hrs. Water (20 mL) was added, and the mixture was concentrated under reduced pressure. The residue was adjusted to pH 12 with 15% aqueous NaOH and the resulting mixture was extracted with dichloromethane (3 x 100 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with dichloromethane - 3% methanol - 0.3% NH 4 OH to give the product as a pale solid. Η NMR (CDCI 3 ) δ 7.26 (2H, m); 6.96 (2H, m); 6.83 ( IH, m); 3.65 (2H, m); 2.87-2.75 (3H, m); 1.92 (2H, m); 1.50 (2H, m); 1.32 (2H, br s). FAB MS: 177 (MH + ). Step D: 2-[3-(4-Cyanobenzyl)-3H-imidazol- 1 -yl]-N-( 1 - phenylρiperidin-4-yPacetamide hydrochloride 1 -Phenylpiperidin-4-ylamine (40 mg, 0.227 mmol), lithium [3-(4-cyanobenzyl)-3H-imidazol-4-yl]acetate (56 mg, 0.227 mmol), 1 - hydroxybenzotriazole hydrate (46 mg, 0.34 mmol), l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (87 mg, 0.45 mmol), and N,N-diisopropylethylamine (99 μL, 0.57 mmol) were added to degassed DMF (2 mL) and the mixture was stirred for 18 hrs at room temperature then concentrated in vacuo. The residue was added to sat. NaHC0 3 (aq) (5 mL) and extracted with dichloromethane (3 x 3 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with dichloromethane - 5% methanol - 0.05% NH 4 OH to give the product as a free base. This was lyophilized from HCl (aq) - acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C 24 H 25 N 5 0- 1.2 HC1-0.5 H 2 O-0.15 CH 2 C1 2 : C: 62.37; H: 5.96; N: 15.06 Found: C: 62.64; H: 6.35; N: 14.67 Η NMR (CD 3 OD) δ 8.79 (IH, d, J=lHz); 7.79 (2H, d, J=8Hz); 7.47- 7.40 (3H, m); 7.23 (2H, dd, J=7,9Hz); 7.00 (2H, d, J=8Hz); 6.86 (IH, t, J=7Hz); 5.55 (2H, s); 3.70-3.57 (3H, m); 3.60 (2H, s); 2.83 (2H, td, J=12,2Hz); 1.92 (2H, dd, J=14,4Hz); 1.59 (2H, qd, J=12,4Hz). FAB MS: 400 (MH + ). EXAMPLE 124 2-[3-(4-cyanobenzyl)-3H-imidazol-l-yl]-N-benzyl-N-(l- phenylpiperidin-4-yPacetamide hydrochloride Step A: Benzyl(l-phenylpiperidin-4-yl)amine 1 -Phenylpiperidin-4-one (2.0 g, 11.4 mmol) (from Example 123) and benzylamine (1.33 g, 12.5 mmol) were dissolved in 1 ,2-dichloroethane (35 mL) and acetic acid (1.36 g, 22.6 mmol) was added. The mixture was stirred for 2 hrs at room temperature, then cooled to 0 °C (ice-water) and sodium triacetoxyborohydride (3.14 g, 14.8 mmol) was added, then the reaction mixture was stirred at room temperature for 18 hrs. Sat. NaHC0 3 (aq) (30 mL) was added, and the organic layer was extracted. The aqueous phase was extracted with dichloromethane (2 x 50 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with hexane - 30% ethyl acetate to give the product as a white solid. Η NMR (CDC1 3 ) δ 7.35-7.21 (7H, m); 6.94 (2H, dd, J=9,lHz); 6.82 (IH, tt, J=7,lHz); 3.86 (2H, s); 3.66 (2H, dt, J=13,3Hz); 2.78 (2H, td, J=12,2Hz); 2.68 (IH, tt, J=10,4Hz); 2.01 (2H, m); 1.55 (2H, qd, J=12,4Hz); 1.35 (I H, br s). Step B: 2-[3-(4-cyanobenzyl)-3H-imidazol- l -yl]-N-benzyl-N-(l- phenylpiperidin-4-yl)acetamide hydrochloride Benzyl(l-phenylpiperidin-4-yl)amine (50 mg, 0.188 mmol), lithium [3-(4-cyanobenzyl)-3H-imidazol-4-yl]acetate (51 mg, 0.206 mmol), 1-hydroxybenzotriazole hydrate (38 mg, 0.28 mmol), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.38 mmol), and N,N-diisopropylethylamine (82 μL, 0.47 mmol) were added to degassed DMF (2 mL) and the mixture was stirred for 18 hrs at room temperature then concentrated in vacuo. The residue was added to sat. NaHC0 3 (aq) (5 mL) and extracted with dichloromethane (3 x 3 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with dichloromethane - 4% methanol - 0.01 % NH 4 OH to give the product as a free base. This was lyophilized from HCl (aq) - acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C 31 H 31 N 5 0-1.2 HC1-0.35 H 2 O-0.15 CH 2 C1 2 : C: 67.72; H: 6.06; N: 12.68 Found: C: 67.87; H: 6.39; N: 12.28 Η NMR (CD 3 OD) δ 8.88-8.86 (IH, m); 7.81 -7.69 (2H, m); 7.55-7.19 (10H, m); 7.00-6.97 (2H, m); 6.86 (IH, t, J=7Hz); 5.51-5.46 (2H, m); 4.63-4.59 (2H, m); 4.52-3.67 (5H, m); 2.86-2.76 (2H, m); 1.95- 1.73 (4H, m). FAB MS: 490 (MH + ). EXAMPLE 125 2-[3-(4-Cyanobenzyl)-3H-imidazol- 1 -yl]-N-( 1 -phenylpiperidin-4-yl)- N-pyridin-4-ylmethylacetamide hydrochloride The title compound was prepared according to the procedure in Example 124, Steps A & B, with 4-(aminomethyl)pyridine replacing benzylamine in Step A. The product was treated with HCl in ethyl acetate - ethanol to give the hydrochloride salt. Elemental analysis calculated for C 30 H 30 N 6 O-3 HC1-0.5 EtOH-0.5 CH 2 C1 2 : C: 56.85; H: 5.60; N: 12.63 Found: C: 57.00; H: 5.92; N: 12.80 FAB MS: 491 (MH + ). EXAMPLE 126 2-[3-(4-cyanobenzyl)-3H-imidazol- 1 -yl]-N-phenethyl-N-( 1 - phenylpiperidin-4-yPacetamide hydrochloride The title compound was prepared according to the procedure in Example 124, Steps A & B, with phenethylamine replacing benzylamine in Step A. The product was treated with HCl in ethyl acetate to give the hydrochloride salt. Elemental analysis calculated for C 32 H 33 N 5 0-2 HC1-0.2 H 2 0: C: 66.24; H: 6.15; N: 12.07 Found: C: 66.24; H: 5.91 ; N: 11.84 FAB MS: 504 (MH + ). EXAMPLE 127 4- { 5- [( 1 -Phenylpiperidin-4-ylamino)methyl] imidazol- 1 - ylmethyl } benzonitrile hydrochloride Step A: 4- { 5-[( 1 -Phenylpiperidin-4-ylamino)methyl]imidazol- 1 - ylmethyl } benzonitrile hydrochloride 1 -Phenylpiperidin-4-ylamine (75 mg, 0.43 mmol) (from Example 123) and 4-(5-formylimidazol-l-ylmethyl)benzonitrile (99 mg, 0.47 mmol) were dissolved in 1 ,2-dichloroethane (2 L) and acetic acid (49 μL, 0.86 mmol) was added. The mixture was stirred for 2 hrs at room temperature, then sodium triacetoxyborohydride (1 17 mg, 0.55 mmol) was added, then the reaction mixture was stirred at room temperature for 18 hrs. Sat. NaHC0 3 (aq) (30 mL) was added, and the organic layer was extracted. The aqueous phase was extracted with dichloromethane (2 x 5 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with dichloromethane - 5% methanol - 0.5% NH 4 OH to give the product as a free base. This was lyophilized from HCl (aq) - acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C_ 3 H 25 N 5 -2 HCl: C: 62.41 ; H: 6.14; N: 15.82 Found: C: 62.43; H: 6.02; N: 15.63 Η NMR (CD 3 OD) δ 8.62 (IH, s); 7.82 (2H, d, J=8Hz); 7.69 (IH, s); 7.46 (2H, d, J=8Hz); 7.27 (2H, t, J=8Hz); 7.06 (2H, d, J=8Hz); 6.92 (IH, t, J=8Hz); 5.67 (2H, s); 4.32 (2H, s); 3.82 (2H, d, J=13Hz); 3.40 (IH, tt, J=12,4Hz); 2.88 (2H, t, J=12Hz); 2.23 (2H, d, J=12Hz); 1.84 (2H, qd, J=12,4Hz). FAB MS: 372 (MH + ). EXAMPLE 128 4-(5-{ [Benzyl(l-phenylpiperidin-4-yl)amino]methyl } imidazol- 1- ylmethyPbenzonitrile hydrochloride The title compound was prepared according to the procedure in Example 127, Step A, with benzyl(l-phenylpiperidin-4- ypamine (from Example 124) replacing l-phenyIpiperidin-4-ylamine. The product was lyophilized from HCl (aq) - acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C 30 H 31 N 5 -HCl-0.4 EtOAc: C: 71.16; H: 6.65; N: 13.13 Found: C: 71.25; H: 6.47; N: 12.84 FAB MS: 462 (MH + ). EXAMPLE 129 4-(5- { [( 1 -phenylpiperidin-4-yl)pyridin-4- ylmethylamino]methyl } imidazol- 1 -ylmethyl)benzonitrile hydrochloride The title compound was prepared according to the procedure in Example 127, Step A, with (l-phenylpiperidin-4- yl)pyridin-4-ylmethylamine (from Example 125) replacing 1- phenylpiperidin-4-ylamine. The product was treated with HCl in ethyl acetate - ethanol to give the title compound as a white solid. Elemental analysis calculated for C 29 H 3 N 6 -4 HC1-0.65 EtOAc-0.6 H 2 0: C: 56.10; H: 6.02; N: 12.42 Found: C: 56.1 1 ; H: 6.02; N: 12.40 FAB MS: 463 (MH + ). EX AMPLE 130 4-(5- { [Phenethyl( 1 -phenylpiperidin-4-yl)amino]methyl } imidazol- 1 - ylmethvPbenzonitrile hydrochloride The title compound was prepared according to the procedure in Example 127, Step A, with phenethyl(l-phenylpiperidin-4- yl)amine (from Example 126) replacing l-phenylpiperidin-4-ylamine. The product was treated with HCl in ethyl acetate to give the title compound as a white solid. Elemental analysis calculated for C 31 H 33 N 5 -3 HC1-0.65 H 2 O-0.3 EtOAc: C: 61.42; H: 6.82; N: 11.60 Found: C: 61.42; H: 6.68; N: 11.53 FAB MS: 476 (MH + ). EXAMPLE 131 4- { 5-[2-( 1 -Phenylpiperidin-4-ylamino)ethyl]imidazol- 1 - ylmethyl } benzonitrile hydrochloride Step A: 4-{ 5-[2-(l-Phenylpiperidin-4-ylamino)ethyl]imidazol-l- ylmethyl } benzonitrile hydrochloride 1 -Phenylpiperidin-4-one (150 mg, 0.86 mmol) (from Example 123) and 4-[5-(2-aminoethyl)imidazol-l-ylmethyl]benzonitrile (213 mg, 0.94 mmol) were dissolved in 1 ,2-dichloroethane (4 mL) and acetic acid (49 μL, 0.86 mmol) was added. The mixture was stirred for 30 min at room temperature, then sodium triacetoxyborohydride (272 mg, 1.28 mmol) was added and the reaction mixture was stirred at room temperature for 18 hrs. Sat. Na 2 C0 3 (aq) (5 mL) was added, and the mixture was extracted with dichloromethane (3 x 10 mL). The combined organic extracts were dried over Na 2 S0 4 , filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with a gradient of dichloromethane - 0.5% NH 4 OH - 1 to 8% methanol to yield the product. Η NMR (CDC1 3 ) δ 7.63 (2H, d, J=8Hz); 7.51 (IH, s); 7.24 (2H, dd, J=9,7Hz); 7.12 (2H, d, J=8Hz); 6.93 (IH, s); 6.92 (2H, d, J=9Hz); 6.82 (IH, t, J=7Hz); 5.20 (2H, s); 3.63 (2H, dt, J=13,3Hz); 2.86 (2H, t, J=7Hz); 2.74 (2H, td, J=12,2Hz); 2.61 (2H, t, J=7Hz); 2.60-2.54 (IH, m); 2.10 (IH, br s); 1.92 (2H, d, J=13Hz); 1.46 (2H, qd, J=12,4Hz). Treatment with HCl in ethyl acetate gave the title compound as a white solid. Elemental analysis calculated for C 24 H 27 N 5 -3 HC1-0.5 EtOAc: C: 57.94; H: 6.36; N: 13.00 Found: C: 57.80; H: 6.42; N: 13.00 FAB MS: 386 (MH + ). EXAMPLE 132 4-(5- { 2- [Benzyl( 1 -phenylpiperidin-4-yl)amino]ethyl } imidazol- 1 - ylmethyPbenzonitrile hydrochloride Step A: 4-(5-{2-[Benzyl(l-phenylpiperidin-4- yl)amino]ethyl } imidazol- 1 -ylmethyPbenzonitrile hydrochloride Benzaldehyde (15 μL, 0.14 mmol) and 4-{5-[2-(l- phenylpiperidin-4-ylamino)ethyl]imidazol- 1 -ylmethyl } benzonitrile (50 mg, 0.13 mmol) (from Example 131 ) were dissolved in 1 ,2- dichloroethane (0.8 mL) and acetic acid (7 μL, 0.13 mmol) was added. The mixture was stirred for 30 min at room temperature, then sodium triacetoxyborohydride (41 mg, 0.20 mmol) was added and the reaction mixture was stirred at room temperature for 18 hrs. Sat. Na 2 C0 3 (aq) (3 mL) was added, and the mixture was extracted with dichloromethane (3 x 5 mL). The combined organic extracts were dried over Na 2 S0 4 , filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with a gradient of ethyl acetate - 0 to 10% methanol to yield the product. Η NMR (CDC1 3 ) δ 7.55 (2H, d, J=8Hz); 7.40 (IH, d, J=lHz); 7.29-7.21 (7H, m); 6.94-6.90 (4H, m); 6.86 (IH, s); 6.83 (IH, tt, J=7, lHz); 4.86 (2H, s); 3.72 (2H, d, J=12Hz); 3.62 (2H, s); 2.71-2.60 (5H, m); 2.39 (2H, t, J=8Hz); 1.83 (2H, d, J=12Hz); 1.68 (2H, qd, J=12,4Hz). Treatment with HCl in ethyl acetate gave the title compound as a white solid. Elemental analysis calculated for C 31 H 33 N 5 -3 HC1-0.3 H 2 O-0.15 EtOAc: C: 62.87; H: 6.31; N: 11.60 Found: C: 62.87; H: 6.14; N: 1 1.60 FAB MS: 476 (MH + ). EXAMPLE 133 2-[3-(4-cyanobenzyl)-3H-imidazol-l-yl]-N-(4-cyanobenzyl)-N-(l- phenylpiperidin-4-yPacetamide hydrochloride Step A: 4-Cyanobenzyl( 1 -pheny lpiperidin-4-yPamine 1 -Phenylpiperidin-4-ylamine (0.50 g, 2.84 mmol) (from Example 123) and 4-cyanobenzaldehyde (0.74 g, 5.64 mmol) were dissolved in anhydrous methanol (10 mL) and acetic acid (0.97 mL, 17 mmol) was added. The mixture was stirred for 2 hrs at room temperature, then cooled to 0 °C (ice-water) and sodium cyanoborohydride (0.267 g, 4.25 mmol) was added, then the reaction mixture was stirred at room temperature for 2 hrs. The solvent was evaporated under reduced pressure and the residue was partitioned between sat. NaHC0 3 (aq) (50 mL) and dichloromethane (25 mL), and the organic layer was extracted. The aqueous phase was extracted with dichloromethane (2 x 25 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with hexane - 30% ethyl acetate to give the product as a white solid. Η NMR (CDC1 3 ) δ 7.62 (2H, d); 7.48 (2H, d); 7.25 (2H, t); 6.94 (2H, d); 6.83 (IH, t); 3.93 (2H, s); 3.65 (2H, dt); 2.78 (2H, td); 2.65 (I H, tt); 1.99 (2H, d); 1.54 (2H, qd); 1.41 (IH, br s). Step B: 2-[3-(4-cyanobenzyl)-3H-imidazol- 1 -yl]-N-(4- cyanobenzyl)-N-( 1 -phenylpiperidin-4-yl)acetamide hydrochloride 4-Cyanobenzyl(l-phenylpiperidin-4-yl)amine (75 mg, 0.26 mmol), lithium [3-(4-cyanobenzyl)-3H-imidazol-4-yl]acetate (70 mg, 0.28 mmol), 1 -hydroxybenzotriazole hydrate (52 mg, 0.38 mmol), l -(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (99 mg, 0.52 mmol), and N,N-diisopropylethylamine (67 μL, 0.38 mmol) were added to degassed DMF (3 mL) and the mixture was stirred for 18 hrs at room temperature then concentrated in vacuo. The residue was added to sat. NaHC0 3 (aq) (5 mL) and extracted with dichloromethane (3 x 3 mL). The combined organic extracts were dried over MgS0 4 , filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with dichloromethane - 2% methanol to give the product as a free base. This was lyophilized from HCl (aq) - acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C 32 H 30 N 6 O-2.5 HCl- 1.85 H 2 0: C: 60.04; H: 5.86; N: 13.13 Found: C: 60.08; H: 5.66; N: 13.09 Η NMR (CD 3 OD) δ 8.99-8.92 (IH, m); 7.81-7.40 ( 14H, m); 5.59-5.53 (2H, m); 4.86-4.66 (3H, m); 4.40-3.69 (6H, m); 2.55-2.42 (2H, m); 2.15-2.02 (2H, m). FAB MS: 515 (MH + ). EXAMPLE 134 N-(l -benzylpiperidin-4-yl)-2-[3-(4-cyanobenzyl)-3H-imidazol-4- yllacetamide hydrochloride The title compound was prepared according to the procedure in Example 123, Steps C & D, with 1 -benzylpiperidin-4-one replacing l-phenylpiperidin-4-one in Step C. The product was treated with HCl in ethyl acetate - ethanol to give the hydrochloride salt. Elemental analysis calculated for C 25 H 27 N 5 0-2 HCl-1 MeOH: C: 60.22; H: 6.42; N: 13.51 Found: C: 60.07; H: 6.53; N: 13.27 FAB MS: 414 (MH + ). EXAMPLE 135 4- { 5-[( 1 -benzylpiperidin-4-ylamino)methyl]imidazol- 1 - ylmethyl } benzonitrile hydrochloride To a stirred solution of l-benzylpiperidin-4-ylamine (38 mg, 0.20 mmol) (from Example 134) and 4-(5-formylimidazol-l- ylmethyPbenzonitrile (42 mg, 0.20 mmol) in methanol (1 mL) was added sodium cyanoborohydride (12 mg, 0.20 mmol). Acetic acid was added to adjust the mixture to pH 5.5, as judged by analyzing the solution with moist indicator paper. The resulting solution was stirred for 18 hrs, then sat. Na 2 C0 3 (aq) (5 mL) was added and the mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were washed with water (10 mL), then brine (10 mL), then dried over Na 2 S0 4 , filtered and concentrated in vacuo. The residue was chromatographed on silica, eluting with ammonia-saturated chloroform to give the product as a free base. Η NMR (CDC1 3 ) δ 7.61 (2H, d); 7.49 (IH, s); 7.48 (2H, d); 7.33-7.22 (5H, m); 7.15 (2H, d); 6.95 (IH, s); 5.37 (2H, s); 3.59 (2H, s); 3.47 (2H, s); 2.78 (2H, d); 2.39 (IH, tt); 1.98 (2H, td); 1.73 (2H, d); 1.32 (2H, m); 1.41 (IH, br s). Treatment of this with HCl in ethyl acetate - ethanol gave the hydrochloride salt. Elemental analysis calculated for C 24 H 27 N 5 -3 HCl- 1 EtOH-0.4 CH 2 C1 2 : C: 55.15; H: 6.45; N: 12.18 Found: C: 55.29; H: 6.59; N: 12.02 FAB MS: 386 (MH + ). EXAMPLE 136 In vitro inhibition of ras farnesyl transferase Assays of farnesyl-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 31:3800 (1992) and Gibbs et al., PNAS U.S.A. 86:6630-6634 (1989), respectively. Bovine FPTase was assayed in a volume of 100 μl containing 100 mM N-{2- hydroxy ethyl) piperazine-N'-(2-ethane sulfonic acid) (HEPES), pH 7.4, 5 mM MgCl2, 5 mM dithiothreitol (DTT), 100 mM [3H]-farnesyl diphosphate ([3H]-FPP; 740 CBq/mmol, New England Nuclear), 650 nM Ras-CVLS and 10 μg/ml FPTase at 31°C for 60 min. Reactions were initiated with FPTase and stopped with 1 ml of 1.0 M HCL in ethanol. Precipitates were collected onto filter-mats using a TomTec Mach II cell harvestor, washed with 100% ethanol, dried and counted in an LKB β-plate counter. The assay was linear with respect to both substrates, FPTase levels and time; less than 10% of the [3H]-FPP was utilized during the reaction period. Purified compounds were dissolved in 100% dimethyl sulfoxide (DMSO) and were diluted 20-fold into the assay. Percentage inhibition is measured by the amount of incorporation of 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 nM 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 described in above Examples 1-135, except for Example U2C, were tested for inhibitory activity against human FPTase by the assay described above and were found to have IC50 of ≤50 μM. EXAMPLE 31 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 :712-717, (1991). Cells in 10 cm dishes at 50-75% confluency are treated with the test compound (final concentration of solvent, methanol or dimethyl sulfoxide, is 0.1 %). After 4 hours at 37°C, the cells are labelled in 3 ml methionine-free DMEM supple- meted with 10% regular DMEM, 2% fetal bovine serum and 400 mCi[35S]methionine (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 al-, J- Virol. 43:294-304, (1982)). Following a 2 hour antibody incubation at 4°C, 200 ml of a 25% suspension of protein A-Sepharose coated with rabbit anti rat IgG is added for 45 min. The immunoprecipitates are washed four times with IP buffer (20 nM HEPES, pH 7.5/1 mM EDTA/1 % Triton X- 100.0.5% deoxycholate/0.1 %/SDS/0.1 M NaCl) boiled in SDS-PAGE sample buffer and loaded on 13% acrylamide gels. When the dye front reached the bottom, the gel is fixed, soaked in Enlightening, dried and autoradiographed. The intensities of the bands corresponding to farnesylated and nonfarnesylated ras proteins are compared to determine the percent inhibition of farnesyl transfer to protein. EXAMPLE 32 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 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 containing 0.1% methanol or the concentration of the instant compound. Photomicrographs are taken 16 days after the cultures are seeded and comparisons are made.

Claims: WHAT IS CLAIMED IS: 1. A compound which inhibits farnesyl-protein transferase of the formula A: wherein: Rla and RΪb are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, RlOO-, R 1 ] S(0) m -, R10C(O)NR10_, (Rl0) 2 N-C(O)-, CN, N02, (R 10 )2N-C(NRlO)-, RlOc(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-, c) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R^O-, R π S(0)m-, R 10 C(O)NRl0-, (RlO) 2 N-C(0)-, CN, (RlO)2N-C(NRlO)-, RlOc(O)-, N3, -N(RlO)2, and Rl lθC(O)-NRl0- ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C 1 -C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, R n S(0) m -, R 10 C(O)NRl0-, (R10)2N-C(0)-, CN, (R1°)2N-C(NR10)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO)2, and Rl lθC(O)-NRl0-, and c) unsubstituted or substituted aryl; R2 and R3 are independently selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, OR 10, wherein the substituted group is substituted with one or more of: 1 ) aryl or heterocycle, unsubstituted or substituted with: a) Cl -4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Ci-4 alkyl, h) SR6a S(0)R 6a , S02R 6a , 2) C3-6 cycloalkyl, 3) OR6 4) SR6 , S(0)R6a 0 r Sθ2R 6a , 5) — NR 6 R 7 15) N 3 , 16) F, or 17) perfluoro-C^-alkyl; or R2 and R3 are attached to the same C atom and are combined to form - (CH2)u - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0) m , -NC(O)-, and -N(CORlO)- ; R4 and R^ are independently selected from H and CH3; and any two of R^, R3, R4 an( j R5 are optionally attached to the same carbon atom; R6, R7 and R^a are independently selected from: H; C 1 -4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) unsubstituted aryl, substituted aryl, unsubstituted heteroaryl or substituted heterocycle, c) halogen, d) HO, f) — S0 2 R 1 1 , or R6 and R^ may be joined in a ring; R7 and R^a may be joined in a ring; R6a i s selected from: Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, f) — S0 2 R 11 , or g) N(RlO) 2 ; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C 10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, perfluoroalkyl, F, Cl, Br, RK>0-, R lS(0) m - RlOC(0)NRlO-, (Rl0) 2 NC(O)-, Rlθ2N-C(NRlO)-, CN, NO2, R 10 C(O)-, N3, -N(Rl ) 2 , or RHOC(O)NR 10-, and c) Cl-C6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, Rl O-, R n S(0)m-, Rl°C(0)NH-, (Rl0)2NC(O)-, Rl0 2 N- C(NRlO)-, CN, RlOC(O)-, N3, -N(R lO) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(O) m -, Rl0C(O)NRl0-, (Rl0) 2 NC(O)-, R 10 2 N-C(NR10)-, CN, N02, R 10 C(O)-, N3, -N(Rl ) 2 , or Rl lθC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOO-, RHS(0) m -, R 10 C(O)NRl0-, (Rl0) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(Rl )2, or RH OC(O)NR10- ; RI is independently selected from hydrogen, C1 -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; R 2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, substituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl -4 alkyl, b) (CH2)pOR6 d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Cl-4 alkyl, h) SR6a, S(0)R6a Sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR 6 , 4) SR6 , S(0)R6a, or Sθ2R 6a , 5) — NR 6 R 7 8) " O γ R 6 R 7 O 9) ~ O^ .OR 6 T O 10) \ ^NR 6 R 7 O 11) — S0 2 -NR 6 R 7 12) — N-S0 2 -R 6a 13) O 14) OR fc o 15) N 3 , 16) F, 17) perfluoro-Cι -4 -alkyl, or 18) C 1 -6 -alkyl; Al and A2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRl OC(O)-, O, -N(R10)-, -S(0)2N(Rl )-, -N(Rl )S(0)2-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C 1 -C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, provided that V is not hydrogen if A^ is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A2 is S(0)m, W is a heterocycle; X is a bond, -CH2-, -C(=0)-, -NR 0 C(=0)- or -S(=0) m -; X I is a bond, -C(=0)-, -NR θ C(=0)-, -NR°-, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOO-, Rl lS(0) m -, R 10 C(O)NRl0-, (Rl 0) 2 N-C(O)-, CN, N02, (RlO)2N-C(NRlO)-, Rl2c(0)-, Rl OθC(O)-, N3, F, -N(Rl ) 2 , or RHθC(O)NRl0-, and c) unsubstituted or substituted C]-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, Rl°0-, Rl0c(O)NR 0-, (RlO) 2 N-C(0)-, RlOC(O)- and RIOQC(O)-; or a pharmaceutically acceptable salt thereof. 2. A compound which inhibits farnesyl-protein transferase of the formula B: B wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, Rl O-, Rl lS(0) m -, R!0C(O)NR10-, (RlO) 2 N-C(0)-, CN, Nθ2, (RlO)2N-C(NRlO)-, R10C(O)-, N3, -N(RlO)2, or Rl 10C(0)NR10-, c) unsubstituted or substituted Cl -C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl0< , Rl lS(0)m-, Rlθ O)NRlO-, (Rl ) 2 N-C(0)-, CN, (RlO) N-C(NRlO)-, RlOc(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10-; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted Cl-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, R U S(0)m-, Rl0C(O)NRl0-, (RlO) 2 N-C(0)-, CN, (R10) 2 N-C(NR 0)-, RlOc(O)-, Rl θC(O)-, N3, -N(Rl ) , and R11OC(O)-NR10-, an d c) unsubstituted or substituted aryl; R2 and R3 are independently selected from: H; unsubstituted or substituted Cl -8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, OR 10, O O wherein the substituted group is substituted with one or more of: 1 ) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Cl-4 alkyl, h) SR6 S(0)R6a, Sθ2R 6 2) C3-6 cycloalkyl, 3) OR6, 4) SR6a, S(0)R6a, or Sθ2R 6a 6r>7 5) NR°R ■ O ^ .NR 6 R 7 8) T o 9) Ό^.OR 6 T o o 11) — S0 2 -NR 6 R 7 13) ^ R£ O 14 > -X 0R6 o 15) N 3 , 16) F, or 17) perfluoro-C^-alkyl; or R2 and R3 are attached to the same C atom and are combined to form - (CH2)u - wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(0) m , -NC(O)-, and -N(CORlO)- ; R4 and R5 are independently selected from H and CH3; and any two of R2, R3 ? R4 an( j R5 are optionally attached to the same carbon atom; R6, R7 and R^a are independently selected from: H; Cl -4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) unsubstituted aryl, substituted aryl, unsubstituted heteroaryl or substituted heterocycle, c) halogen, d) HO, f) — S0 2 R 11 , or g) N(RlO) 2 ; or R6 and R7 may be joined in a ring; R7 and R^a may be joined in a ring; R6a is selected from: Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, R 11 e) O f) — S0 2 R 11 , or g) N(RlO) 2; R8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, perfluoroalkyl, F, Cl, Br, RlOo-, Rl l S(0) m -, R!0C(O)NR10-, (RlO) 2 NC(0)-, Rl°2N-C(NRl )-, CN, N02, Rl°C(0)-, N3, -N(RlO)2, or RH OC(O)NR1 -, an d c) C 1 -C6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, Rl O-, R H S(0)m-, Rl0C(O)NH-, (Rl0) 2 NC(O)-, R10 2 N- C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , or Rl0θC(O)NH-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, R OO-, Rl lS(0)m-, R 10 C(O)NRl0-, (Rl0) 2 NC(O)-, R10 2 N-C(NR10)-, CN, Nθ2, R 10 C(O)-, N3, -N(RlO) 2 , or RHOC(O)NR10-, and c) C 1-C6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, RlOo-, Rl lS(0) m -, R!0C(O)NR10-, (Rl0) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, RIOC(O)-, N3, -N(RlO)2, or Rl lθC(O)NRl0-; RlO is independently selected from hydrogen, C1-C 14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; R! 1 is independently selected from Cl-C6 alkyl and substituted or unsubstituted aryl; A and A 2 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 ; 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 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 2 is S(0)m; W is a heterocycle; X 2 is a bond, -CH2-, -C(=0)-, -NR°C(=0)-, -C(=0)NR6-, -NR6-, -O- or -S(=0) m -; Z is an unsubstituted or substituted group selected from aryl and heterocycle, wherein the substituted group is substituted with one or more of the following: 1) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NROR7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R6a, or g) -C(0)NR6R7, 2) aryl or heterocycle, or a pharmaceutically acceptable salt thereof. 3. The compound according to Claim 1 of the formula A: wherein: Rl is independently selected from: hydrogen or Cl-C6 alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloafkyl, Rl°0-, -N(Rl ) 2 or C2-C6 alkenyl, c) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO- and -N(RlO) 2; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted C 1-C6 alkyl wherein the substitutent on the substituted Cj-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C 2 -C6 alkenyl, C2-C6 alkynyl, RlOO-, R U S(0) m -, Rl0C(O)NRl0-, (RlO) 2 N-C(0)-, CN, (Rl0)2N-C(NRl0)-, RI C(O)-, RlOθC(O)-, N3, -N(Rl°)2, and RHOC(O)-NR10-, and c) unsubstituted or substituted aryl; R3, R4 and R^ are independently selected from H and CH3; \ .NR 6 R 7 T ; R is H; ORl0, O or C 1 -5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR6, 4) SR 6a , Sθ2R 6a , or 5 ) \ .NR 6 R 7 O and any two of R 2 , R3, R4, and R5 are optionally attached to the same carbon atom; R6, R7 and R7a are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6a is selected from: Cl -4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -C6 perfluoroalkyl, F, Cl, RlOO-, R10C(O)NR1 -, CN, NO2, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(RlO) , or RHOC(O)NR 0-, and c) C1-C6 alkyl substituted by C1-C6 perfluoroalkyl, R Oo-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRlO)-, R10C(O)-, -N(Rl0) 2 , or Rl l OC(O)NRl0- ; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl lS(0)m-, R1°C(0)NR 10-, CN, NO2, (Rl0) 2 N-C(NRl0)-, RlOC(O)-, -N(Rl ) 2 , or Rl lθC(O)NRl0-, and c) Cl -C6 alkyl unsubstituted or substituted by C 1-C6 perfluoroalkyl, F, Cl, RlOO-, RHS(0) m -, R! C(O)NR10-, CN, (R O) 2 N-C(NRlO)-, RlOC(O)-, -N(RlO) 2 , or R1 OC(O)NR 0- ; R O is independently selected from hydrogen, C1-C 14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; Rl2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, suvbstituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) C] -4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-C 1 -4 alkyl, h) SR6a, S(0)Roa, Sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR6 4) SR6a, S(0)R6a, or Sθ2R 6a 6 D 7 5) NR b R 8) " γ NR 6 R 7 O 9) — O^ / OR 6 T o 10) ^NR 6 R 7 O 11) — S0 2 -NR 6 R 7 \ 12) — N-S0 2 -R 6a 13) 0 14) OR e o 15) N 3 , 16) F, 17) perfluoro-C 1- -alkyl, or 18) C^-alkyl; Al and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRI OC(O)-, 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, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C 1 -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 A is a bond, n is 0 and A 2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X is -CH2- or -C(=0)-; Xl is a bond, -C(=0)-, -NR6C(=0)-, -NR6-, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOO-, Rl lS(0)m-, R 1°C(0)NR 10-, (R10 )2N -C(O)-, CN, Nθ2, (Rl )2N-C(NRlO)-, R! 2C(0)-, RlOθC(O)-, N3, F, -N(Rl )2, or Rl 10C(0)NR 10-, and c) unsubstituted or substituted C 1 -C6 alkyl wherein the substitutent on the substituted C1 -C6 alkyl is selected from unsubstituted or substituted aryl, RlOO-, R! 0C(O)NR 10-, (RlO)2N-C(0)-, RlOC(O)- and RlOθC(O)-; Z is an unsubstituted or substituted group selected from aryl and heterocycle, wherein the substituted group is substituted with one or more of the following: I ) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R6a Q r g) -C(0)NR6R7, 2) aryl or heterocycle, 3) halogen, 4) OR 6 - 5) NROR7, 6) CN, 7) N02, 8) CF3; 9) -S(0) m R 6a , 10) -C(0)NR6R7, or I I ) C3-C6 cycloalkyl; or a pharmaceutically acceptable salt thereof. 4. The compound according to Claim 2 of the formula B: B wherein: Rla is independently selected from: hydrogen or Ci -C6 alkyl; R 1 b is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl O-, -N(R l°)2 or C2-C6 alkenyl, c) unsubstituted or substituted Cl-C6 alkyl wherein the substitutent on the substituted Cl-C6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO- and -N(RlO)2; R 1 c is selected from: a) hydrogen, b) unsubstituted or substituted C 1 -C6 alkyl wherein the substitutent on the substituted Cl-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RIOQ-, R π S(0)m-, Rl°C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (RlO)2N-C(NRlO)-, Rl Oc(O)-, RlOθC(O)-, N3, -N(Rl )2, and Rl 10C(0)-NR10-, and c) unsubstituted or substituted aryl; R3, R4 and R^ are independently selected from H and CH3; \ . NR 6 R 7 R 2 is H; T O ; or C 1-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR 6 , 4) SR6a, S02R 6a , or 5) ^ R 6 R 7 T O ; and any two of R 2 , R , R , and R^ are optionally attached to the same carbon atom; R6, R7 and R7a are independently selected from: H; Cl -4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R 6a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) C ] -4 alkoxy, b) halogen, or c) aryl or heterocycle; 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-, R10C(O)NR10-, CN, NO2, (RlO)2N-C(NRlO)-, RlOc(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, and c) C1-C6 alkyl substituted by -Cό perfluoroalkyl, Rl O-, RlOC(0)NR O-, (R10) 2 N-C(NR 10)-, RlOc(O)-, -N(RlO) 2 , or Rl lθC(O)NRl0-; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOo-, Rl lS(0) m -, R10C(O)NR1 -, CN, NO2, (RlO) 2 N-C(NRlO)-, RlOC(O)-, -N(Rl0)2, or Rl lOC(O)NRl0-, and c) C1-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, RlOO-, Rl l S(0) m -, R1 C(O)NR 1 -, CN, (R1 ) 2 N-C(NR10)-, R l Oc(O)-, -N(Rl ) 2 , or RHOC(O)NR10- ; R O is independently selected from hydrogen, -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; A l and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(0)-, -C(O)NRl 0-, -NR IOC(O)-, 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, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C 1 -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, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if A 1 is a bond, n is 0 and A 2 is S(0)m; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X 2 is a bond, -CH2-, -C(=0)-, -NR 0 C(=0)-, -C(=0)NR6-, -NR G -, -O- or -S(=0)mS Z is an unsubstituted or substituted aryl , wherein the substituted aryl is substituted with one or more of the following: 1) C l -4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R6a, or g) -C(0)NR6R7, 2) aryl or heterocycle, or a pharmaceutically acceptable salt thereof. 5. The compound according to Claim 1 of the formula C: wherein: Rla is selected from: hydrogen or C 1-C6 alkyl; Rlb is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(RlO) 2 or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, or -N(RlO) 2; R 1 c is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R lOO-, Rl lS(0)m-, R! 0C(O)NR10-, (RlO) 2 N-C(0)-, CN, (R10) 2 N-C(NR10)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO) 2 , and RHOC(0)-NR10-, and c) unsubstituted or substituted aryl; R and R independently selected from H and CH3; \ . NR 6 R 7 R 2 is selected from H; ORlO; T O ; or Cl-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR 6 , 4) SR6a, S02R 6a , or 5) ^ . NR 6 R 7 O and R 2 , R3 and R4 are optionally attached to the same carbon atom; R6 and R7 are independently selected from: H; Cl-4 alkyl, C3_6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R°a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R is independently selected from: a) hydrogen, b) Cl -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, RlOO-, R 10C(O)NR 10-, CN, NO2, (RlO)2N-C(NRlO)-, RlOC(O)-, -N(RlO)2, or RH OC(O)NR10-, and c) C1-C6 alkyl substituted by Cl -Cό perfluoroalkyl, R l O-, Rl C(0)NRlO-, (RlO) 2 N-C(NRl )-, R H)C(O)-, -N(RlO) , or Rl lθC(O)NRl0-; R^a is hydrogen or methyl; R is independently selected from hydrogen, C1-C6 alkyl, benzyl and aryl; Rl 1 is independently selected from C1-C6 alkyl and aryl; R l 2 is selected from: H; unsubstituted or substituted Cl-8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, substituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, d) halogen, e) CN, f) aryl or heteroaryl, g) perfluoro-Cl-4 alkyl, h) SR° , S(0)R° a , Sθ2R 6a , 2) C3-6 cycloalkyl, 3) OR6, 4) SR6a, S(0)R 6 , or Sθ2R 6a , 5) — NR 6 R 7 7) — N NR 7 R 7a T O Al and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, 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, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C 1 -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 A is a bond, n is 0 and A 2 is S(0) m ; X is -CH2- or -C(=0)-; χl is a bond, -C(=0)-, -NR°C(=0)-, -NR 6 -, -O- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOo-, Rl lS(0) m -, R!0C(O)NR 10-, (R10) 2 N-C(0)-, CN, Nθ2, (RlO)2N-C(NRlO)-, Rl 2 C(0)-, RlOθC(O)-, N3, F, -N(RlO)2, or RHθC(O)NRl0-, c) unsubstituted or substituted C1 -C6 alkyl wherein the substitutent on the substituted C] -C6 alkyl is selected from unsubstituted or substituted aryl, R OO-, Rl0C(O)NRl0-, (RlO) 2 N-C(0)-, RlOC(O)- and RlOθC(O)-; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1) Cl -4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NROR7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R6a, or or a pharmaceutically acceptable salt thereof. 6. The compound according to Claim 2 of the formula D: wherein: Rla is selected from: hydrogen or C1-C6 alkyl; R b is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, Rl°0-, -N(RlO) 2 or C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, Rl O-, or -N(RlO) 2 ; Rlc is selected from: a) hydrogen, b) unsubstituted or substituted Cl -C6 alkyl wherein the substitutent on the substituted Cl-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 1 OO-, R 1 •SlO -, Rl°C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (R10) 2 N-C(NR10)-, R10C(O)-, RlOθC(O)-, N3, -N(RlO) 2 , and Rl 10C(0)-NR10-, and c) unsubstituted or substituted aryl; R3 and R4 independently selected from H and CH3; NR 6 R 7 R 2 is selected from H; OR O; O or Cl-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR 6 , 4) SR6a Sθ2R 6a , or 5 ) \ . NR 6 R 7 O and R 2 , R and R4 are optionally attached to the same carbon atom; R6 and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R6a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, RlOo-, R10C(O)NR10-, CN, N02, (RlO) 2 N-C(NRlO)-, RlOC(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, and c) C 1 -C6 alkyl substituted by C l -C6 perfluoroalkyl, R 1 θ- , Rl0C(O)NRl0-, (Rl0) 2 N-C(NRl0)-, R I O O)-, -N(Rl )2, or Rl lθC(O)NRl0- ; R9a i s hydrogen or methyl; RlO is independently selected from hydrogen, C 1 -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; A and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(R 10)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxoρiperidinyl, 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 Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A 2 is S(0)m; X 2 is a bond, -CH2-, -C(=0)-, -NR6c(=0)-, -C(=0)NR6-, -NR 6 -, -O- or -S(=0)m-; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1 ) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl, substituted aryl or heterocycle, e) HO, f) -S(0) m R 6 , or g) -C(0)NR6R7, 2) aryl or heterocycle, 3) halogen, 4) OR 6 ' 5) NR 6 R7, or a pharmaceutically acceptable salt thereof. 7. The compound according to Claim 1 of the formula wherein: Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R l°0-, -N(Rl 0) Q r C2-C6 alkenyl, c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, Rl Oo, or -N(RlO) 2 ; R c is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOo-, Rl lS(0)m-, RlOC(0)NRlO-, (R10) 2 N-C(O)-, CN, (RlO) 2 N-C(NRlO)-, RlOC(O)-, RlOθC(O)-, N3, -N(RlO) 2 , and Rl 10C(0)-NR 10-, and c) unsubstituted or substituted aryl; R and R4 independently selected from H and CH3 ; NR 6 R 7 R 2 is selected from H; ORl°; O or C 1-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR 6 , 4) SR 6 , S02R 6a or 5 ) \ ^ NR 6 R 7 T o ; and R 2 , R3 and R4 are optionally attached to the same carbon atom; R 6 , R7 and R7 are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl -4 alkoxy, b) halogen, or c) aryl or heterocycle; R is independently selected from: a) hydrogen, b) C 1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C l -Co perfluoroalkyl, F, Cl, RlOO-, R10C(O)NR 10-, CN, Nθ2, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(Rl ) 2 , or R HOC(O)NR10-, and c) C 1 -C6 alkyl substituted by C l -Cβ perfluoroalkyl, R 1 0 O-, Rl0C(O)NRl0-, (RlO) 2 N-C(NRl )-, RlOc(O)-, -N(RlO)2, or Rl lOC(O)NRl0- ; RlO is independently selected from hydrogen, C1 -C14 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; Rl 2 is selected from: H; unsubstituted or substituted Cl_8 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted alkyl, suvbstituted aryl or substituted heterocycle is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Cl-4 alkyl, b) halogen, c) CN, d) perfluoro-C 1 -4 alkyl, 2) C3-6 cycloalkyl, 3) OR 6 , 4) SR 6 , S(0)R a , or Sθ2R 6 , X is -CH2- or -C(=0)-; Xl is a bond, -C(=0)- or -S(=0) m -; Y is selected from: a) hydrogen, b) RlOO-, Rl lS(0) m -, R 10 C(O)NRl0-, (Rl0) 2 N-C(O)-, CN, N02, (RlO)2N-C(NRlO)-, Rl 2 C(0)-, RlOθC(O)-, N3, F, -N(RlO)2, or Rl 10C(0)NR10-, c) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, Rl OO-, R!0C(O)NR 0-, (RlO)2N-C(0)-, RlOC(O)- and RlOθC(O)-; Z is an unsubstituted or substituted aryl, wherein the substituted aryl is substituted with one or more of the following: 1) Cl-4 alkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, or a pharmaceutically acceptable salt thereof. 8. The compound according to Claim 2 of the formula wherein: Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R OO-, -N(R10) 2 or C2-C6 alkenyl, c) C 1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, RlOO-, or -N(RlO) 2 ; R 1 c is selected from: a) hydrogen, b) unsubstituted or substituted C1-C6 alkyl wherein the substitutent on the substituted C1-C6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 1 OO-, R n S(0) m -, Rl0c(O)NRl0-, (Rl0) 2 N-C(O)-, CN, (RlO)2N-C(NRlO)-, Rl Oc(O)-, RlOθC(O)-, N3, -N(RlO)2, and Rl 10C(0)-NR10-, and c) unsubstituted or substituted aryl; R and R4 independently selected from H and CH3; NR 6 R 7 R 2 is selected from H; ORl°; O or Ci-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 ) aryl, 2) heterocycle, 3) OR 6 , 4) SR 6a , Sθ2R 6a , or 5 ) \ NR 6 R 7 T o ; and R 2 , R3 and R4 are optionally attached to the same carbon atom; R 6 , R7 and R7a are independently selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R 6a is selected from: Cl-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) halogen, or c) aryl or heterocycle; R8 is independently selected from: a) hydrogen, b) C 1 -C6 alkyl , C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C6 perfluoroalkyl, F, Cl, Rl O-, R 10C(O)NR10-, CN, NO2, (R10)2N-C(NR 10)_, R10 C (O)-, RlOθC(O)-, -N(Rl ) 2 , or R lθC(O)NRl0-, and c) C1-C6 alkyl substituted by Cl -Cό perfluoroalkyl, RlOO-, R l0C(O)NRl0-, (RlO) 2 N-C(NRlO)_, RlOc(O)-, RlOθC(O)-, -N(RlO) , or Rl lθC(O)NRl0- ; RlO is independently selected from hydrogen, C l -C ]4 alkyl, substituted or unsubstituted benzyl and substituted or unsubstituted aryl; Rl 1 is independently selected from C1-C6 alkyl and substituted or unsubstituted aryl; X 2 is -CH2-, -C(=0)-, -C(=0)NR 6 - or -NR 6 -; or a pharmaceutically acceptable salt thereof. 9. The compound according to Claim 1 wherein χl is a bond. 10. The compound according to Claim 2 wherein X 2 is a bond, -CH2-, -C(=0)-, -NR 6 C(=0)-, -C(=0)NR 6 - or -S(=0) m -. 11. A compound which inhibits farnesyl-protein transferase which is: N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -4-(3-methylphenyl)- 4-hydroxy piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yllmethyl } -4-(3-chloropheny l)-4 hydroxy piperidine, N- { f 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl]methyl } -4-(2- methylbenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl } -4-(3-methyIphenyl)-4 hydroxy piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acety 1 } -4-(2- methylbenzyl)isonipecotic acid methyl ester, N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-yllacetyl }-4-(4- methylbenzyl))isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y IJacety 1 } -4-(3- methylbenzyl))isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yllacety I } -4-(2,4- dichlorobenzyl))isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yllacetyl } -4-(3- methoxybenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-ylJacetyl } -4-( 1 - naphthylmethyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } -4-(4- chlorobenzyl)isonipecotic acid methyl ester, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-y l]acetyl } -4-(2,3- dichlorobenzyl)isonipecotic acid methyl ester, N-{ l-(4 Cyanobenzyl)- lH-imidazol-5-yl-aminocarbonyl }-4-(2- methylbenzyl) isonipecotic acid methyl ester, 2(R,S)-N { -2- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]2-(4- cyanobenzyl) } acetyl-4-(2-methylbenzyl)-isonipecotic acid methyl ester, N- { [ 1 -(Naphth-2-ylmethyl)- 1 H-imidazol-5-yllacetyl } -4-(2- methylbenzyl)isonipecotic acid methyl ester, N-{ [ 1 -(4-Cyanobenzyl)- lH-imidazol-5-yl]methyl }-4-methoxymethyl-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acety 1 } — 4-methoxymethyl-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzy 1)- 1 H-imidazol-5-y lfacety 1 } -4-hydroxymethyl-4- (2-methylbenzyl) piperidine, N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]ethyl }-4-(2- methylbenzyl)isonipecotic acid methyl ester, N-{ [l-(4-Cyanobenzyl)-lH-imidazol-5-ylJmethyl } -trans-4-(3- methylphenyl)-3-hydroxypiperidine, N-{ [l -(4-Cyanobenzyl)-lH-imidazol-5-ylJmethyl } -trans-4- (3- methylphenyl)-3 methoxy piperidine, N-{ [l-(4-cyanobenzyl)-lH-imidazol-5-yl]methyl } -trans-4- (3- methylphenyl)-3 benzyloxy piperidine, l-[2(R,S)-Amino-3-(2-tetradecyloxyphenyl)ρropyl]-4~(2- methylbenzyl)isonipecotic acid methyl ester, N-2-(S)-aminolauroyl-4-(l-napthylmethyl) isonipecotic acid methyl ester, 4-(Benzoxazolidin-2-one-l-yl)-l-[l-(4-cyanobenzyl)-5- imidazolylacetyl]piperidine, 4-( 1 ,2-Dihydro-4(H)-3, 1 -benzoxazin-2-one- 1 -yl)- 1 -[ 1 -(4-cyanobenzyl)- 5-imidazolylacetyl]piperidine, 4-( 1 ,2-Dihydro-4(H)-3, 1 -benzoxazin-2-one- 1 -yl)- 1 -[1 -(4-cyanobenzyl)- 5-imidazolylmethyl]piperidine, N-[2- { (4-Cyanobenzyl)-5-imidazolyl }ethyl]-4-carbamoyl- 1 - phenylpiperidine hydrochloride or 4-[2-{ l-(4-Cyanobenzyl)-5-imidazolyl } ethyl]- 1 -phenylpiperidine hydrochloride 4-{5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine-l- ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethylbenzyI)-piperidine- 1 - ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethylbenzyl)-piperidine- 1 - ylmethyl]-2-methylimidazol-l -ylmethyl} benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(2-trifluoromethylbenzyl)-piperidine- l- ylmethyl]imidazol-l -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2-methylbenzyl)piperidine- 1 - ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine-l - ylmethyl]imidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine-l -ylmethyl]- 2-methylimidazol- 1 -ylmethyl }benzonitrile 4-(5- { 2-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine- 1 -yl]-2- oxoethy 1 } imidazol- 1 -ylmethyPbenzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-methylbenzyl)piperidine-l- carbonyl]imidazol- 1 -ylmethyl } benzonitrile 4- { 5- 14-Hydroxymethyl-4-(2-methylbenzyl)piperidine- 1 - carbonyl]imidazol-l -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3-chlorobenzyl)-piperidine- l -ylmethyl]- 2-methy limidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2-cyanobenzyl)-piperidine- 1 -ylmethylJ-2- mefhylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-cyanobenzyl)-piperidine- 1 -ylmethyl]-2- methylimidazol- 1 -ylmethyl }benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(4-cyanobenzyl)piperidine-l -ylmethyl]-2- methy limidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Hydroxymethyl-4-(2,5-dimethylbenzyl)piperidine-l- ylmethyl]-2-methylimidazol-l-ylmethyl }benzonitrile 4- { 5-[4-Hydroxymethyl-4-(2,5-dichlorobenzyl)piperidine- 1 - ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(3,5-dimethylbenzyl)piperidine-l- ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-(5-{4-Hydroxymethyl-4-[3,5-bis(trifluoromethyl)benzyl]- piperidine- 1 -ylmethyl } -2-methylimidazol- 1 -ylmethyPbenzonitrile 4- { 5-14-Hydroxymethyl-4-(2,3-dichlorobenzyl)piperidine- 1 - ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- [5 -(4-Hydroxymethy 1-4-benzylpiperidine- 1 -ylmethy l)-2- methylimidazol- 1 -ylmethyl]benzonitrile 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzamide 4-{ 5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine- 1 - ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-l-ylmethyl]- 2-methylimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine-l - ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Methoxymethy ] -4-(3-trifluoromethoxybenzyl)-piperidine- 1 ■ ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4- { 5-[4-Methoxymethyl-4-(2-trifluoromethoxybenzyl)-piperidine- 1 - ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-14-Methoxymethyl-4-(2-trifluoromethoxybenzyl)-piperidine- 1 - ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4- { 5-[4-Methoxymethyl-4-(3-cyanobenzyl)-piperidine- 1 -ylmethyl]-2- methy limidazol- 1 -ylmethyl } benzonitrile 4-(5- { 2-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine- 1 -yl]-2- oxoethyl } imidazol- 1 -ylmethyPbenzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-methylbenzyl)piperidine-l- carbonyl] imidazol- 1 -ylmethyl } benzonitrile Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4- (3-trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- cyanobenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-[3- (benzyloxycarbonylaminomethyl)benzyl]piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-[3- (aminomethyl)benzyl]piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-[3- (methanesulfonylaminomethyl)benzyl]piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-(3- nitrobenzyl)piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyl]-4-(3- methanesulfonylaminobenzyl)piperidine-4-carboxylate Ethyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- benzylpiperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4- cyclopropylmethylpiperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methylbenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methylbenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- trifluoromethoxybenzyl)piperidine-4-carboxylate Methyl 1 -[3-(4-cyanobenzyl)-3H-imidazol-4-ylacetyl ]-4-(3- cyanobenzyl)piperidine-4-carboxylate Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3- methylbenzyl)piperidine-4-carboxylate (±) Methyl 2-(n-butyl)-l-[3-(4-cyanobenzyl)-3H-imidazol-4- ylmethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- methy lbenzy l)isonipecotamide l-[3-(4-CyanobenzyI)-3H-imidazol-4-ylacetyl]-4-(3-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2-methyl- benzyl)isonipecotamide l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(4- methylbenzyl)piperidine-4-carbonitrile l-13-(4-Cyanobenzyl)-2-methyl-3H-imidazol-4-ylmethyll-4-(3- methylbenzyl)piperidine-4-carbonitrile 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylcarbonyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylacetyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3- methylbenzyl)piperidine-4-carbonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(2- methylbenzyl)piperidine-4-carbonitrile 4- { 5-[4-Hydroxymethyl-4-(4-methylpyridin-2-ylmethyl)-piperidine- l -ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4-{5-[4-Hydroxymethyl-4-(6-methylpyridin-2-ylmethyl)-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-{5-[4-Hydroxymethyl-4-(2-methylpyridin-4-ylmethyl)-piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyPbenzonitrile 4-{5-[4-Hydroxymethyl-4-(4-chloropyridin-2-ylmethyI)-piperidine- l-ylmethyl]-2-methylimidazol-l -ylmethyl } benzonitrile 4-{5-[4-Methoxymethyl-4-(6-methylpyridin-2-ylmethyl)-piperidine- 1 -ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Hydroxymethyl-4-(6-hydroxypyridin-2-ylmethyl)- piperidine- 1 -ylmethyl]-2-methylimidazol- 1 -ylmethyl } benzonitrile 4-[5-(4-Hydroxymethyl-4-quinolin-2-ylmethyl-piperidine-l- ylmethyl)-2-methylimidazol- 1 -ylmethyl]benzonitrile Methyl l-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzoyl)piperidine-4-carboxylate l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylbenzoyl)piperidine l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(hydroxy-m- tolylmethyl)piperidine 4- { 5-[4-Hydroxymethyl-4-(3-tolylsulfanyl)piperidine- 1 ylmethyllimidazol- 1 -ylmethyl } benzonitrile 4-{ 5-[4-Methoxymethyl-4-(3-tolylsulfanyl)piperidine-l- ylmethyllimidazol- 1 -ylmethyl }benzonitrile 4-{5-[4-Methoxymethyl-4-(3-tolylsulfinyl)piperidine-l- y lmethyl] imidazol- 1 -ylmethyPbenzonitrile 4-{5-[4-Methoxymethyl-4-(3-tolylsulfonyl)piperidine-l - ylmethyllimidazol- 1 -ylmethyl } benzonitrile l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)isonipecotamide Ethyl l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidine-4-carboxylate l -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-hydroxymethyl-4- (3-methylphenylamino)piperidine O- { 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methy lpheny lamino)piperidyl-4-methyl } carbamate 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylurea l-[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)piperidyl-4-methylsulfamide 4- { 5-[4-(Hydroxydiphenylmethyl)piperidin- 1 -ylmethyl]imidazol- 1 - ylmethyl } benzonitrile 4-{ 5-[4-(Hydroxydiphenylmethyl)piperidine-l-carbonyl]imidazol-] ylmethyl} benzonitrile 4-(5-{2-[4-(Hydroxydiphenylmethyl)ρiperidin- l-yl]-2-oxoethyl }-3H- imidazol- 1 -ylmethyPbenzonitrile l-(Piperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole 1 -( 1 -Phenylpiperidin-4-ylmethyl)-5-(4-cyanobenzyl)imidazole l-( 1 -(2-Methylphenyl)ρiperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole l-(l-(2-Chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 1 -( 1 -(3-Chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 1 -( 1 -(3-Chlorobenzenesulfonyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole l-(l-(3-Chlorobenzyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole 2-[3-(4-Cyanobenzyl)-3H-imidazol-l -yl]-N-( l -phenylpiperidin-4- yl)acetamide 2-[3-(4-Cyanobenzy I)-3H-imidazol- 1 -yl]-N-benzyl-N-( 1 - phenylpiperidin-4-yl)acetamide 2-[3-(4-Cyanobenzyl)-3H-imidazol- l -yl]-N-(l-phenylpiperidin-4-yl)- N-pyridin-4-ylmethylacetamide 2-[3-(4-Cyanobenzyl)-3H-imidazol-l-yl]-N-phenethyl-N-(l- phenylpiperidin-4-yl)acetamide 4- { 5- [( 1 -Phenylρiperidin-4-ylamino)methyl]imidazol- 1 - ylmethyl } benzonitrile 4-(5-{ [Benzyl(l-phenylpiperidin-4-yl)amino] methyl } imidazol- 1 - ylmethyl)benzonitrile 4-(5- { [( 1 -Phenylpiperidin-4-yl)pyridin-4- y lmethylamino]methyl } imidazol- 1 -ylmethyPbenzonitrile 4-(5- { [PhenethyK 1 -phenylpiperidin-4-y l)amino]methyl } imidazol- 1 - ylmethyPbenzonitrile 4- { 5- [2-( l-Phenylpiperidin-4-ylamino)ethyl]imidazol- 1 - ylmethyl } benzonitrile 4-(5-{2-[Benzyl(l-phenylpiperidin-4-yl)amino]ethyl} imidazol- 1- ylmethyl)benzonitrile 2-[3-(4-Cyanobenzyl)-3H-imidazol-l-yl]-N-(4-cyanobenzyl)-N-(l- phenylpiperidin-4-yl)acetamide N-(l-Benzylpiperidin-4-yl)-2-[3-(4-cyanobenzyl)-3H-imidazol-4- yl]acetamide and 4- { 5- [( 1 -Benzylpiperidin-4-y lamino)methyl]imidazol- 1 - ylmethyl } benzonitrile or a pharmaceutically acceptable salt or optical isomer thereof. 10. The compound according to Claim 9 which is: N- { [ 1 -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]methyl }-4-(3-methylphenyl)- 4-hydroxy piperidine or a pharmaceutically acceptable salt or optical isomer thereof. 1 1. The compound according to Claim 9 which is: 4- { 5-[4-Hydroxymethyl-4-(3-trifluoromethoxybenzyl)-piperidine- 1 • ylmethyllimidazol- 1 -ylmethyl } benzonitrile or a pharmaceutically acceptable salt or optical isomer thereof. 12. The compound according to Claim 9 which is: 4-{ 5-(4-Hydroxymethyl-4-(4-chloropyridin-2-ylmethyl)-piperidine- l ylmethyl]-2-methylimidazol- 1 -ylmethyl }benzonitrile or a pharmaceutically acceptable salt or optical isomer thereof. 13. The compound according to Claim 9 which is: 4- { 5-14-Methoxymethyl-4-(3-tolylsulfanyl)piperidine- 1 - ylmethyllimidazol- 1 -ylmethyl} benzonitrile trifluoroacetate salt or a pharmaceutically acceptable salt or optical isomer thereof. 14. The compound according to Claim 9 which is: 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl J-4-hydroxymethyl-4-(3- methylphenylamino)piperidine or a pharmaceutically acceptable salt or optical isomer thereof. 15. The compound according to Claim 9 which is: 1 -[3-(4-Cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3- methylphenylamino)-piperidyl-4-methylcarbamate or a pharmaceutically acceptable salt or optical isomer thereof. 16. The compound according to Claim 9 which is: 1 -( 1 -(3-Chlorobenzoyl)piperidin-4-ylmethyl)-5-(4- cyanobenzyl)imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 17. The compound according to Claim 9 which is: 4- { 5- [( 1 -Benzylpiperidin-4-ylamino)methyl]imidazol- 1 - ylmethyl } benzonitrile or a pharmaceutically acceptable salt or optical isomer thereof. 18. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 1. 19. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 2. 20. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 7. 21. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 8. 22. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 9. 23. A method for inhibiting farnesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 24. A method for inhibiting farnesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 19. 25. A method for inhibiting farnesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 20. 26. A method for inhibiting farnesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21. 27. A method for inhibiting farnesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 22. 28. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 29. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 19. 30. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 20. 31. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21. 32. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 22. 33. 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 14. 34. 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 14. 35. A method for treating infections from hepatitis delta and related viruses which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 14. 36. A method for preventing restenosis which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 14. 37. 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 14. 38. A pharmaceutical composition made by combining the compound of Claim 1 and a pharmaceutically acceptable carrier. 39. A process for making a pharmaceutical composition comprising combining a compound of Claim 1 and a pharmaceutically acceptable carrier. 34. 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 15. 35. 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 15. 36. A method for treating infections from hepatitis delta and related viruses which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 15. 37. A method for preventing restenosis which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 15. 38. 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 15.

Inventors: ANTHONY NEVILLE J, BELL IAN M, DINSMORE CHRISTOPHER, EMBREY MARK W, FISHER THORSTEN E, GOMEZ ROBERT P, HUTCHINSON JOHN H, WAI JOHN S, WILLIAMS THERESA M, ANTHONY, NEVILLE, J., BELL, IAN, M., DINSMORE, CHRISTOPHER, EMBREY, MARK, W., FISHER, THORSTEN, E., GOMEZ, ROBERT, P., HUTCHINSON, JOHN, H., WAI, JOHN, S., WILLIAMS, THERESA, M.
Applicants: ANTHONY NEVILLE J, BELL IAN M, DINSMORE CHRISTOPHER, EMBREY MARK W, FISHER THORSTEN E, GOMEZ ROBERT P, HUTCHINSON JOHN H, MERCK & CO INC, WAI JOHN S, WILLIAMS THERESA M, ANTHONY, NEVILLE, J., BELL, IAN, M., DINSMORE, CHRISTOPHER, EMBREY, MARK, W., FISHER, THORSTEN, E., GOMEZ, ROBERT, P., HUTCHINSON, JOHN, H., MERCK & CO., INC., WAI, JOHN, S., WILLIAMS, THERESA, M.
Application year: 1997
Main classification: A61K
IPC codes: A61K31, A61P9, A61P13, A61P27, A61P31, A61P35, A61P43, C07D211, C07D401, C07D413