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 a conformational change. The GTP- bound form of Ras propagates the growth stimulatory signal until the signal is terminated by the intrinsic GTPase activity of Ras, which returns the protein to its inactive GDP bound form (D.R. Lowy and D.M. Willumsen, Ann. Rev. Biochem. 62:851-891 (1993)). Mutated ras genes (Ha-rαs, Ki4a-rα^, Ki4b-rα_. and N-ras) are found in many human cancers, including colorectal carcinoma, exocrine pancreatic carcinoma, and myeloid leukemias. The protein products of these genes are defective in their GTPase activity and constitutively transmit a growth stimulatory signal. Ras must be localized to the plasma membrane for both normal and oncogenic functions. At least 3 post-translational modifications are involved with Ras membrane localization, and all 3 modifications occur at the C-terminus of Ras. The Ras C-terminus contains a sequence motif termed a "CAAX" or "Cys-Aaa^-Aaa^-Xaa" box (Cys is cysteine, Aaa is an aliphatic amino acid, the Xaa is any amino acid) (Willumsen et al., Nature J/0.583-586 (1984)). Depend¬ ing on the specific sequence, this motif serves as a signal sequence for the enzymes famesyl-protein transferase or geranylgeranyl-protein transferase, which catalyze the alkylation of the cysteine residue of the CAAX motif with a C15 or C20 isoprenoid, respectively. (S. Clarke., Ann. Rev. Biochem. 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 famesyl- ation. Other famesylated proteins include the Ras-related GTP-binding proteins such as Rho, fungal mating factors, the nuclear lamins, and the gamma subunit of transducin. James, et al., J. Biol. Chem. 269, 14182 (1994) have identified a peroxisome associated protein Pxf which is also famesylated. James, et al., have also suggested that there are famesyl¬ ated proteins of unknown stmcture and function in addition to those listed above. Inhibition of famesyl-protein transferase has been shown to block the growth of Ras-transformed cells in soft agar and to modify other aspects of their transformed phenotype. It has also been demonstrated that certain inhibitors of famesyl-protein transferase selectively block the processing of the Ras oncoprotein intracellularly (N.E. Kohl et ai, Science, 260: 1934-1937 (1993) and G.L. James et al., Science, 260:1937-1942 (1993). Recently, it has been shown that an inhibitor of famesyl-protein transferase blocks the growth of ras- dependent tumors in nude mice (N.E. Kohl et al., Proc. Natl. Acad. Sci U.S.A., 97 :9141 -9145 (1994) and induces regression of mammary and salivary carcinomas in ras transgenic mice (N.E. Kohl et al., Nature Medicine, 1 :792-797 (1995). Indirect inhibition of famesyl-protein transferase in vivo has been demonstrated with lovastatin (Merck & Co., Rahway, NJ) and compactin (Hancock et al., ibid; Casey et al., ibid; Schafer et al., Science 245:379 (1989)). These drugs inhibit HMG-CoA reductase, the rate limiting enzyme for the production of polyisoprenoids includ- ing famesyl pyrophosphate. Famesyl-protein transferase utilizes famesyl pyrophosphate to covalently modify the Cys thiol group of the Ras CAAX box with a famesyl group (Reiss et al., Cell, 62:81 -88 (1990); Schaber et al. , J. Biol. Chem., 265:14701-14704 (1990); Schafer et al.. Science, 249: \ 133-1 139 (1990); Manne et al., Proc. Natl. Acad. Sci USA , 87:75 1 -7545 (1990)). Inhibition of famesyl pyrophosphate biosynthesis by inhibiting HMG-CoA reductase blocks Ras membrane localization in cultured cells. However, direct inhibition of famesyl- protein transferase would be more specific and attended by fewer side effects than would occur with the required dose of a general inhibitor of isoprene biosynthesis. Inhibitors of famesyl-protein transferase (FPTase) have been described in four general classes (S. Graham, Expert Opinion Ther. Patents, (1995) 5:1269-1285). The first are analogs of famesyl diphosphate (FPP), while a second class of inhibitors is related to the protein substrates (e.g., Ras) for the enzyme. Bisubstrate inhibitors and inhibitors of famesyl-protein transferase that are non-competitive with the substrates have also been described. The peptide derived inhibitors that have been described are generally cysteine containing molecules that are related to the CAAX motif that is the signal for protein prenylation. (Schaber et al., ibid; Reiss et. al., ibid; Reiss et al., PNAS, 88:732-736 (1991)). Such inhibitors may inhibit protein prenylation while serving as alternate substrates for the famesyl-protein transferase enzyme, or may be purely competitive inhibitors (U.S. Patent 5,141,851 , University of Texas; N.E. Kohl et al, Science, 260: 1934-1937 (1993); Graham, et al., J. Med. Chem., 37, 725 (1994)). In general, deletion of the thiol from a CAAX derivative has been shown to dramatically reduce the inhibitory potency of the compound. However, the thiol group potentially places limitations on the therapeutic application of FPTase inhibitors with respect to pharmacokinetics, pharmacodynamics and toxicity. Therefore, a functional replacement for the thiol is desirable. It has recently been disclosed that certain tricyclic compounds which optionally incorporate a piperidine moiety are inhibitors of FPTase (WO 95/10514, WO 95/10515 and WO 95/10516). Imidazole-containing inhibitors of famesyl protein transferase have also been disclosed (WO 95/09001 and EP 0 675 1 12 Al ). It has recently been reported that famesyl-protein transferase inhibitors are inhibitors of proliferation of vascular smooth muscle cells and are therefore useful in the prevention and therapy of arteriosclerosis and diabetic disturbance of blood vessels (JP H7- 1 12930). It is, therefore, an object of this invention to develop low molecular weight compounds that will inhibit famesyl-protein transferase and thus, the post-translational famesylation of proteins. It is a further object of this invention to develop chemotherapeutic compositions containing the compounds of this invention and methods for producing the compounds of this invention. SUMMARY OF THE INVENTION The present invention comprises novel biaryl-containing compounds which inhibit the famesyl-protein transferase. Further contained in this invention are chemotherapeutic compositions containing these famesyl transferase inhibitors and methods for their production. The compounds of this invention are illustrated by the formula A: DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention are useful in the inhibition of famesyl-protein transferase and the famesylation of the oncogene protein Ras. In a first embodiment of this invention, the inhibitors of famesyl-protein transferase are illustrated by the formula A: wherein: Rla and Rl° are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, Rl lS(0) m -, R10C(0)NR10_, Rl lC(0)0-, (Rl0)2NC(O)-, R10 2 N-C(NR10)-, CN, Nθ2, RlOC(O)-, N3,-N(RlO)2,orRllOC(0)NRlO-, c) unsubstituted or substituted C l -Co alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, RllS(O) m -,Rl0C(O)NRl0-,(Rl0) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(Rl ) 2 , and RllOC(O)-NRl0-; R-, R3, R4 and R^ are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0) m -, RlOC(0)NRlO-, (Rl0) 2 NC(O)-, Rl lC(0)0-, Rl0 2 N-C(NRlO)-, CN, N02, R 10 C(O)-, N3, -N(RlO) 2 , orRHOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl -Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 12θ-, R 1 1 S(0) m -, R 10C(O)NR 10-, (R 10) 2 NC(O)-, R 10 2N _C(NR 10)-, CN, RlOC(O)-, N3, -N(R lO) 2 , and R l lOC(O)-NR l0-; R 6a , R 6b , R 6c , R 6d and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl -Cό perfluoroalkyl, Rl 2 0-, Rl lS(0) m -, R10C(O)NR10-, (RlO) 2 NC(0)-, R H C(0)0-, Rl0 2 N-C(NRlO)-, CN, N02, R 10 C(O)-, N3, -N(RlO)2, or RHOC(O)NRl0-, c) unsubstituted C 1 -Co alkyl , d) substituted Cl -Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 12 0 -, Rl lS(0) m -, R 1 l S(O) m NRl0-, (R l°)2NS(0) m -. Rl 3c(O)NR l0-, (RlO)2NC(0)-, R102N-C(NR 10)-, CN, R lOC(O)-, N3, -N(RlO)2, and Rl 10C(0)-NR 10- ; any two of R oa , R^b. R6C ? Rod a nd R oe on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R3, R4, R , Rόa, Rob, R6C ? Rod or Rόe is unsubstituted or substituted heterocycle, attachment of R2, R3, R4 ? R5 ? Rόa, Rob, R 6c , R όd or R 6e t0 the phenyl ring is through a substitutable heterocycle ring carbon; R 7 is selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl -4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, h) Cl -4 perfluoroalkyl; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycleC3-Clθ cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, R lOO-, R l ^(OJm-, R !0C(O)NR 10-, (RlO)2NC(0)-, Rl 2 N-C(NRlO)-, CN, Nθ2, R 1°C(0)-, N3, -N(R ] 0)2, or R 1 1 OC(0)NR 10-, and c) Cl-Cό alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, R IOO-, R 1 1 S(0) m -, R ! 0C(O)NH-, (R 1 ) 2 NC(O)-, R l0 2 N-C(NR lO)-, CN, R l Oc(O)-, N3, -N(R l O) 2 , or Rl0θC(O)NH-; provided that when R8 is heterocycle, attachment of R to V is through a substitutable ring carbon; R9 is independently selected from: a) hydrogen. b) C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, halogen Rl lO-, Rl lS(0) m - . R 10 C(O)NRl0-, (Rl0)2NC(O)-, Rl°2N-C(NRlO)-, CN, N02, Rl°C(0)-, N3, -N(Rl )2, or Rl lOC(O)NRl0-, and c) C 1 -Co alkyl unsubstituted or substituted by C l -Co perfluoroalkyl, F, Cl, Br, Rl O-, RHS(0) m -, R!0C(O)NR10_, (Rl0) 2 NC(O)-, Rl0 2 N-C(NRl )_, CN, Rl C(O)-, N3, -N(Rl ) 2) or Rl 10C(0)NR10- ; Rl is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, C1-C6 substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl3 is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(RlO)2, benzyl and aryl; Al and A 2 are independently selected from: a bond, -CH=CH-, -C--C-, -C(O)-, -C(O)NRl0-, -NR10C(O)-, O, -N(R10)_, -S(O)2N(Rl0)-, -N(Rl0)S(O)2- or S(0) m ; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a 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 is a bond, n is 0 and A 2 is S(0)m . provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; W is a heterocycle; X is a bond, -CH=CH-, O, -C(=0)-, -C(0)NR7-, -NR7C(0)-, -C(0)0-, -OC(O)-, -C(0)NR7C(0)-, -S(0)2N(Rl )_, -N(Rl0)S(O)2- or -S(=0)m-; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; p is independently 0, 1, 2, 3 or 4; q is 0, 1, 2 or 3; r is 0 to 5, provided that r is 0 when V is hydrogen; and t is 0 or 1 ; or the pharmaceutically acceptable salts thereof. A preferred embodiment of the compounds of this invention is illustrated by the following formula: V - A 1 (CR 1a 2 ) n A 2 (CR 1a 2 ) n V W / (CR 1D 2 ) p - X wherein: Rla is independently selected from: hydrogen, C3-C10 cycloalkyl, R10 O _, -N(RlO)2, F or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, Rl O-, -N(R 10 )2, F or C2-C6 alkenyl, c) unsubstituted or substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, R^O- and -N(RlO) 2 ; R 2 , R3, R4 and R^ are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R! C(O)NR10-, (Rl ) 2 NC(0)-, Rl0 N-C(NRlO)-, CN, N02, R 10 C(O)-, N3, -N(RlO) 2 , OΓ RHOC(O)NR10-, c) unsubstituted Cl-Cό alkyl; d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR10-, (RlO) 2 NC(0)-, Rl 2N-C(NRl )-, CN, RIO O)-, N3, -N(Rl ) 2 , and R11OC(O)-NR10-; R°A R6b ? ROC 5 Rod an d R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0) m -, Rl C(0)NRlO-, (RlO) 2 NC(0)-, R10 2 N-C(NR10)-, CN, N02, R 10 C(O)-, N3, -N(RlO) , orRHOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl; d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 2θ-, Rl lS(0)m-, Rl lS(O) m NRl0-, (Rl°)2NS(0) m -, R13C(O)NR10-, (Rl0) 2 NC(O)-, R10 2 N-C(NR1°)-, CN, Rl C(O)-, N3, -N(Rl )2, and Rl 10C(0)-NR10- ; any two of R°\ R6b ^ R6C ? Rod a nd R^e 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R3, R4. R5, Rόa, ROb ? ROC, Rod or R6e is unsubstituted or substituted heterocycle, attachment of R 2 , R 3 , R 4 , R 5 , R 6a , R 6b , R 6c , R 6d or R°e t0 the phenyl ring is through a substitutable heterocycle ring carbon; R7 is selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, ,11 o f) — S0 2 R 11 g) N(RlO )2 or h) Cl-4 perfluoroalkyl; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, Cl-Cό alkyl, C2-Cό alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, R10(3-, R10C(O)NR10-, CN, Nθ2, (R1°)2N-C(NR10)_, Rl C(O)-, -N(Rl0) 2 ,orRllOC(O)NRl0-, and c) C l -Co alkyl substituted by C l -Co perfluoroalkyl , R 1 °0- , Rl0C(O)NRl0-, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(Rl )2, or Rl lOC(O)NRl0-; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9 is independently selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, Rl lO-, Rl lS(0) m -, R!0C(O)NR1 -, (RlO) 2 NC(0)-, CN, Nθ2, (Rl°)2N-C(NRl0)-, RlOC(O)-, -N(R!0) 2 , or RllOC(O)NRl0-, and c) C 1 -Co alkyl unsubstituted or substituted by C 1 -Co perfluoroalkyl, F, Cl, RlOO-, R 1 lS(0) m -, R!0C(O)NR10_, (Rl0) 2 NC(O)-, CN, (Rl )2N-C(NRl )_, RIOC(O)-, -N(R 10)2, or R 11 OC(0)NR 10- ; RI is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; R 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, C1-C6 substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl i s independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(R O) 2 , benzyl and aryl; Al and A 2 are independently selected from: a bond, -CH=CH-, -CHC-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl and thienyl, c) aryl, d) Cl-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 2 is S(0) m ; provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; W is a heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, triazolyl or isoquinolinyl; X is a bond, O, -C(=0)-, -CH=CH-, -C(0)NR7-, -NR7C(0)-, -S(0)2N(RlO)_, -N(Rl O)S(0)2- or -S(=0) m -; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; q is 0, 1, 2 or 3; p is independently 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; and t is 0 or 1 ; or the pharmaceutically acceptable salts thereof. A preferred embodiment of the compounds of this invention are illustrated by the formula B: wherein: Rl is independently selected from: hydrogen, C3-C10 cycloalkyl, RlOO-, -N(RlO) 2 , F or C l -Cό alkyl; R l b is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C 10 cycloalkyl, Rl°0-, -N(RlO)2, F or C2-C6 alkenyl, c) unsubstituted or substituted Cl -Cό alkyl wherein the substituent on the substituted C l -Co alkyl is selected from unsubstituted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, R l O- and -N(R lO) 2; R 2 and R 3 are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 5 - alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR1 -, (R10) 2 NC(O R10 2 N-C(NR10)-, CN, N02, R 10 C(O)-, N3, -N ( RlO)2, orRllθC(O)NRl0_, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R J2 0-, Rl lS(0)m-, R!0C(O)NR10-, (RlO) 2 NC(0)-, Rlθ2N-C(NRlO)-, CN, Rl c(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10_ ; Rόa ^ R6b 9 R6C ? Rod and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R12O-, RllS(0) m -, Rl0c(O)NRl0-, (Rl0) 2 NC(O)-, Rlθ2N-C(NRl° CN, Nθ2, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-Cό alkenyl, C2-C6 alkynyl, Rl 0-, Rl lS(0)m-, R π S(O) m NRl0-, (R 10 )2NS(O) m -, Rl3C(O)NRl0-, (RlO) 2 NC(0)-, R10 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(Rl0)2, and Rl 1QC(O)-NR10- ; any two of R°Λ R6b 5 R6C ; Rod anc j Rόe on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R3, R6a, R6b ; ROC, Rod or R6e j s unsubstituted or substituted heterocycle, attachment of R 2 , R3, R6a, R6b, R6C, Rod or R6e t0 the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl -Cό perfluoroalkyl, F, Cl, Rl O-, Rl0c(O)NRl0-, CN, NO2, (R 10 )2N-C(NR lO)-, Rl c(O)-, -N(RlO)2, or R l 10C(0)NR 10-, and c) Cl -Cό alkyl substituted by Cl -Cό perfluoroalkyl, Rl°0-, Rl°C(O)NR l0-, (R !0) 2 N-C(NR10)_, R 10C(O)-, -N(Rl )2, or Rl lOC(O)NRl - ; provided that when R8 is heterocycle, attachment of R^ to V is through a substitutable ring carbon; R9a and R^b are independently hydrogen, Cl -Cό alkyl, trifluoromethyl and halogen; R lO is independently selected from hydrogen, Cl -Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl -Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl -Cό alkyl, Cl -Cό aralkyl, -C6 substituted aralkyl, Cl -Cό heteroaralkyl, C l -Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl -Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; R l3 is independently selected from hydrogen, Cl -Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(Rl )2, benzyl and aryl; A! and A 2 are independently selected from: a bond, -CH=CH-, -C=C-, -C(O)-, -C(O)NRl0-, -NRlOC(O)-, O, -N(RlO)_, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl and thienyl, c) aryl, d) Cl-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A 2 is S(0)m . provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; X is a bond, -CH=CH-, -C(O)NRl0-, -NRIOC(O)-, O or -C(=0)-; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; and r is 0 to 5, provided that r is 0 when V is hydrogen; or the pharmaceutically acceptable salts thereof. Another preferred embodiment of the compounds of this invention are illustrated by the formula C: .8 wherein: R la is independently selected from: hydrogen, C3-C10 cycloalkyl, R lOO-, -N(RlO)2, F or C l-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3- 0 cycloalkyl, Rl°0-, -N(R lO)2, F or C2-C6 alkenyl, c) unsubstituted or substituted Cl-Cό alkyl wherein the substituent on the substituted C l -Co alkyl is selected from unsubstituted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, R l O- and -N(R*0)2; R 2 and R3 are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R 10 C(O)NRl0-, CN(Rl0) 2 NC(O)-, R l0 N-C(NR lO)-, CN, Nθ2, R 10 C(O)-, N3, -N(R l°)2, or R l lOC(O)NR l0-, c) unsubstituted C l -Co alkyl , d) substituted Cl -Cό alkyl wherein the substituent on the substituted Cl -Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, RllS(0) m -, R!0C(O)NR10-, (RlO) 2 NC(0)-, R10 2 N_C(NR1 )-, CN, Rl C(O)-, N3, -N(RlO) 2 , and RHOC(O)-NR10-; Roa, R6b ? R6C 5 Rod an d R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C 1 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl !S(0)m-, R!0C(O)NR10-, CN(RlO) 2 NC(0)-, Rl0 2 N-C(NRl )-,CN,Nθ2, Rl°C(0)-, N3, -N(RlO)2, orRHOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0) m -, Rl lS(O) m NRl0-, (RlO) 2 NS(0) m -, R!3C(O)NR10_, (Rl0) 2 NC(O)-, R!0 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(Rl )2, and RHOC(O)-NR10-; any two of R°A R6b 5 R6 C Rod a nd R^e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R3, R6a, Rόb, ROC, Rod or R e j s unsubstituted or substituted heterocycle, attachment of R 2 , R3, R6a, R6b ? R 6c, R 6d or Rόe t0 the pheny j ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, Cl-Cό alkyl, C2-Cό alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, RlOO-, Rl0c(O)NRl0-, CN, N02, (R 10 )2N-C(NRlO)., R 1 0 C(O)-, -N(R 10)2, or R 11 OC(0)NR 10., and c) Cl-Cό alkyl substituted by Cl-Cό perfluoroalkyl, RlOO-, Rl0C(O)NRl0-, (R!0) 2 N-C(NR10)_, RlOc(O)-, -N(Rl0)2, or Rl lOC(O)NRl0- ; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R^a and R^b are independently hydrogen, Cl-Cό alkyl, trifluoromethyl and halogen; RlO is independently selected from hydrogen, Cl-C6 alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, C]-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl3 is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(Rl0)2, benzyl and aryl; Al and A 2 are independently selected from: a bond, -CH=CH-, -C≡C- -C(O)-, -C(O)NRl0-, O, -N(R10)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl and thienyl, 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, and provided that V is not hydrogen if A is S(0) and V is not hydrogen if A is a bond, n is 0 and A 2 is S(0)m. provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; X is a bond, -CH=CH-, -C(O)NRl0-, -NRIO O)-, O or -C(=0)-; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; p is 0, 1 , 2, 3 or 4, provided that p is not 0 if X is a bond, -NR10C(O)-, -NRlO- or O; and r is 0 to 5, provided that r is 0 when V is hydrogen; or the pharmaceutically acceptable salts thereof. In a more preferred embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula D: wherein: Rla is independently selected from: hydrogen, C3-C10 cycloalkyl or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -N(R10)2, F or C2-C6 alkenyl, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3- 0 cycloalkyl, C2-C6 alkenyl, R 10 O-. or -N(RlO) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, Rl°C(O)NRl0-, (RlO) 2 NC(0)-, Rl0 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3,-N(RlO)2, orRllOC(O)NRl0-, c) unsubstituted C l -Co alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, RllS(0)m-, R 10 C(O)NRl0-, (Rl0) 2 NC(O)-, R!0 2 N-C(NR10)-, CN, RlOc(O)-, N3, -N(RlO) 2 , and R110C(0)-NR1°-; R3 is selected from H, halogen, Cl-Cό alkyl and CF3; R6a, R6b ; R6C 5 Rod an d R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, RllS(0) m -, R10C(O)NR10-, (R10) 2 NC(O)-, Rl0 N-C(NRl )-, CN, N02, Rl°C(0)-, N3, -N(Rl ) 2 , orRllθC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, Rl°C(O)NRl0-, (R10) 2 NC(O)-, Rl°2N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and R110C(0)-NR1°-; any two of R°Λ R6b ? R6C } od anf R6e 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3 provided that when R 2 , R°a, R6b, R6C, Rod or R6e j s unsubstituted or substituted heterocycle, attachment of R 2 , R6a s Rόb. R6C ? Rod or R6e t0 the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, RIOO, R10C(O)NR10-, CN, Nθ2, (R1°)2N-C(NR10)-, Rl°C(0)-, -N(Rl0) 2 ,orRllθC(O)NRl0-, and c) C l -Co alkyl substituted by C 1 -Co perfluoroalkyl, R 1 °0-, Rl0c(O)NRl0-, (RlO) 2 N-C(NRlO)_, RlOc(O)-, -N(RlO)2, or Rl lOC(O)NRl0-; or provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9 and R^ are independently hydrogen, halogen, CF3 or methyl; R O is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; A 1 is selected from: a bond, -C(O)-, O, -N(R10)_, 0 r S(0) m ; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)-; n is 0 or 1 ; provided that n is not 0 if A is a bond, O, -N(RlO)-, or S(0) m ; m is 0, 1 or 2; and p is 0, 1, 2, 3 or 4; or the pharmaceutically acceptable salts thereof. In another more preferred embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula E: wherein: Rla is independently selected from: hydrogen, Rl O-, -N(RlO)2, F, C3-C10 cycloalkyl or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3- 0 cycloalkyl, RlOO-, -N(RlO)2, F or C2-C6 alkenyl, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO-, or -N(RlO) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 perfluoroalkyl, Rl 2 0-, RllS(0) m -, Rl0c(O)NRl0-, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstituted C 1 -Co alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R12O-, Rl lS(0)m-, R!0C(O)NR10-, (Rl0) 2 NC(O)-, Rlθ2N-C(NRlO)-, CN, RlOc(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0- ; R3 is selected from H, halogen, Cl-Cό alkyl and CF3; R6a, R6b. R6C, Rod an d Roe are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R12O-, Rl lS(0) m -, Rl0c(O)NRl0-, (Rl0) 2 NC(O)-, Rlθ2N-C(NRlO)-, CN, N02, Rl°C(0)-, N3,-N(Rl0)2, orRl θC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, RHS(O)m-,Rl0C(O)NRl0-, (Rl0) 2 NC(O)-, Rlθ2N-C(NRlO)-, CN, Rl C(O)-, N3, -N(RlO) , and RllOC(O)-NRl0-;or any two of R^a. R6b 5 6C ? Rod a nd R6e 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R6a. R6b, R6C ? Rod or Roe i s unsubstituted or substituted heterocycle, attachment of R 2 , R 6a , R 6b , R6c, Rod or Roe to the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl -Cό perfluoroalkyl, F, Cl, R OO-, R10C(O)NR10-, CN, N02, (RlO) 2 N-C(NR O)-, RlOc(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) C l -Co alkyl substituted by C l -Co perfluoroalkyl, R OO-, RlOC(0)NRlO-, (RlO) 2 N-C(NRlO)-, RlOc(O)-, -N(Rl0)2, or Rl lOC(O)NRl0- ; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9 and R9 are independently hydrogen, halogen, CF3 or methyl; RlO i independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl -Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)-; n is 0 or 1 ; m is 0, 1 or 2; and p is 0, 1, 2, 3 or 4, provided that p is not 0 if X is a bond or O; or the pharmaceutically acceptable salts thereof. In a further embodiment of this invention, the inhibitors of famesyl-protein transferase are illustrated by the formula F: wherein: R la is independently selected from: hydrogen, C3-C10 cycloalkyl or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3- 0 cycloalkyl, Rl°0-, -N(R10)2 or F, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, Rl OO-, or -N(RlO) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl -Cό perfluoroalkyl, R 12O-, Rl l S(0) m -, RlOC(0)NR lO-, (R lO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, Nθ2, R 10 C(O)-, N3, -N(R lO) 2 , or Rl lOC(O)NR l0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl -Cό alkyl wherein the substituent on the substituted Cl -Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 1 2 0-, R 1 1 S(0)m-, R l °C(0)NR 10 . , (R 10) 2 NC(O)-, R l0 2 N-C(NR lO)-, CN, R lOC(O)-, N3, -N(RlO) 2 , and R l lOC(O)-NR l0- ; R3 is selected from H, halogen, CH3 and CF3; ROa 5 R6b 5 R6C ? Rod an d R6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-Cό alkynyl, halogen, Cl -Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R 10 C(O)NRl _, (Rl0) 2 NC(O)-, R l0 2 N-C(NRlO)-, CN, N02, R 10 C(O)-, N3, -N(RlO) 2 , or R HOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted C l -Co alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 0-, R l lS(0) m -, R 1°C(0)NR 10-, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, R lOC(O)-, N3, -N(RlO) , and Rl lOC(O)-NR l0-; or any two of R^ . R6b ? R6C ? Rod anf j Rόe 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3 provided that when R 2 , R6 , R6b R6C, Rod or R6e j s unsubstituted or substituted heterocycle, attachment of R 2 , R6a, R6b ? R6C ? Rod or Rόe t0 the phenyl ring is through a substitutable heterocycle ring carbon; R and R9b are independently hydrogen, halogen, CF3 or methyl; R O is independently selected from hydrogen, Cl-Cό alkyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)-; m is 0, 1 or 2; and p is 0, 1, 2, 3 or 4; or the pharmaceutically acceptable salts thereof. In a further embodiment of this invention, the inhibitors of farnesyl-protein transferase are illustrated by the formula G: wherein: Rla is independently selected from: hydrogen, RlOO-, -N(R l )2, F, C3-C10 cycloalkyl or Cl -Cό alkyl; R ib is independently selected from: a) hydrogen, b) aryl, heterocycle or C3-C10 cycloalkyl, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, R l°0-, or -N(RlO) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 12 ( 3-, Rl lS(0)m-, R 10 C(O)NR l0.. (Rl0) 2 NC(O)-, R 10 2 N-C(NR10)-, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , or RHOC(0)NRlO-, c) unsubstituted Cl-Cό alkyl, d) substituted C1-C6 alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 12O-, Rl lS(0)m-, R 10 C(O)NRl0-, (RlO) 2 NC(0)-, R l0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(R lO) 2 , and Rl lOC(O)-NRl0- ; R is selected from H, halogen, CH3 and CF3; R6a, R6b ? 6C, Rod an d R6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 1 2 0-, R 11 S(0) m - . R l °C(0)NR 10-, (R 10) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN,N02, R 10 C(O)-, N3, -N(RlO)2, orRllθC(O)NRl0_, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR10_, (R10) 2 NC(O)-, Rl°2N-C(NRlO)-, CN, RlOc(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0- ; or any two of R^a, R6b ? R6C ? Rod a nd R^ on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R°\ R6b, ROC, Rod or Roe j s unsubstituted or substituted heterocycle, attachment of R 2 , R 6a , R 6b , Roc, Rod or Roe t0 the phenyl ring is through a substitutable heterocycle ring carbon; R9a and R b are independently hydrogen, halogen, CF3 or methyl; Rl is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Al is selected from: a bond, -C(O)-, O, -N(R 10)_, or S(0) m ; m is 0, 1 or 2; and n is 0 or 1 ; or the pharmaceutically acceptable salts thereof. The preferred compounds of this invention are as follows: l -(4-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole l -(4-Cyanobenzyl)-5-(4'-phenylbenzamido)ethyl-imidazole l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole 1 -(4-Biphenylethyl)-5-(4-cyanobenzyl)imidazole l -(2'-Bromo-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole 1 -(2'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(3',5'-dichloro)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-Methoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(3-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(3',5'-Bis-trifluoromethyl)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)-4- methylimidazole l -(4-Biphenylmethyl)-5-(4-cyanophenyloxy)-imidazole 5-(4-Cyanophenyloxy)- 1 -(2'-methyl-4-biphenylmethyl)-imidazole 5-(4-Biphenyloxy)- 1 -(4-cyanobenzy l)-imidazole 5-(2'-Methyl-4-biphenoxy)- 1 -(4-cyanobenzyl)-imidazole 5-(4-(3',5'-dichloro)biphenylmethyl)-l-(4-cyanobenzyl)imidazole 1 -(4-biphenylmethyl)-5-( 1 -(R,S)-acetoxy- 1 -(4- cyanophenyl)methylimidazole 1 -(4-Biphenylmethyl)-5-( 1 -(R,S)-hydroxy- 1 -(4-cyanophenyl) methylimidazole 1 -(4-Biρhenylmethyl)-5-( 1 -(R,S)-amino- 1 -(4-cyanophenyl) methylimidazole 1 -(4-biphenylmethyl)-5-( 1 -(R,S)-methoxy- 1 -(4-cyanophenyl)- methylimidazole 1 -(4-Cyanobenzyl)-5-( 1 -hydroxy- 1 -(4-biphenyI)-methyl) imidazole 1 -(4-Cyanobenzyl)-5-(l -oxo- 1 -(4-biphenyl)-methyl) imidazole 1 -(4-Cyanobenzyl)-5-( 1 -hydroxy- 1 -(3-fluoro-4-biphenyl)-methyl)- imidazole 1 -(4-Cyanobenzyl)-5-( 1 -hydroxy- 1 -(3-bipheny l)methyl-imidazole 5-(2-[ 1 , 1 '-Biphenyljviny lene)- 1 -(4-cyanobenzyl)imidazole l -(4-Biphenylmethyl)-5-(4-bromophenyloxy)-imidazole l -(3'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(4'-Methyl-4-biphenylmethy l)-5-(4-cyanobenzy 1) imidazole l -(3'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(4'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(3'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(4'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'3'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'4'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'5'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(3'-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-Fluoro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(2'-Trifluoromethylphenyl)-2-Chlorophenylmethyl)-5-(4- cyanobenzyl) imidazole 1 - { 1 -(4-(2'-trifluoromethylpheny l)phenyl)ethyl } -5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethyl-4-biphenylpropyl)-5-(4-cyanobenzyl) imidazole l -(2'-N-t-Butoxycarbonylamino-4-biphenylmethyl)-5-(4- cyanobenzyl) imidazole 1 -(2'-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Acetylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Methylsulfonylaminomethyl-4-biphenylmethyl)-5-(4- cyanobenzyl) imidazole l -(2'-Ethylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Phenylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Glycinylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2 ' -Methyl-4-biphenylmethyl)-2-chloro-5-(4-cyanobenzyl) imidazole l -(2'-Methyl-4-biphenylmethyl)- 4-chloro 5-(4-cyanobenzyl) imidazole l -(3'-Chloro-2-methyl-4-biphenylmethyl)-4-(4- cyanobenzyl)imidazole l -(3'-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-4-(4- cyanobenzyl) imidazole l -(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3'-Methoxy-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(2'-Chloro-4'-fluoro-4-biphenylmethyl)-5-(4- cyanobenzy 1 )imidazole l -(2'-Ethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole l -(2'-(2-Propyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole l -(2'-(2-Methyl-2-propyl)-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(2'-Ethyl-4-biphenylmethyl)-5-(4-(l//-tetrazol-5- yl))benzyl)imidazole l -[ l-(4-Cyanobenzyl)imidazol-5-ylmethoxy]-4-(2'-methylphenyl)-2- (3-N-phthalimido- 1 -propy l)benzene l -(3',5'-Ditrifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3 * ,5'-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3',5'-Dimethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3-(N-Boc-aminomethyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)- imidazole l -(3-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole 1 -(4-Cyanobenzyl)-2-methyl-5-(2'-methylbiphenyl-4- yloxy)imidazole 5-(4-Cyanobenzyl)-l -(3-cyano-2'-trifluoromethylbiphenyl-4-ylmethyl)- imidazole 2-Amino-5-(biphenyl-4-ylmethyl)- 1 -(4-cyanobenzyl)imidazole 2- Amino- 1 -(biphenyl-4-ylmethyl)-5-(4-cyanobenzyl)imidazole l -(3-Butylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole l -(3-Propylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole l-(4-Biphenylmethyl)-4-(4-cyanobenzyl-2-methylimidazole 1 -(4-Cyanobenzyl)-5-[(3-fluoro-4-biphenyl)methylJimidazole 1 -(4-Cyanobenzyl)-5-[ 1 -(4-biphenyl)- 1 -hydroxy]ethyl-2- methylimidazole l-(4-Cyanobenzyl)-5-(4-biphenylmethyl)-2-methylimidazole l -(4-Cyanobenzyl)-5-[l -(4-biphenyl)]ethyl-2-methyl imidazole l-(4-Cyanobenzyl-5-[ l -(4-biphenyl)]vinylidene-2-methylimidazole and l -(4-Cyanobenzyl)-5- 2-(4-biphenyl)]vinylene-2-methylimidazole or the pharmaceutically acceptable salts or optical isomers thereof. Specific examples of the compounds of the invention are: l -(4-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole 1 -(2'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole -(2'-Methoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(3',5'-dichloro)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 5-(2'-Methyl-4-biphenoxy)- 1 -(4-cyanobenzyl)-imidazole 1 -(4-Cyanobenzyl)-5-( 1 -hydroxy- 1 -(3-fluoro-4-biphenyl)-methyl)- imidazole 1 -(4'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2',5'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(3'-Methoxy-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole 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, R l a , Rib 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" and the alkyl portion of aralkyl and similar terms, 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. As used herein, "cycloalkyl" is intended to include non- aromatic cyclic hydrocarbon groups having the specified number of carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. "Alkenyl" groups include those groups having the specified number of carbon atoms and having one or several double bonds. Examples of alkenyl groups include vinyl, allyl, isopropenyl, pentenyl, hexenyl, heptenyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, 1-propenyl, 2-butenyl, 2-methyl-2-butenyl, isoprenyl, famesyl, geranyl, geranylgeranyl and the like. "Alkynyl" groups include those groups having the specified number of carbon atoms and having one triple bonds. Examples of alkynyl groups include acetylene, 2-butynyl, 2-pentynyl, 3-pentynyl and the like. "Halogen" or "halo" as used herein means fluoro, chloro, bromo and iodo. As used herein, "aryl," and the aryl portion of aralkyl and aroyl, 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, tetrahydro- naphthyl, 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 hetero¬ cyclic rings is fused to a benzene ring. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable stmcture. Examples of such heterocyclic elements include, but are not limited to, azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, phthalimid-1 -yl, 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 R7, the substituted Cl _8 alkyl, substituted C3-6 cycloalkyl, substituted aroyl, substituted aryl, substituted heteroaroyl, substituted arylsulfonyl, substituted heteroaryl¬ sulfonyl and substituted heterocycle include moieties containing from 1 to 3 substituents 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 -Cό alkyl)2, N02, CN, (Cl-Cό alkyl)0-, -OH, (Cl-Cό alkyl)S(0)m-, (Cl -Cό alkyl)C(0)NH-, H2N-C(NH)-, (Cl -Cό alkyl)C(O)-, (Cl -Cό alkyl)OC(O)-, N3 C1 -C6 alkyl)OC(0)NH-, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl and -C20 alkyl. Lines drawn into the ring systems from substituents (such as from R 2 , R , R etc.) indicate that the indicated bond may be attached to any of the substitutable ring carbon atoms. The substituent illustrated by the stmcture is a simplified representation of a phenyl ring having five (5) substituents (hydrogens and/or non-hydrogens) and may also be represented by the stmcture The moiety described as where any two of R°\ R6b ? R6C ? Rod a nd R6 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH, -CH=CH-CH-, -(CH2)4- and -(CH2)4- includes the following stmctures: It is understood that such fused ring moieties may be further substituted by the remaining R 6a , R6b, R6C, Rod and/or R6e as defined hereinabove. Preferably, Rla and Rib are independently selected from: hydrogen, RHC(0)0-, -N(RlO) 2 , R!0C(O)NR10-, Rl0 O - or unsubstituted or substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted phenyl, -N(RlO) 2 , RlOO- and R!0C(O)NR10-. Preferably, R 2 is selected from: a) hydrogen, b) C3-C10 cycloalkyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, CN, Nθ2, Rl°C(0)- or-N(RlO) 2 , c) unsubstituted C 1 -Co alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl2θ-, Rl lS(0) m -, R1°C(0)NR10-, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0-. Preferably, R3 is selected from: hydrogen, halogen, trifluoromethyl, trifluoromethoxy and Cl-Cό alkyl. Preferably, R and R^ are hydrogen. Preferably, R&A R6b, ROC, Rod an d R°e are independently selected from: a) hydrogen, b) C3-C10 cycloalkyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)πr, CN, Nθ2, Rl°C(0)- or -N(RlO) , c) unsubstituted C 1 -Co alkyl; d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, C3-C10 cycloalkyl, Rl 2 0-, Rl lS(0) m -, Rl0c(O)-or-N(Rl°)2;or any two of R^a, R6b, R6C 5 Rod a nd R^e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-- Preferably, R8 is independently selected from: a) hydrogen, and b) aryl, substituted aryl, heterocycle, substituted heterocycle, C l -Cό perfluoroalkyl or CN. Preferably, R9 is hydrogen, halogen, CF3 or methyl. Preferably, RlO is selected from H, Cl -Cό alkyl and benzyl. Preferably, Al and A 2 are independently selected from: a bond, -C(O)NR l0_, -NR I OC(O)-, O, -N(R 10)-, -S(O)2N(R 1 ). and Preferably, V is selected from hydrogen, heterocycle and aryl. More preferably, V is phenyl. Preferably, W is selected from imidazolinyl, imidazolyl, oxazolyl, pyrazolyl, pyyrohdinyl, thiazolyl and pyridyl. More preferably, W is selected from imidazolyl and pyridyl. Preferably, X is a bond, -NR J 0c(O)-, O or -C(=0)-. Most preferably, X is a bond. Preferably, n and r are independently 0, 1 , or 2. Preferably s is 0. Preferably t is 1. Preferably, the moiety V - A 1 (CR 1 a 2 ) n A 2 (CR 1 (CR 1 b 2 ) p - X -(CR 1 2 )- p is selected from: and It is intended that the definition of any substituent or variable (e.g., R l a, 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 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 1-22, 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 2 , R^ and R^, as shown in the Schemes, represent the substituents R 2 , R , R , 5 ? R6a, R6b, R6C, R 6d and R 8 ; although only one such R 2 , R6 or R 8 is present in the intermediates and products of the schemes, it is understood that the reactions shown are also applicable when such aryl or heteroaryl moieties contain multiple substituents. 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 alkyla¬ tion reactions described in the Schemes. Aryl-aryl coupling is generally described in "Comprehensive Organic Functional Group Transformations," Katritsky et al. eds., pp 472-473, Pergamon Press (1995). Synopsis of Schemes 1 -22: The requisite intermediates are in some cases commercially available, or can be prepared according to literature procedures, for the most part. Schemes 1- 13 illustrate synthesis of the instant biaryl compound which incorporate a preferred benzylimidazolyl sidechain. Thus, in Scheme 1 , for example, a biaryl intermediate that is not commercially available may be synthesized by methods known in the art. Thus, a suitably substituted phenyl boronic acid I may be reacted under Suzuki coupling conditions (Pure Appl. Chem., 63:419 (1991)) with a suitably substituted halogenated benzoic acid, such as 4-bromobenzoic acid, to provide the biaryl carboxylic acid II. The acid may be reduced and the triflate of the intermediate alcohol III may be formed in situ and coupled to a suitably substituted benzylimidazolyl IV to provide, after deprotection, the instant compound V. Schemes 2-5 illustrate other methods of synthesizing the key alcohol intermediates, which can then be processed as described in Scheme 1. Thus, Scheme 2 illustrates the analogous series of biaryl alcohol forming reactions starting with the halogenated biarylaldehyde. Scheme 3 illustrates the reaction wherein the "terminal" phenyl moiety is employed in the Suzuki coupling as the halogenated reactant. Such a coupling reaction is also compatible when one of the reactants incorporates a suitably protected hydroxyl functionality as illustrated in Scheme 4. Negishi chemistry (Org. Synth., 66:67 (1988)) may also be employed to form the biaryl component of the instant compounds, as shown in Scheme 5. Thus, a suitably substituted zinc bromide adduct may be coupled to a suitably substituted aryl halide in the presence of nickel (II) to provide the biheteroaryl VII. The aryl halide and the zinc bromide adduct may be selected based on the availability of the starting reagents. Scheme 6 illustrates the preparation of a suitably substituted biphenyl ethyl bromide which could also be utilized in the reaction with the protected imidazole as described in Scheme 1. Preparation of biaryl intermediates having a suitably substituted alkyl moiety on the carbon adjacent to the eventual point of attachment to the rest of the instant compounds is illustrated in Scheme 6a. Thus a suitably substituted biaryl carboxylic acid is first converted to the amide and then the phenyl lithium is prepared and reacted in situ with a suitably substituted alkanal to provide the hydroxyalkane side- chain. The amide is then converted sequentially to the hydroxymethyl- biaryl Ilia or bromomethylbiaryl intermediates which may then be utilized in reactions that have been previously described or will be described below. As illustrated in Scheme 7, the sequence of coupling reactions may be modified such that the biphenyl bond is formed last. Thus, a suitably substituted imidazole may first be alkylated with a suitably substituted benzyl halide to provide intermediate VIII. Intermediate VIII can then undergo Suzuki type coupling to a suitably substituted phenyl boronic acid. Scheme 8 illustrates synthesis of an instant compound wherein a non-hydrogen R j s incorporated in the instant compound. Thus, a readily available 4-substituted imidazole IX may be selectively iodinated to provide the 5-iodoimidazole X. That imidazole may then be protected and coupled to a suitably substituted benzyl moiety to provide intermediate XI. Intermediate XI can then undergo the alkylation reactions that were described hereinabove. Scheme 9 illustrates synthesis of instant compounds that incorporate a preferred imidazolyl moiety connected to the biaryl via an alkyl amino, sulfonamide or amide linker. Thus, the 4-aminoaIkylimidazole XII, wherein the primary amine is protected as the phthalimide, is selectively alkylated then deprotected to provide the amine XIII. The amine XIII may then react under conditions well known in the art with various activated biaryl moieties to provide the instant compounds shown. Compounds of the instant invention wherein the Al(CRl a 2)nA 2 (CRl 2)n linker is oxygen may be synthesized by methods known in the art, for example as shown in Scheme 10. The suitably substituted phenol XIV may be reacted with methyl N-(cyano)methanimidate to provide the 4-phenoxyimidazole XV. After selective protection of one of the imidazolyl nitrogens, the intermediate XVI can undergo alkylation reactions as described for the benzylimidazoles hereinabove. Scheme 1 1 illustrates an analogous series of reactions wherein the (CRlb2)pX(CRl D 2)p linker of the instant compounds is oxygen. Thus, a suitably substituted haloaryl alcohol, such as , is reacted with methyl N-(cyano)methanimidate to provide intermediate XVI. Intermediate XVI is then protected and, if desired to form a compound of a preferred embodiment, alkylated with a suitably protected benzyl. The intermediate XVII can then be coupled to a second aryl moiety by Suzuki chemistry to provide the instant compound. Compounds of the instant invention wherein the Al (CRl a 2)nA (CR l a 2)n linker is a substituted methylene may be synthesized by the methods shown in Scheme 12. Thus, the N-protected imidazolyl iodide XVIII is reacted, under Grignard conditions with a suitably protected benzaldehyde to provide the alcohol XIX. Acylation, followed by the alkylation procedure illustrated in the Schemes above (in particular, Scheme 1 ) provides the instant compound XX. If other Rl substituents are desired, the acetyl moiety can be manipulated as illustrated in the Scheme. Grignard chemistry may also be employed to form a substituted alkyl linker between the biaryl and the preferred W (imidazolyl) as shown in Scheme 13. Similar substituent manipulation as shown in Scheme 12 may be performed on the fully functionahzed compound which incorporates an R l b hydroxyl moiety. SCHEME 1 Pd(PPh 3 ) 4 SCHEME 1 (continued SCHEME 2 SCHEME 3 SCHEME 4 SCHEME 5 SCHEME 6 SCHEME 6a SCHEME 7 Pd(PPh 3 ) 4 SCHEME 8 H H Nal, NaHCQ 3 , l 2 TrCI, NEt IX X SCHEME 9 SCHEME 10 H Tr XV XVI XVI SCHEME 12 Tr SCHEME 12 (continued) SCHEME 13 Schemes 16-20 illustrate reactions wherein the moiety V - A 1 (CR 1 a 2 ) n A 2 (CR - (CR 1 b 2 ) p -X incorporated in the compounds of the instant invention is represented by other than a substituted imidazole-containing group. Thus, the intermediates whose synthesis are illustrated in Schemes hereinabove and other biheteroaryl intermediates obtained commercially or readily synthesized, can be coupled with a variety of aldehydes. 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 14). Grignard chemistry may be utilized, as shown in Scheme 14, to incorporate the biaryl moiety. Thus, a suitably substituted biaryl Grignard reagent is reacted with an aldehyde to provide the C-alkylated instant compound XXI. Compound XXI can be deoxygenated by methods known in the art, such as a catalytic hydrogention, then deprotected with trifluoroacetic acid in methylene chloride to give the final compound XXII. The final product XXII may be isolated in the salt form, for example, as a trifluoroacetate, hydrochloride or acetate salt, among others. The product diamine XXII can further be selectively protected to obtain XXIII, which can subsequently be reductively alkylated with a second aldehyde to obtain XXIV. Removal of the protecting group, and conversion to cyclized products such as the dihydroimidazole XXV can be accomplished by literature procedures. If the biaryl subunit reagent is reacted with an aldehyde which also has a protected hydroxyl group, such as XXVI in Scheme 15, the protecting groups can be subsequently removed to unmask the hydroxyl group (Schemes 15, 16). 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 XXX. In addition, the fully deprotected amino alcohol XXXI can be reductively alkylated (under conditions described previously) with a variety of aldehydes to obtain secondary amines, such as XXXII (Scheme 16), or tertiary amines. The Boc protected amino alcohol XXVIII can also be utilized to synthesize 2-aziridinylmethylbiaryl such as XXXIII (Scheme 17). Treating XXVIII with l ,l '-sulfonyldiimidazole and sodium hydride in a solvent such as dimethylformamide led to the formation of aziridine XXXIII . The aziridine is reacted with a nucleophile, such as a thiol, in the presence of base to yield the ring- opened product XXXIV . In addition, the biaryl subunit reagent can be reacted with aldehydes derived from amino acids such as O-alkylated tyrosines, according to standard procedures, to obtain compounds such as XL, as shown in Scheme 18. When R' is an aryl group, XL can first be hydrogenated to unmask the phenol, and the amine group deprotected with acid to produce XLI. Alternatively, the amine protecting group in XL can be removed, and O-alkylated phenolic amines such as XLII produced. Schemes 19-22 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. SCHEME 14 NHBoc I SCHEME 14 (continued) XXV SCHEME 15 SCHEME 15 (continued) XXIX SCHEME 16 NHBoc XXXI SCHEME 17 NHBoc XXVIII XXXIII SCHEME 18 XXXV XXXVI XXXVII XXXVIII SCHEME 18 (continued) SCHEME 19 NaBH 4 (excess) SCHEME 20 SCHEME21 NaBH 4 (excess) SCHEME 22 excess NaBH . 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 fa esyl- 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 vimses (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 ΆLFASEB 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 combina- tion with pharmaceutically acceptable carriers or diluents, optionally with known adjuvants, such as alum, in a pharmaceutical composition, according to standard pharmaceutical practice. The compounds can be administered orally or parenterally, including the intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical routes of administration. For oral use of a chemotherapeutic compound according to this invention, the selected compound may be administered, for example, in the form of tablets or capsules, or as an aqueous solution or suspension. In the case of tablets for oral use, carriers which are commonly used include lactose and com starch, and lubricating agents, such as magnesium stearate, are commonly added. For oral administration in capsule form, useful diluents include lactose and dried com starch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous use, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled in order to render the preparation isotonic. The 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 vimses 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 famesyl pyrophosphate and, in one of the mixtures, a compound of the instant invention. After the assay mixtures are incubated for an sufficient period of time, well known in the art, to allow the FPTase to famesylate the substrate, the chemical content of the assay mixtures may be determined by well known immunological, radiochemical or chromatographic techniques. Because the compounds of the instant invention are selective inhibitors of FPTase, absence or quantitative reduction of the amount of substrate in the assay mixture without the compound of the instant invention relative to the presence of the unchanged substrate in the assay containing the instant compound is indicative of the presence of FPTase in the composition to be tested. It would be readily apparent to one of ordinary skill in the art that such an assay as described above would be useful in identifying tissue samples which contain famesyl-protein transferase and quantitat- ing the enzyme. Thus, potent inhibitor compounds of the instant invention may be used in an active site titration assay to determine the quantity of enzyme in the sample. A series of samples composed of aliquots of a tissue extract containing an unknown amount of famesyl- protein transferase, an excess amount of a known substrate of FPTase (for example a tetrapeptide having a cysteine at the amine terminus) and famesyl pyrophosphate are incubated for an appropriate period of time in the presence of varying concentrations of a compound of the instant invention. The concentration of a sufficiently potent inhibitor (i.e., one that has a Ki substantially smaller than the concentration of enzyme in the assay vessel) required to inhibit the enzymatic activity of the sample by 50% is approximately equal to half of the concentration of the enzyme in that particular sample. EXAMPLES Examples provided are intended to assist in a further understanding of the invention. Particular materials employed, species and conditions are intended to be further illustrative of the invention and not limitative of the reasonable scope thereof. EXAMPLE 1 1 -(4-BiphenylmethyD-5-(4-cyanobenzyl)imidazole hydrochloride salt Step A: l -Trityl-4-(4-cvanobenzvD-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 a-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 -tritylimidazole ( 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 NH4CI solution ( 100 mL) and the mixture stirred for 2 hours. Saturated aq. NaHC03 solution was added to give a pH of 8 and the solution was extracted with EtOAc (2 x 250 mL), dried (MgSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 0-20% EtOAc inCH2Cl2) to afford the title compound as a white solid. l H NMR (CDC13, 400Mz) δ (7.54 (2H, d, J=7.9Hz), 7.38( 1H, s), 7.36-7.29 (1 1 H, m), 7.15-7.09(6H, m), 6.58(1H, s) and 3.93(2H, s) ppm. Step B: 1 -(4-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole hydochloride salt To l -trityl-4-(4-Cyanobenzyl)-imidazole (608mg, 1.43 mmol) in acetonitrile (2 mL) was added 4-chloromethylbiphenyl (290mg, 1.43 mmol) and the mixture heated at 55°C for 16 hours. The residue was dissolved in methanol (30 ml) and heated at reflux for 20 minutes, 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, 5% MeOH in CH2C12) to afford the imidazole which was converted to the HCI salt by treatment with one equivalent of HCI in aqueous acetonitrile. Evaporation of solvent in vacuo afforded the title compound as a white powder. Anal. Calcd for C24H19N3- 1.00 HCI: C, 74.70; H, 5.22; N, 10.89. Found: C, 74.70; H, 5.31 ; N, 10.77. FAB MS 350 (MH+) iH NMR CD3OD δ 9.03(1H, s), 7.65-7.50(5H, m), 7.44(2H, t, J=7.5Hz), 7.39(1 H, s), 7.35(1H, t, J=7.3Hz), 7.26(2H, d, J=8.1Hz), 7.20(2H, d, J=8.1 Hz), 5.42(2H, s) and 4.17(2H, s) ppm. EXAMPLE 2 1 -(2-Biphenylmethyl)-5-(4-cyanobenzyl)imidazoIe hydrochloride salt To l -trityl-4-(4-cyanobenzyl)-imidazole (250 mg , 0.588 mmol) in acetonitrile (1 mL) was added 2(bromomethyl)biphenyl (0.108 mL, 0.591 mmol) and the mixture heated at 55°C for 16 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (10 mL) and heated at reflux for 30 minutes, cooled and the solvent evaporated in vacuo. The residue was partitioned between sat. aq. NaHCθ3 solution and CH2CI2. The organic layer was dried, (NaSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (silica gel, 3%MeOH in CH2CI2) to afford the imidazole, which was converted to the HCI salt by treatment with one equivalent of HCI in aqueous acetonitrile. Evaporation of solvent in vacuo afforded the title compound as a white solid. Anal. Calcd. for C24H19N3- 1.00HC1: C, 74.70; H, 5.22; N, 10.89. Found: C, 74.60; H, 5.26; N, 10.97. FAB MS 350 (MH+) i H NMR (CD3OD, 400MHz) δ 8.39( 1H, s), 7.59(2H, d, J=8.4Hz), 7.48(1H, t, J=6.5Hz), 7.46-7.36(3H, m), 7.30(1H, d, J=6.6Hz), 7.28- 7.18(3H, m), 7.13(2H, d, J=8.1 Hz), 5.31 (2H, s) and 3.78(2H, s) ppm. EXAMPLE 3 1 -(3-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole trifluoroacetate salt Step A: 3-(Bromomethyπbiphenyl To a solution of 3-phenyltoluene (1.80 mL, 10.9 mmol) in carbon tetrachloride (50 mL) was added N-bromosuccinimide (2.124 g, 1 1.93 mmol) and the mixture heated to 70°C. AIBN (50 mg, 0.30 mmol) was added and the mixture refluxed for 30 mins. Additional AIBN was added (50 mg, 0.30 mmol) and the mixture refluxed for 16 hours. The reaction was cooled, filtered, and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 5% EtOAc in hexanes) to afford the title compound as a white solid. Step B: 1 -(3-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole trifluoroacetate salt To l -trityl-4-(4-cyanobenzyl)-imidazole (251 mg , 0.590 mmol) in acetonitrile ( 1 mL) was added 3-(bromomethyl)biphenyl (145 mg, 0.587 mmol) and the mixture heated at 55°C for 16 hours. The residue was dissolved in methanol (10 mL) and heated at reflux for 30 minutes, cooled and evaporated to dryness. The residue was partitioned between sat. aq. NaHCθ3 solution and CH2CI2. The organic layer was dried, (NaS04) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 2-5% MeOH in CH2CI2) and further purified by preparative HPLC, (gradient elution, 95 :5 to 5:95% wateπacetonitrile containing 0.1 % trifluoroacetic acid) to afford the title compound. Anal. Calcd. for C24H 19N3 I .IO C2HO2F3 O.65 H2O: C, 64.68; H, 4.43; N, 8.64. Found: C, 64.68; H, 4.43; N, 8.50. FAB MS 350 (MH+) i H NMR (CD3OD, 400MHz) δ 9.05(1 H, d, J=1.6Hz), ), 7.58(1H, d, J=7.6Hz), 7.55-7.48(4H, m), 7.48-7.32(5H, m), 7.29(1H, s), 7.24(2H, d, 8.1Hz), 7.13(1H, dd, J=7.7 and 0.8Hz), 5.46(2H, s) and 4.20(2H, s) pp . EXAMPLE 4 l-(4-Cyanobenzyl)-5-(4'-phenylbenzamido)ethyl-imidazole Step A: l -(4-Cvanobenzyl)-5-aminoethylimidazole NG.pivaloyloxymethyl-Na-phthaloylhistaminel (4.55 g, 12.8 mmol) and a-bromo-p-tolunitrile (3.77 g, 19.2 mmol) were dissolved in acetonitrile (70 mL) and heated at 55°C for 4 hours, cooled to room temperature, filtered and the imidazolium salt retained as a white solid . The filtrate was evaporated in vacuo to a volume of 30 mL and heated at 55°C for 16 hours. The solution was cooled and the white solid collected by filtration. The solids were combined, and dissolved in ethanol (50 mL). Hydrazine (0.287 mL, 9.06 mmol) was added and the mixture heated at reflux for 16 hours. Dimethyl phthalate (2.22 mL, 13.57 mmol) was added and reflux was continued for 6 hours. The reaction mixture was cooled to 0°C, the solid was removed by filtration, concentrated to dryness, and the residue chromatographed (Siilica gel, 3% CH2CI2 then 8%NH4θH in CH3OH) to afford the title compound. lH NMR (CD3OD, 400MHz) δ 7.76 (1H, s), 7.74 (2H, d, J = 8 Hz, ), 7.27 ( 2H, d, J = 8 Hz), 6.88 ( 1H, s), 5.35 (2H, s), 2.76 (2H, t, J = 6 Hz) and 2.60(2H, t, J = 6 Hz) ppm. 1. C. Emmett, F. H. Holloway, and J. L. Turner, J. Chem. Soc, Perkin Trans. 7 , 1341 , ( 1979)) Step B: l- ( 4-Cvanobenzyl ) -5- ( 4'-phenylbenzamido)ethyl-imidazole To a solution ofl -(4-cyanobenzyl)-5-aminoethylimidazole (107 mg, 0.358 mmol), 4-phenylbenzoic acid (70.9 mg, 0.358 mmol), 3-hydroxy-l ,2,3-benzotriazin-4(3H)-one, (72.6 mg, 0.445 mmol) and triethylamine (0.215 mL , 1.54 mmol) in DMF (4.0 mL) was added 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, EDC, (83.3mg, 0.435 mmol) and the mixture stirred for 16 hours at ambient temperature. The reaction was partitioned between sat. aq. NaHCθ3 solution and EtOAc. The organic layer was dried, (Na2Sθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 5% MeOH in CH2CI2) to afford the imidazole which was converted to the HCI salt by treatment with one equivalent of HCI in aqueous acetonitrile. Evaporation of the solvent in vacuo afforded the title compound as a white solid. Anal. Calcd. for C26H22N40- 1.00 HC1 0.95 H2O: C, 67.88; H, 5.46; N, 12.18. Found: C, 67.83; H, 5.47; N, 1 1.97. FAB MS 407 (MH+) 1H NMR (CD3OD, 400MHz) δ 9.00(1H, s), ), 8.67(1H, m), 7.90- 7.60(8H, m),7.58-7.30(6H, m), 5.65(2H, s), 3.65(2H, t, J=5.4Hz) and 2.95(2H, t, J=6.4Hz) ppm. EXAMPLE 5 l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt Step A: 4-(2-trifluoromethylphenyl)benzoic acid To a solution of 4-carboxybenzeneboronic acid (1.218 g, 7.340 mmol) and Na2C03 (2.40 g, 22.6 mmol) in water (75 mL) was added p-dioxane (75 mL). This mixture was treated sequentially with 2-iodobenzotrifluoride (1.05 mL, 7.48 mmol) and palladium (II) acetate ( 151 mg, 0.673 mmol) and allowed to stir at ambient temperature for 16 hours. The solvent was evaporated in vacuo. To the residue was added EtOAc (400 mL) and water (300 mL). The aqueous layer was acidified to pH 1 with 1.0 N aq. HCI and the layers separated. The aqueous layer was extracted with EtOAc (2 x 200 mL). The organic extracts were combined, washed with brine (200 mL), 5% aq. Na2S2θ3 (200 mL), saturated NaCl (200 mL), dried (Na2Sθ4), and the solvent evaporated in vacuo to afford the title compound as a yellow solid. i H NMR (CDCl3, 400MHz) d 8.14(2H, d, J=8.1Hz), ), 7.77(1H, d, J=7.9Hz), 7.60(1 H, t, J=7.5Hz), 7.52(1H, t, J=7.3Hz), 7.44(2H, d, J=8.1Hz) and 7.33(1 H, d, J=7.5Hz) ppm. Step B: 4-(2'-trifluoromethylphenyl)benzvIalcohol To a solution of 4-(2'-trifluoromethylphenyl)benzoic acid (1.525 g, 5.728 mmol) in THF (25 mL) at 0°C was added 1.0 M lithium aluminum hydride in tetrahydrofuran (12.0 mL, 12.0 mmol) over 10 minutes. The reaction was allowed to stir at ambient temperature for 3 hours, cooled to 0°C, and quenched by dropwise addition of water (0.5 mL), 4 N aq. NaOH (0.5 mL), and water (1.5 mL). The reaction was filtered through a pad of Celite and the filtrate evaporated in vacuo. The residue was chromatographed (Silica gel, 20% EtOAc in hexanes) to afford the title compound. iH NMR (CDC13, 400MHz) δ 7.74(1 H, d, J=7.7Hz), ), 7.55(1 H, d, J=7.4Hz), 7.47(1H, t, J=7.4Hz), 7.41(2H, d, J=7.9Hz), 7.36-7.30(3H, m) and 4.78(2H, s) ppm. Step C: 1 -(2'-Trif_uoromethyl-4-biphenylmethyl)-5-(4- cvanobenzvDimidazole hydrochloride salt To a solution of 4-(2'-trifluoromethylphenyl) benzylalcohol (362 mg, 1.44 mmol) and diisopropylethylamine (0.260 mL, 1.49 mmol) in dichloromethane (6.0 mL) at -78°C was added trifluoro- methanesulfonic anhydride (0.250 mL, 1.49 mmol) and the mixture stirred at -78°C for 1 hour. To this mixture was added a solution of l-trityl-4-(4-cyanobenzyl)-imidazole (613 mg , 1.44 mmol) in dichloromethane (6.0 mL). The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (1 mL), heated at reflux for I hour, and the solvent evaporated in vacuo. The residue was partitioned between CH2CI2 and sat. aq. NaHC03 solution. The organic layer was dried, (Na2Sθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 0-2% MeOH in CH2CI2) and further purified by preparative HPLC, (gradient elution, 95 :5 to 5:95% water: acetonitrile containing 0.1 % trifluoroacetic acid) to afford the trifluoroacetic acid salt. The salt was partitioned between EtOAc and sat. aq. NaHCθ3 solution, the organic layer dried, (Na2S04) and the solvent evaporated in vacuo to afford the imidazole. The amine was converted to the HCI salt by treatment with 1.0 equivalent of HCI in aqueous acetonitrile. Evaporation of the solvent in vacuo afforded the title compound as a white solid. Anal. Calcd. for C25H18N3F3 I .OO HC1-0.85 H2O: C, 64.00; H, 4.45; N, 8.96. Found: C, 64.05; H, 4.24; N, 8.80. FAB MS 418 (MH+) IH NMR (CD3OD, 400MHz) δ 9.10(1H, s), ), 7.78(1H, d, J=7.8Hz), 7.70-7.62(3H, m), 7.56( 1H, t, J=7.5Hz), 7.43(1H, s), 7.38-7.24(5H, m), 7.19(2H, d, 8.1Hz)), 5.48(2H, s) and 4.18(2H, s) ppm. EXAMPLE 6 1 -(4-Biphenylethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt Step A: 4-Biphenylethanol The 4-biphenylethanol was prepared using the protocol described in example 5, step B and 4-biphenylacetic acid. H NMR (CDCI3, 400MHz) δ .60-7.55(4H, m), 7.43(2H, t, J=7.8Hz), 7.37-7.28(3H, m), 3.91 (2H, q, J=6.4Hz), 2.92(2H, t, J=6.6Hz), 1.40(1 H, t, J=5.8Hz) ppm. Step B: l -(4-Biphenylethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, step C and 4-biphenylethanol Anal. Calcd. for C25H21 N3T .OO HC1 0.30 H2O: C, 74.08; H, 5.62; N, 10.37. Found: C, 74.40; H, 5.52; N, 9.98. FAB MS 364 (MH+) IH NMR (CDC13, 400MHz) δ 8.78(1H, d, J=1.6Hz), 7.70(2H, d, J=8.2Hz), 7.62-7.54(4H, m), 7.48-7.30(5H, m), 7.20-7.12(3H, m), 4.43(2H, t, J=6.9Hz), 4.04(2H, s), and 3.10(2H, t, J=6.8Hz) ppm. EXAMPLE 7 1 -(2'-Bromo-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt Step A: 4-(2'-Bromophenyl)benzaldehyde To a solution of 4-formylbenzeneboronic acid ( 1.19 g, 7.96 mmol) and Na2Cθ3 (1.68 g, 15.8 mmol) in water (60 L) was added p-dioxane (60 mL). This mixture was treated sequentially with 2-bromo iodobenzene (2.25g, 7.95 mmol) and palladium (II) acetate (159 mg, 0.708 mmol) and allowed to stir at ambient temperature for 16 hours. The solvent was evaporated in vacuo. To the residue was added EtOAc (400 mL) and water (300 mL). The aqueous layer was extracted with EtOAc (2 x 200 mL). The organic extracts were combined, washed with brine (200 mL), 5% aq. Na2S2θ3 (200 mL), brinel (200 mL), dried, (Na2S04) and the solvent evaporated in vacuo to afford the title compound which was used in the next step without furthur purification. Step B: 4-(2'-Bromophenyl)benzyl alcohol To a solution of 4-(2'-bromophenyl)benzaldehyde 1.55g, 7.95 mmol) in ethanol (15 mL) at 0°C was added sodium borohydride (2.22g, 58.7 mmol) and the reation stirred for 1 hour. The reaction was quenched with saturated aq. NH4CI and extracted into diethyl ether. The organic extracts were washed with brine, dried, (Na2S04) and evaporated in vacuo. The residue was purified by chromatography (Silica gel, 25% EtOAc in hexanes) to afford the title compound as a colourless oil. lH NMR (CDC13, 400MHz) δ 7.66( 1 H, dd, J=8.1 and 1.1 Hz), 7.45- 7.30(6H, m), 7.23(1 H, m) and 4.66(2H, s) ppm. Step C: 1 -(2'-Bromo-4-biphenylmethyl)-5-(4-cyanobenzyl)- imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, step C and 4-(2'-bromophenyl) benzyl alcohol. Anal. Calcd. for C24HI8N3BP I .OO HCM .46 H2O: C, 58.70; H, 4.50; N, 8.56. Found: C, 58.66; H, 4.10; N, 8.27. FAB MS 430(MH+) IH NMR (CD3OD 400MHz) δ 9.1 1(1H, s), 7.68(1H, d, J=8.1Hz), 7.62(2H, d, J=8.3Hz), 7.50-7.16(10H, m), 5.48(2H, s) and 4.20(2H, s) ppm. EXAMPLE 8 l -(2'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps A-C using 2-iodotoluene. Anal. Calcd. for C25H21 N3T .OO HC1-0.65 H2O: C, 73.13; H, 5.47; N, 10.23. Found: C, 73.16; H, 5.70; N, 10.20. IH NMR (CD3OD 400MHz) δ 9.06(1H, d, J=1.6Hz), 7.62(2H, d, J=8.4Hz), 7.42(1 H, s), 7.35-7.10(10H, m), 5.44(2H, s), 4.21(2H, s) and 2.20(3H, s) ppm. EXAMPLE 9 l -(2'-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps A-C using 2-trifluoromethoxy- iodobenzene. iH NMR (CD3OD 400MHz) δ 9.08(1H, d, J=1.6Hz), 7.61 (2H, d, J=8.4Hz), 7.52-7.38(7H, m), 7.29(2H, d, J=8.1 Hz), 7.23(2H, d, J=8.1Hz), 5.47(2H, s) and 4.17(2H, s) ppm. EXAMPLE 10 l -(4-(3',5'-dichloro)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps A-C using 3,5-dichloroiodobenzene. Anal. Calcd. for C24Hl7N3C_2- 1.00 HC1 0.35 H2O: C, 62.52; H, 4.09; N, 9.1 1. Found: C, 62.57; H, 3.88; N, 9.04. FAB MS 418(MH+) iH NMR (CD3OD 400MHz) δ 9.08(1H, s), 7.57(6H, m), 7.44(2H, d, J=4.2Hz), 7.32-7.20(4H, m), 5.46(2H, s) and 4.17(2H, s) ppm. EXAMPLE 1 1 1 -(2'-Methoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps A-C using 2-methoxyiodobenzene. Anal. Calcd. for C25H21N3O I .OO HCI: C, 72.19 H, 5.33; N, 9.79. Found: C, 72.12; H, 5.31 ; N, 10.10. IH NMR (CD3OD, 400MHz) δ 9.05(1H, d, J=1.3Hz), 7.60(2H, d, J=7.2Hz), 7.44(2H, d, J=8.2Hz), 7.41 (1 H, s), 7.38-7.20(4H, m), 7.16(2H, d, J=8.1 Hz), 7.07( 1 H, d, J=8.0Hz), 7.01 (IH, t, J=7.5Hz), 5.42(2H, s), 4.19(2H, s) and 3.80(3H, s) ppm. EXAMPLE 12 1 -(2'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps A-C using 2-chloro iodobenzene. Anal. Calcd. for C24H I 8N3 LOO HCI- 0.20H2O: C, 68.00 H, 4.61 ; N, 9.91. Found: C, 68.00; H, 4.77; N, 9.56. iH NMR (CD3OD, 400MHz) δ 9.09(1 H, d, J=1.3Hz), 7.61(2H, d, J=7.2Hz), 7.55-7.25(9H, m), 7.20(2H, d, J=8.1Hz), 5.47(2H, s) and 4.21(2H, s) ppm. EXAMPLE 13 l -(2-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrobromide salt Step A: 2-Chloro-4-phenyl toluene A mixture of 2-chloro-4-iodotoluene(2.94 g, 1 1.63 mmol), phenyl boronic acid (1.56 g, 12.79 mmol), barium hydroxide (5.50 g, 17.44 mmol), DME (3 mL) and water (15 mL) was purged with dry argon. Tetrakis(triphenyl-phosphine)palladium(0) (672 mg, 0.58 mmol) was added, and the resultant solution was stirred at 80°C for 4 hours. The solvents were evaporated in vacuo, and the residue partitioned between EtOAc and water and acidified with 1 M aq. HCI. The aqueous extract was separated, and extracted with EtOAc. The organic extracts were combined, washed with NaHC03 and 5% aq. Na2S2θ3, dried, (Na2Sθ4) filtered and the solvent evaporated in vacuo. The residue was purified by chromatography (Silica gel, 10% EtOAc in hexanes) to afford the title compound. 1 H NMR (CDC13 400MHz) δ 7.62-7.54 (3H, m), 7.48-7.25(5H, m) and 2.43(3H, s) ppm. Step B: l-(Bromomethyl)-2-chloro-4-biphenyl To a solution of 2-chloro-4-phenyl toluene (91 1 mg, 4.50 mmol) in carbon tetrachloride (18 mL) was added N-bromosuccinimide (800 mg, 4.50 mmol) and the mixture heated to 70°C. AIBN ( 16.4 mg, 0.10 mmol) was added and the mixture refluxed for 2 hours. The reaction was cooled, filtered, and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 15% CH2CI2 in hexanes) to afford the title compound as a white solid. IH NMR (CDCI3, 400MHz) δ 7.62(1H, d, J=1.7Hz), 7.60-7.34(7H, m) and 4.65(2H, s) ppm. Step C: 1 -(2-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl)- imidazole hvdrobromide salt. A suspension of l-(bromomethyl)-2-chloro-4-biphenyl (500mg, 1.78 mmol), l-trityl-4-(4-cyanobenzyl)-imidazole (756mg, 1.78 mmol) in acetonitrile (5 mL) was stirred at 55°C for 16 hours. The solvent was evaporated in vacuo and the residue dissolved in methanol and stirred at reflux for 1 hour. The solvent was evaporated in vacuo. The residue suspended in EtOAc (10 mL) and the product isolated as a white solid by filtration. The solids were washed with EtOAc (5 mL) and diethylether (10 mL) and dried in vacuo. Anal. Calcd. for C24HI 8N3CM .OO HBr- 0.30H2O C, 61.31 H, 4.20 N, 8.94. Found: C, 61.61 ; H, 4.23; N, 8.55. IH NMR (CD3OD, 400MHz) δ 8.99(1 H, d, J=1.4Hz), 7.65(1 H, d, J=2.3Hz), 7.62-7.54(4H, m), 7.54-7.43(4H, m), 7.40(1 H, m), 7.29(2H, d, J=8.4Hz), 7.1 1(1H, d, J=7.8Hz), 5.52(2H, s) and 4.24(2H, s) ppm. EXAMPLE 14 1 -(3-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 13, steps A-C using 3-chloro-4-iodotoluene. The imidazole was isolated by chromatography (Silica gel, 2-3% MeOH in CH2C12), and converted to the HCI salt by treatment with HCI gas in EtOAc and evaporation of the solvent in vacuo. Anal. Calcd. for C24H18CIN3T .OO HCI- 0.30H2O: C, 67.71 H, 4.64; N, 9.87. Found: C, 67.75; H, 4.69; N, 9.73. IH NMR (CD3OD, 400MHz) δ 9.19(1 H, s), 7.58(2H, d, J=8.0Hz), 7.55-7.30(6H, m), 7.30-7.00(5H, m), 5.45(2H, s) and 4.23(2H, s) ppm. EXAMPLE 15 l -(4-(3',5'-Bis-trifluoromethyl)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt Step A: Methyl 4-(3 , .5'-Bis-trifluoromethylphenyl)benzoate To a solution of 3',5'-Bis-trifluoromethylbenzeneboronic acid (0.430 g, 1.57 mmol) and barium hydroxide octahydrate (0.675 g, 2.14 mmol) in water (1.5 mL) was added DME (8 mL). This mixture was treated sequentially with methyl-4-iodobenzoate (0.375g, 1.43 mmol) and tetrakis triphenylphosphine palladium (0) (83 mg, 0.07 mmol) and heated at 80°C for 5 hours. The reaction cooled, acidified to pH 1 with aq. HC ^d extracted with EtOAc (2 x 50 mL) The combined organic e: ts were washed with sat. aq. NaHC03, brine, dried, (Na2S04) an _e solvent evaporated in vacuo. The residue was dissolved in methanol (50 mL), saturated with gasseous HCI and stirred for 16 hours at ambient temperature. The solvent was evaporated in vacuo to afford the title compound as a solid. IH NMR (CDC13, 400MHZ) δ 8.17(2H, d, J=8.4 Hz), 8.04(2H, s), 7.91 (1H, s), 7.68(2H, d, J=8.4Hz) and 3.97(3H, s) ppm. Step B: 1 -(4-(3',5'-Bis-trifluoromethyl)-biphenylmethyl)-5-(4- cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, steps B-C using methyl- {4-(3',5'-bis- trifluoromethylphenyl)benzoate. Anal. Calcd. for C26H17N3F6T .8O HCI C, 60.69; H, 3.49; N, 8.17. Found: C, 60.69; H, 3.35; N, 7.92. FAB MS 486(MH+) iH NMR (CD3OD ,400MHz) δ 9.70(1 H, d, J=1.4Hz),8.16(2H, s), 7.98(1H, s), 7.68(2H, d, J=8.4Hz), 7.57(2H, d, J=8.4Hz), 7.43(1H, s), 7.27(4H, m), 5.47(2H, s) and 4.17(2H, s) ppm. EXAMPLE 16 l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)-4- methylimidazole hydrochloride salt Step A: 4-Iodo-5-methylimidazole To a solution of 4-methyl imidazole(8.20g, 100 mmol) and sodium carbonate (21.2g, 200 mmol) in water (650 mL) was added a solution of sodium iodide (26.5g, 180 mmol) and iodine (25.4g, 100 mmol) in water (350 mL) over 90 minutes at room temperature. The reaction was stirred a furthur 30 minutes and filtered. The resulting white solid was washed with water and dried in vacuo at 50°C. IH NMR (CD3OD 400MHz) d 7.57 (IH, s) 4.86(1H, brs) and 2.20(3H, s) ppm. Step B: l-Trityl-4-iodo-5-methylimidazole To a cold (0°C) solution of 4-iodo-5-methylimidazole (5.0g, 24.0 mmol) and triethylamine (5.0 mL, 36.0 mmol) in CH2CI2 ( 100 mL) and 1 ,4-dioxane (50 mL) was added trityl chloride (8.0g, 29.0 mmol). The resultant mixture was stirred for 2 hours and quenched with ice and extracted with diethyl ether. The organic extracts were washed with sat. aq. NaHC03, dried (K2CO3) and the solvent evaporated in vacuo. The product mixture was concentrated onto silica gel and chromatographed (Silica gel, 30-50% EtOAc in hexanes) to afford the title compound as a pale yellow powder. IH NMR (CDCI3, 400MHz) δ 7.43(1H, s), 7.35-7.30 (9H, m), 7.25-7.10 (6H, m) and 2.27(3H, s) ppm. Step C: l -Trityl-4-(4-cyanobenzyl)5-methylimidazole To a suspension of activated zinc dust (0.262g, 3.99 mmol) in THF (1 mL) was added dibromoethane (0.035 mL, 0.039 mmol) and the reaction stirred under argon at 20°C for 45 minutes. The suspension was cooled to 0°C and a-bromo-p-tolunitrile (0.5 lg, 2.60 mmol) in THF (3 mL) was added dropwise over a period of 10 minutes. The reaction was then allowed to stir at 20°C for 45 minutes and bis(triphenyl- phosphine)Nickel II chloride (0.130g, 0.399 mmol) and 5-iodo-l -trityl imidazole (15.95g, 36.6mmol) were added in one portion.The resulting mixture was stirred 3 hours at 20°C and then quenched by addition of saturated NH3 solution (2 mL) and the mixture stirred for 3 hours, extracted with EtOAc (2 x 25 mL), dried (MgSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 20% EtOAc in CH2CI2 to afford the title compound as a white solid. iH NMR (CD3OD, 400MHz) δ 7.62 (2H, d, J=8.3Hz), 7.40-7.34(9H, m), 7.31(2H, d, J=8.3Hz), 7.26(1H, s), 7.18-7.10(6H, m), 3.93(2H, s), and 1.41 (3H, s) ppm. Step D: 1 -(2'-Trifluoromethyl-4-biphenylmethy l)-5-(4- cyanobenzyl)-4-methylimidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, step C using l -trityl-4-(4-cyanobenzyl)- 5 -methylimidazole .. Anal. Calcd. for C26H20N3F3 I .OO HCI C, 66.74 H, 4.52; N, 8.98. Found: C, 66.42; H, 4.42; N, 8.86. lH NMR (CD3OD 400MHz) δ 8.98(1H, s), 7.77(1H, d, J=7.8Hz), 7.66(1H, t, J=7.5Hz), 7.62-7.50(3H, m), 7.35-7.00( 7H, m), 5.37(2H, s), 4.20(2H, s) and 2.34(3H, s) ppm. EXAMPLE 17 l-(4-Biphenylmethyl)-5-(4-cyanophenyloxy)-imidazole Step A: 5-(4-Cyanophenyloxy imidazole Sodium metal (1.10 g, 47.8 mmol) was dissolved in anhydrous methanol and 4-cyanophenol (5.70 g, 47.8 mmol) was added. The resultant solution was concentrated and dried under vacuum overnight. A mixture of this sodium salt and 4-cyanophenol (25 g, mp 1 10-1 13°C) was heated to 125- 130°C and neat methyl N- (cyanomethyl)methanimidate (5.0 g, 51 mmol; Hosmane, R. S. et al, J. Org. Chem., 1212, 1984) was added dropwise over a period of 10 minutes under a slow stream of dry argon. The resultant mixture was stirred at 120°C for 2 hours, cooled, and the reaction product partitioned between methylene chloride (500 mL) and aqueous sodium hydroxide (1 M, 500 mL). The aqueous layer was separated and extracted with methylene chloride (3 x 100 mL). The organic extracts were combined, washed with brine (100 mL), dried (K2CO3), and the solvent evaporated in vacuo. The residue was purified by chroma¬ tography (Silica gel, 3:7 acetone in CHCI3) to afford the title compound as a white powder. i H NMR (DMSO-dό 400MHz) δ 7.79 (2H, d, J = 9.0 Hz), 7.54 ( I H, s), 7.11 (2H, d, J = 9.0 Hz) and 6.96 ( 1 H, s) ppm. Step B: 4-(4-Cvanophenyloxy)- 1 -trityl-imidazole To a cold (0°C) solution of 4-(4-cyanophenyloxy)- imidazole (155 mg, 0.84 mmol) and triethylamine (0.129 mL, 0.92 mmol) in DMF (1 mL) was added trityl chloride (245 mg, 0.88 mmol). The resultant mixture was stirred at ambient temperature for 5 days. The product mixture was concentrated onto silica gel, chromatographed (Silica gel, 1 :9 acetone in CHCI3) to afford the title compound as a white powder. i H NMR (CDCI3 400MHz) δ 7.57 (2H, d, J = 9.0 Hz), 7.38 (IH, s), 7.35-7.09 (16H, m), 7.08 (2H, d, J = 9.0 Hz) and 6.54(1 H, s) ppm. Step C: l -(4-Biphenylmethyl)-5-(4-cvanophenyloxy)-imidazole The title compound was prepared using the protocol described in example 5, step C using 4-biphenyl methanol and substituting 4-(4-cyanobenzyl)-l-trityl-imidazole with 4-(4- cyanophenyloxy)-l -trityl-imidazole. The title compound was purified by chromatography (Silica gel 3:7 acetone in CHCI3) and obtained as a white solid. Anal. Calcd for C23H17N3OO.35 H2O: C, 77.23; H, 4.99; N, 1 1.75. Found: C, 77.30; H, 4.95; N, 1 1.58. I H NMR (CDCI3, 400MHz) δ 7.80-7.35 (10 H, m), 7.16 (2H, d, J = 8.1 Hz), 7.01 (2H, d, J = 8.8 Hz), 6.74 (I H, s) and 4.98 (2H, s) ppm. Using the same procedure but substituting 4-(2-trifluoromethylphenyl)- benzylalcohol for biphenylmethanol in Step C the following compound was prepared: 1 -(4-(2-trifluoromethylphenyl)phenyl methyl)-5-(4-cyanophenyloxy)- imidazole Anal. Calcd for C24H16N3OF3O.3 H 0: C, 67.86; H, 3.94; N, 9.89. Found: C, 67.85; H, 3.84; N, 9.73. Using the same procedure but substituting 4-bromophenol for 4- cyanophenol in Step A the following compound was prepared: l -(4-Biphenylmethyl)-5-(4-bromophenyloxy)-imidazole Anal. Calcd for C22HπBrN2θ: C, 65.20; H, 4.23; N, 6.91. Found: C, 65.26; H, 4.33; N, 6.80. EXAMPLE 18 5-(4-Cyanophenyloxy)-l -(2'-methyl-4-biphenylmethyl)-imidazole hydrochloride salt The title compound was prepared using the protocol described in example 17, step C, substituting 4-biphenylmethanol with 2'-methyl-4-biphenylmethanol. The hydrochloride salt was obtained by treatment of a solution of the imidazole in acetonitrile with aq. HCI and evaporation of the solvents in vacuo. Anal. Calcd for C23H17N3O-0.58 H20-1.45 HCI: C, 67.23; H, 5.08; N, 9.80. Found: C, 67.30; H, 5.08; N, 9.74. IH NMR CDC13 δ 7.56 (2H, d, J = 6.9 Hz), 7.46 (IH, s), 7.26-7.10 (8H, m), 7.02 (2H, d, J = 8.8 Hz), 6.75 (IH, s), 4.99 (2H, s) and 2.19 (3H, s) ppm. EXAMPLE 19 5-(4-Biphenyloxy)-l -(4-cvanobenzyl)-imidazole trifluoroacetate salt Step A: 4-(4-Bromophenyloxy)imidazole The title compound was prepared as white solid using the protocol described in example 17 - step A, substituting 4-cyanophenol with 4-bromophenol, and performing the reaction at 100-1 10°C. iH NMR (DMSO-d6 400MHz) δ 7.49(1 H, s), 7.48(2H, d, J = 9.0 Hz), 6.93(2H, d, J = 9.0 Hz) and 6.85(1 H, s) ppm. Step B: 4-(4-Bromophenyloxy)- 1 -trityl-imidazole The title compound was prepared as white solid using the protocol described in example 17 - step B, using 4-(4-bromophenyloxy) imidazole. Step C: 5-(4-Bromophenyloxy)- 1 -(4-cyanobenzyl)-imidazole The title compound was prepared as a white solid using the protocol described in example 5, step C using 4-cyanobenzyl alcohol and 4-(4-bromophenyloxy)-l -trityl-imidazole. The title compound was purified by chromatography (Silica gel 3:7 acetone in CHCI3). i H NMR (CDCI3 400MHz) δ 7.61 (2H, d, J = 8.1 Hz), 7.38(2H, d, J = 9.0 Hz), 7.37(1 H, s), 7.21 (2H, d, J = 9.0 Hz), 6.63( 1H, s) and 5.03(2H, s) ppm. Step D: 5-(4-Biphenyloxy)- 1 -(4-cyanobenzyl)-imidazole trifluoroacetate salt A mixture of 5-(4-bromophenyloxy)-l-(4-cyanobenzyl)- imidazole (100 mg, 0.28 mmol), phenyl boronic acid (69 mg, 0.56 mmol), K3PO4 (240 mg, 1.13 mmol), and DMF (5 mL) was purged with dry argon for a period of 15 minutes. Tetrakis(triphenyl- phosphine)palladium(O) (33 mg, 0.028 mmol) was added, and the resultant solution was stirred at 80 °C for 18 hours. The solvents were evaporated in vacuo, and the residue partitioned between CH2CI2 and water. The aqueous extract was separated, and extracted with CH2CI2. The organic extracts were combined, dried (Na2S04, filtered and evaporated in vacuo. The residue was purified by chromatography (Silica gel, eluting with 3:7 acetone in CHCI3, and the trifluoroacate salt obtained by treatment of a solution of the imidazole in acetonitrile with aqueous TFA and evaporation of the solvents in vacuo. Anal. Calcd for C2 H 17N3θ» 1.25 TFA: C, 62.01 ; H, 3.72; N, 8.51. Found: C, 61.99; H, 3.69; N, 8.13. i H NMR (CDC13, 400MHz) δ 7.60(2H, d, J = 8.3 Hz), 7.54-7.32(8 H, m), 7.23(2H, d, J = 8.5 Hz), 7.00(2H, d, J = 8.8 Hz), 6.72( 1 H, s) and 5.06 (2H, s) ppm. EXAMPLE 20 5-(2'-Methyl-4-biphenoxy)- 1 -(4-cyanobenzyl)-imidazole trifluoroacetate salt The title compound was prepared as a white solid using the protocol described in example 19- step D, substituting phenyl boronic acid with o-tolylboronic acid, and stirring the reaction mixture at 100°C for 24 hours. Anal. Calcd for C24Hl9N3θ « 1.30 TFA-0.75 H 2 0: C, 60.72; H, 3.98; N, 7.99. Found: C, 60.77; H, 4.00; N, 7.76. IH NMR (CDCI3 400MHz) δ 7.61(2H, d, J = 8.5 Hz), 7.41 (1 H, s), 7.27-7.18(8 H, m), 6.98(2H, d, J = 8.8 Hz),6.70 (IH, s), 5.08(2H, s) and 2.25(3H, s) ppm. EXAMPLE 21 5-(4-(3',5'-dichloro)biphenylmethyl)- l -(4-cyanobenzyl)imidazole hydrochloride salt Step A: 4-(3 , .5'-Dichlorophenyl) benzyl alcohol The title compound was prepared using the protocol described in example 5, steps A-B using 3,5-dichloroiodobenzene. I H NMR (CDCI3, 400MHz) δ 7.54(2H, dt, J=8.20 and 2.0Hz), 7.48- 7.43(4H, m), 7.33(1H, t, J=2.0Hz), 4.76(2H, d, J=5.9Hz) and 1.68( 1 H, t, J=5.9Hz) ppm. Step B: 4-(3'.5'-Dichlorophenyl) benzyl bromide To a solution of triphenylphospine (636mg, 2.42 mmol) and carbon tetrabromide (830mg, 2.50 mmol) in diethyl ether (5 mL) was added a solution of 4-(3',5'-bis- chlorophenyl) benzyl alcohol (50mg, 1.98 mmol) in CH2CI2 (12 mL). The reaction was stirred at ambient temperature for 16 hours, silica gel was than added and the solvent evaporated in vacuo. The product was isolated by chroma- tography (Silica gel, 10-30% EtOAc in hexanes) and obtained as a white solid. I H NMR (CDCI3, 400MHz) δ 7.54-7.46(4H, m), 7.46-7.43(2H, m), 7.35(1 H, m) and 4.54(2H, s) ppm. Step C: 1 -Trityl-4-(4-(3'.5'-dichloro)-biphenylmethyl- imidazole To a suspension of activated zinc dust (0.080g, 1.22 mmol) in THF (0.25 mL) was added dibromoethane (0.01 1 mL, 0.122 mmol) and the reaction stirred under argon at 20°C for 45 minutes. 4-(3',5'- Dichlorophenyl) benzyl bromide (0.250g, 0.791 mmol) in THF ( 1 mL) was added dropwise over a period of 10 minutes. The reaction was then allowed to stir at 20°C for 45 minutes and bis(triphenylphosphine) Nickel II chloride (0..04g, 0.031 mmol) and 4-iodo-l -trityl-imidazole (15.95g, 36.6mmol) were added in one portion. The resulting mixture was stirred 16 hours at 20°C and then quenched by addition of sat. aq. NH4CI solution (2 mL) and the mixture stirred for 3 hours, extracted with EtOAc (2 x 25 mL), dried (MgSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 30-50% EtOAc in CH2CI2) to afford the title compound as a white solid. IH NMR (CDCl3, 400MHz) δ 7.50-7.28 (15H, m), 7.18-7.10(6H, m), 6.59(1H, s) and 3.93(2H, s) ppm. Step D: 5-(4-(3'.5'-Dichloro)-biphenylmethyl)- 1 -(4-cyanobenzyl) imidazole hydrochloride salt A suspension of 4-cyanobenzyl bromide ( 19.1mg, 0.097 mmol) and the trityl derivative from step C (52.5mg, 0.096 mmol) in acetonitrile (0.4 mL) was stirred at 55°C for 16 hours. The solvent was evaporated in vacuo and the residue dissolved in methanol (4 mL) and stirred at reflux for 1 hour. The solvent was evaporated in vacuo and partitioned between EtOAc and sat. aq. NaHCθ3, the organic layer was dried, (Na2Sθ4) and evaporated in vacuo. The residue was chroma- tograped (Silica gel, 2% MeOH in CH2CI2), to afford the imidazole, which was dissolved in acetonitrile and converted to the HCI salt by addition of 1 equivalent of IM HCI. Evaporation of the solvent in vacuo afforded the title compound as a white solid. IH NMR (CD3OD 400MHZ) δ 8.97(1H, s), 7.63(2H, d, J=8.2Hz), 7.53(2H, s), 7.48(2H, d, J=8.2Hz), 7.42(2H, s), 7.21 (2H, d, J=8.0Hz), 7.18(2H, d, J=8.2Hz), 5.49(2H, s) and 4.07(2H, s) ppm. EXAMPLE 22 1 -(4-biphenylmethyl)-5-( 1 -(R,S)-acetoxy- 1 -(4- cyanophenyDmethylimidazole hydrochloride salt Step A: 1 -Trityl-4-(l -(R,S)-hydroxy- 1 -(4-cyanophenyl) methylimidazole To a solution of l-trityl-4-iodoimidazolel (lOg, 23 mmol) in CH2CI2 (93 mL) at room temperature was added ethyl magnesium bromide (8.4 mL of a 3M solution in diethyl ether) and the reaction stirred for 2 hours. 4-Cyanobenzaldehyde (3.36g, 25.21 mmol) was added and the reaction stirred a furthur 16 hours. The reaction was quenched with sat. aq. NH4CI and stirred until homogeneous. The pH was adjusted to 8.5 with sat. aq. NaHC03 and extracted with CH2CI2. The combined organic extracts were washed with brine, dried (MgSθ4) and the solvent evaporated in vacuo. The resulting white solid was suspended in EtOAc (200 mL) and collected by filtration. IH NMR (CDCI3, 400MHZ) δ 7.60(2H, d, J=8.2Hz), 7.52(2H, d, J=8.2Hz), 7.41 (1 H, d, J=1.4Hz), 7.38-7.20(9H, m), 7.15-7.02(6H, m), 6.62(1H, s), 5.79(1H, d, J=4.6Hz), and 3.1 1 ( 1 H, d, J=4.6Hz) ppm. 1 Journal of Organic Chemistry 56, 5739, 1991 Step B: 1 -Trityl-4-( 1 -(R,S)-acetoxy- 1 -(4-cyanophenyl) methylimidazole A solution of l -trityl-4-(l -(R,S)-hydroxy-l -(4- cyanophenyl)methylimidazole (2.00g, 4.53 mmol), pyridine (1.10 mL) and acetic anhydride (0.641 mL) in DMF (20 mL) at room temperature was stirred for 16 hours. The reaction was quenched with sat. aq. NaHCθ3 (50 mL) and water (50 mL), extracted with ethyl acetate dried, (MgSθ4) and the solvent evaporated in vacuo. The resulting solids were washed with diethylether to provide the title compound as an off white solid. H NMR (CDC13, 400MHz) δ 7.62(2H, d, J=8.4Hz), 7.53(2H, d, J=8.2Hz), 7.39(1 H, d, J= 1.3Hz), 7.38-7.28(9H, m), 7.15-7.02(6H, m), 6.78(2H, s) and 2.12(3H, s) ppm. Step C: l -(4-Biphenylmethyl)-5-(l-(R,S)-acetoxy- l -(4- cyanophenyPmethylimidazole hydrochloride salt The title compound was prepared using the protocol described in example 5, step C using l -trityl-4-(l -(R,S)-acetoxy- l-(4-cyanophenyl)methylimidazole and 4-biphenylmethanol. Anal. Calcd. for C26H21N3O2 I.OO HC1-0.55H2O C, 68.81 H, 5.13 N, 9.26. Found: C, 68.98; H, 5.22; N, 8.87. FAB MS 408(MH+) IH NMR (CD3OD 400MHz) δ 9.09(lH, s), 7.70(2H, d, J=8.4Hz), 7.61(4H, t, J=8.2Hz), 7.45(1H, s), 7.45( 4H, t, J=8.2Hz), 7.36(1H, t, J=7.3Hz), 7.23(2H, d, J=8.3Hz), 7.05(1 H, s), 5.54(2H, d, J=2.2Hz) andl .96(3H, s) ppm. EXAMPLE 23 1 -(4-Biphenylmethyl)-5-( 1 -(R,S)-hydroxy- 1 -(4-cyanophenyl) methylimidazole hydrochloride salt To a solution of l -(4-biphenylmethyl)-5-( l -(R,S)-acetoxy- l -(4-cyanophenyl)methylimidazole, from example 22, (389mg 0.955 mmol) in THF (5 mL) at 0°C was added lithium hydroxide (0.192 mL), 0.192 mmol)and the reaction stirred at room temperature for 3 hours. EtOAc (75 mL) and water (25 mL) were added and the organic layer separated, dried (MgSθ4) and the solvent evaporated in vacuo. The residue was purified by chromatography (Silica gel, 5% MeOH in CH2C12) and converted to the HCI salt by treatment with HCI in EtOAc and evaporation of the solvent in vacuo. Anal. Calcd. for C24H 19N3OO.7O HCI C, 73.73 H, 5.08 N, 10.75. Found: C, 73.76; H, 5.17; N, 10.58. IH NMR (CD3OD, 400MHz) δ 8.57(1H, s), 7.67(2H, d, J=8.4Hz), 7.63-7.56(4H, m), 7.51(2H, d, J=8.0Hz), 7.44( 2H, t, J=7.4Hz), 7.35(1 H, t, J=7.5Hz), 7.23(2H, d, J=8.2Hz), 7.05(1H, s), 5.94(1H, s), 5.50(1H, d, J=15.4Hz) and 5.45(1H, d, J=15.4Hz) ppm. EXAMPLE 24 1 -(4-Biphenylmethyl)-5-( 1 -(R,S)-amino- 1 -(4-cyanophenyl) methylimidazole hydrochloride salt A solution of l -(4-biphenylmethyl)-5-(l-(R,S)-hydroxy- l-(4-cyanophenyl)methylimidazole (49.0mg, 0.122 mmol) in thionyl chloride (5 mL) at room temperature was stirred for 45 minutes. The solvent was evaporated in vacuo and the residue was treated with 4M NH3 in MeOH and the solution stirred for 1 hour and the solvents evaporated in vacuo.The residue was purified by chromatography (Silica gel, 2-5% NH4OH in acetonitrile) and converted to the HCI salt by treatment with HCI in acetonitrile and evaporation of the solvent in vacuo. Anal. Calcd. for C24H20N4 2.35HC1 C, 64.04H, 5.00 N, 12.45. Found: C, 64.13; H, 4.98; N, 12.43. I H NMR (CD3OD 400MHz) δ 9.20(1H, s), 7.93(1 H, s), 7.64(2H, d, J=8.4Hz), 7.54(2H, d, J=7.3Hz), 7.48-7.40(4H, m), 7.36(3H, m), 7.09(2H, d, J=8.2Hz), 5.98(1H, s), 5.54( 1 H, d, J=14.9Hz) and 5.45( 1H, d, J=14.9Hz) ppm. EXAMPLE 25 1 -(4-biphenylmethyl)-5-( 1 -(R,S)-methoxy- 1 -(4-cyanophenyl)- methylimidazole The title compound was obtained as a minor component by the protocol described in example 24. IH NMR (CD3OD 400MHZ) δ 7.76(2H, d, J=8.2Hz), 7.75(1 H, s), 7.64(2H, d, J=7.6Hz), 7.58(2H, d, J=8.2Hz), 7.50-7.40(4H, m), 7.36(1H, t, J=7.5Hz), 7.13(2H, d, J=7.9Hz), 6.56(1H, s), 5.47(1H, s), 5.25(1H, d, J=15.4Hz), 5.20(1H, d, J=15.4Hz) and 3.17(3H, s) ppm. EXAMPLE 26 1 -(4-Cvanobenzyl)-5-. l-hvdroxy-l-(4-biphenyP-methyl imidazole Step A: l-Triphenylmethyl-4-(hydroxymethyl)imidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35.0 g, 260 mmol) in 250 mL of dry DMF 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 DMF (500 mL ) was added dropwise. The reaction mixture was stirred for 20 hours, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid which was sufficiently pure for use in the next step. Step B: l -Triphenylmethyl-4-(acetoxymethyl)imidazole Alcohol from Step A (260 mmol, prepared above) was suspended in 500 mL of pyridine. Acetic anhydride (74 mL, 780 mmol) was added dropwise, and the reaction was stirred for 48 hours during which it became homogeneous. The solution was poured into 2 L of EtOAc, washed with water (3 x 1 L), 5% aq. HCI (2 x 1 L), sat. aq. NaHCO .3 , and brine, and then dried, (Na2Sθ4) and concentrated in vacuo to provide the cmde product. The acetate was isolated as a white powder which was sufficiently pure for use in the next reaction. Step C: 1 -(4-Cyanobenzyl)-5-(acetoxymethy l)imidazole hydrobromide A solution of the product from Step B (85.8 g, 225 mmol) and a-bromo-p-tolunitrile (50.1 g, 232 mmol) in EtOAc (500 mL ) was stirred at 60°C for 20 hours, 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 concen¬ trated in vacuo to a volume 200 mL, heated at 60°C for two hours, cooled to room temperature, and filtered. The filtrate was concentrated in vacuo to a volume 100 mL, then heated at 60°C for two hours, cooled to room temperature, and concentrated in vacuo to provide a pale yellow solid. All of the solid material was combined, dissolved in methanol (500 mL), and warmed to 60 °C. After two hours, the solution was concentrated in vacuo to provide a white solid which was triturated with hexane to remove soluble materials. Evaporation of residual solvent 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-CvanobenzvI)-5-(hvdroxymethyl)imidazole To a solution of the acetate from Step C (50.4 g, 150 mmol) in 1.5 L of 3: 1 THF/water at 0°C was added lithium hydroxide monohydrate (18.9 g, 450 mmol). After one hour, the reaction was concentrated in vacuo, diluted with EtOAc (3 L), and washed with water, sat. aq. NaHCθ 3 and brine. The solution was then dried, (Na 2 Sθ4) filtered, and concentrated in vacuo to provide the cmde product as a pale yellow fluffy solid which was sufficiently pure for use in the next step without further purification. Step E: 1 -(4-Cyanobenzyl)-5 -imidazole carboxaldehyde To a solution of the alcohol from Step D (21.5 g, 101 mmol) in DMSO (500 mL) at room temperature was added triethyl- amine (56 mL, 402 mmol), then Sθ 3 -pyridine complex (40.5 g, 254 mmol). After 45 minutes, the reaction was poured into 2.5 L of EtOAc, washed with water (4 x 1 L) and brine, dried, (Na 2 S0 4 ), and concentrated in vacuo to provide the aldehyde as a white powder which was sufficiently pure for use in the next step without further purification. Step F: 1 -(4-Cyanobenzyl)-5-( 1 -hydroxy- 1 -(4-biphenyl)-methyl imidazole A Grignard reagent, freshly prepared from 4-bromo- biphenyl (116 mg, 0.500 mmol) and magnesium turnings ( 18 mg, 0.73 mmol) in dry THF (0.50 mL) was added to a dry Argon-purged 3mL flask containing the l-(4-cyanobenzyl)-5 -imidazole carboxaldehyde (105 mg, 0.50 mmol) in dry THF (0.2 mL) with vigorous stirring at room temperature. After 1 hour the reaction was quenched with sat. aq. NH 4 C1 (5 mL) and distributed between EtOAc (50 mL) and H 2 0 (50 mL). The organic phase was evaporated in vacuo and the residue chromatographed (Silica gel, 5% MeOH in CHCI 3 ) to afford the title compound. Anal. Calcd for C24H19N3OO. IO CHCI3O. IO CH3OH: C, 76.37 H, 5.16; N, 1 1.04. Found: C, 76.13; H, 5.10; N, 10.76. FAB MS 366 (MH+) EXAMPLE 27 1 -(4-Cyanobenzy P-5-( 1 -oxo- 1 -(4-bipheny l)-methy 1 imidazole The alcohol from example 26 (105 mg, 0.228 mmol) in dioxane (3 mL) and activated manganese dioxide (300 mg) and the mixture was stirred at reflux for 2 hours. The mixture was filtered and the clear filtrate was evaporated and the residue chromatographed (Silica gel, 3%MeOH in CHC1 3 ) to afford the title compound. Anal. Calcd for C24Hl7N3θ » 0.35 CHCI3: C, 72.17; H, 4.32; N, 10.37. Found: C, 71.87; H, 4.45; N, 10.29. EXAMPLE 28 l -(4-Cyanobenzyl)-5-(l -hydroxy- l-(3-fluoro-4-biphenyl)-methyl imidazole A Grignard reagent, freshly prepared from 4-bromo-2- fluorobiphenyl] (251 mg, 1 mmol) and magnesium turnings (36 mg, 1.45 mmol) in dry THF (1 mL) was added to a dry argon-purged 5mL flask containing l -(4-cyanobenzyl)-5-imidazole carboxaldehyde (212 mg, 1 mmol) in dry THF (0.40 mL) with vigorous stirring at room temperature. After 1 hour the reaction was quenched with sat. aq. NH4CI (10 mL) and distributed between EtOAc (100 mL) and H2O (50 mL). The organic phase was evaporated and the residue was chromatographed (Silica gel, 5% MeOH in CHC13) to afford the title compound. Anal. Calcd for C24HI8N3OFO.O5 CHCI3: C, 74.18; H, 4.67; N, 10.79. Found: C, 74.13; H, 4.97; N, 10.48. FAB MS 384(MH+) iH NMR (CDCI3, 400MHz) δ 5.25( 2H, d, J=3.6Hz), 5.78 (IH, s), 6.84 (IH, s), 7.04-7.13 (4H, m), 7.30-7.39(2H, m) and 7.45-7.55 (7H, m) ppm. EXAMPLE 29 1 -(4-Cvanobenzyl)-5-( 1 -hydroxy- 1 -(3-biphenyl)methyl-imidazole A Grignard reagent, freshly prepared from 3-biphenyl- bromide (116 mg, 0.50 mmol) and magnesium turnings (18 mg, 0.73 mmol) in dry THF (0.5 mL) was added to a dry Argon-purged 3 mL flask containing l -(4-cyanobenzyl)-5-imidazole carboxaldehyde (105 mg, 0.50 mmol) in dry THF (0.20 mL) with vigorous stirring at room temperature. After 1 hour the reaction was quenched with sat. NH4CI (5 mL) and distributed between EtOAc (50 mL) and H2O (50 mL). The organic phase was evaporated and the residue chromatographed (Silica gel, 5% MeOH in CHCI3) to afford the title compound. Anal. Calcd for C24Hl9N3θ«0.10 CHCl3:«0.15CH3OH: C, 75.34 H, 5.10; N, 10.87. Found: C, 75.25 H, 5.13; N, 10.48. FAB MS 366 (MH+) IH NMR (CDCI3, 400MHz) δ 5.23 (2H, d,J=3.6 Hz), 5.78 (IH, s), 6.81(1H, s), 7.02(2H, d, J=3.6Hz), 7.26 (2H, d, J=3.6Hz) 7.32-7.37(3H, m) and 7.39-7.52 (7H, m) ppm. EXAMPLE 30 5-(2-f 1 , 1 '-Biphenyl]viny lene)- 1 -(4-cyanobenzyl)imidazole trifluoroacetic acid salt A mixture of 4-biphenyl bromide (260 mg, 1.1 mmol), 5- vinyl-l -(4-cyanobenzyl)imidiazole (248 mg, 1 mmol), palladium (II) acetate (10 mg), tri-o-tolylphosphine (30 mg), triethylamine (500 mL) in DMF (1 mL) was heated at 95°C for 20 hours. The dark solution was cooled and chromatographed (Silica gel, 1 % MeOH in CHCI3) to yield cmde product which was furthur purified by preparative HPLC, (gradient elution, 95 :5 to 5:95% wateπacetonitrile containing 0.1 % trifluoroacetic acid) to afford the title compound as a white solid. Anal. Calcd. for C24H19N3- 1.40 C2HO2F3: C, 64.07; H, 3.95; N, 8.06. Found: C, 64.05; H, 3.99; N, 7.68. FAB MS 362 (MH+). EXAMPLE 31 l -[N-(l -(4-cyanobenzyl)-5-imidazolylmethyl)amino]-3-methoxy-4- phenylbenzene Step 1 : Preparation of l -triphenylmethyl-4-(hydroxymethyl)-imidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35 g) in 250 mL of dry DMF at room temperature was added triethylamine (90.6 mL). A white solid precipitated from the solution. Chlorotriphenylmethane (76.1 g) in 500 mL of DMF was added dropwise. The reaction mixture was stirred for 20 hours, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid which was sufficiently pure for use in the next step. Step 2: Preparation of l -triphenylmethyl-4-(acetoxymethyl)-imidazole The product from Step 1 was suspended in 500 mL of pyridine. Acetic anhydride (74 mL) was added dropwise, and the reaction was stirred for 48 hours during which it became homogeneous. The solution was poured into 2 L of EtOAc, washed with water (3 x 1 L), 5% aq. HCI soln. (2 x 1 L), sat. aq. NaHCθ 3 , and brine, then dried (Na2SO_ι), filtered, and concentrated in vacuo to provide the cmde product. The titled acetate product was isolated as a white powder (85.8 g) which was sufficiently pure for use in the next step. Step 3: Preparation of 1 -(4-cyanobenzyl)-5-(acetoxymethyl)imidazole hydrobromide A solution of the product from Step 2 (85.8 g) and -bromo- -tolunitrile (50.1 g) in 500 mL of EtOAc was stirred at 60°C for 20 hours, during which a pale yellow precipitate formed. The reaction was cooled to room 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 two hours, cooled to room temperature, and filtered again. The filtrate was concentrated in vacuo to a volume 100 mL, reheated at 60°C for another two hours, cooled to room temperature, and concentrated in vacuo to provide a pale yellow solid. All of the solid material was combined, dissolved in 500 mL of methanol, and warmed to 60°C. After two hours, the solution was reconcentrated in vacuo to provide a white solid which was triturated with hexane to remove soluble materials. Removal of residual solvents in vacuo provided the titled product hydrobromide as a white solid (50.4 g, 89% purity by HPLC) which was used in the next step without further purification. Step 4: Preparation of 1 -(4-cvanobenzyl)-5-(hvdroxymethyl)-imidazole To a solution of the acetate from Step 3 (50.4 g) in 1.5 L of 3: 1 THF/water at 0 °C was added lithium hydroxide monohydrate ( 18.9 g). After one hour, the reaction was concentrated in vacuo, diluted with EtOAc (3 L), and washed with water, sat. aq. NaHCθ and brine. The solution was then dried (Na 2 SO_ . ), filtered, and concentrated in vacuo to provide the cmde product (26.2 g) as a pale yellow fluffy solid which was sufficiently pure for use in the next step without further purification. Step 5: Preparation of 1 -(4-cyanobenzyl)-5-imidazole-carboxaldehvde To a solution of the alcohol from Step 4 (21.5 g) in 500 mL of DMSO at room temperature was added triethylamine (56 mL), then Sθ 3 -pyridine complex (40.5 g). After 45 minutes, the reaction was poured into 2.5 L of EtOAc, washed with water (4 x 1 L) and brine, dried (Na 2 Sθ 4 ), filtered, and concentrated in vacuo to provide the titled aldehyde (18.7 g) as a white powder which was sufficiently pure for use in the next step without further purification. Step 6: Preparation of l-[N-(l -(4-cyanobenzyl)-5- imidazolylmethyl)aminol-3-methoxy-4-phenylbenzene To a solution of l-amino-3-methoxy-4-phenylbenzene in 1 ,2-dichloroethane at 0 °C was added 4A powdered molecular sieves and sodium triacetoxyborohydride. l -(4-Cyanobenzyl)-5-imidazole- carboxaldehyde was added, followed by 5 drops of acetic acid. The cooling bath was removed after 5 hours, and the reaction was stirred for another 15 hours. The reaction was poured into ethyl acetate and water. The organic layer was extracted with sat. aq. NaHCθ 3 solution and brine, then dried (Na 2 Sθ 4 ) and concentrated in vacuo to provide the product. Analysis calculated for C 25 H 22 N 4 O: C, 73,38; H, 6.07; N, 12.53; Found: C, 73.36; H, 6.00; N, 12.49. EXAMPLE 32 1 -(3'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 3-iodotoluene. Anal. Calcd. for C25H 2 ιN 3 - 1.00 HC1-0.45 H 2 0: C, 73.75; H, 5.64; N, 10.32. Found: C, 73.69; H, 5.40; N, 10.39. FABMS 364 (MH + ) EXAMPLE 33 1 -(4'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 4-iodotoluene. Anal. Calcd. for C2.sH21N3- l .OO HC1 0.10 H 2 0: C, 74.75; H, 5.57; N, 10.46. Found: C, 74.79; H, 5.37; N, 10.09. FABMS 364 (MH + ) EXAMPLE 34 l -(3'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 3-trifluoromethyl iodobenzene. FABMS 418 (MH + ) EXAMPLE 35 l -(4'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 4-trifluoromethyl iodobenzene. Anal. Calcd. for C25H18N 3 F3O.95 HCI- 1.15 H 2 0: C, 58.97; H, 4.40; N, 8.25. Found: C, 58.92; H, 4.40; N, 8.43. FABMS 418 (MH + ) EXAMPLE 36 l -(3'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 3-chloroiodobenzene. Anal. Calcd. for C 2 5H 2 ιNv l .OO HC1 0.20 H2O: C, 68.00; H, 4.61 ; N, 9.91. Found: C, 67.95; H, 4.57; N, 10.30 FABMS 384 (MH + ) EXAMPLE 37 1 -(4'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 4-chloroiodobenzene. Anal. Calcd. for C25H21N3 I .OO HC1-0.90 H 2 0: C, 66.03; H, 4.80; N, 9.63. Found: C, 66.09; H, 4.75; N, 9.48 FABMS 384 (MH + ) EXAMPLE 38 1 -(2'3'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 2,3-dichloroiodobenzene. FABMS 418 (MH + ) EXAMPLE 39 1 -(2'4'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 2,4-dichloroiodobenzene. Anal. Calcd. for C 2 4Hι 7 N 3 Cl2- 1.00 HC1 0.30 H2O: C, 62.64; H, 4.07; N, 9.13. Found: C, 62.64; H, 4.23; N, 8.86 FABMS 418 (MH + ) EXAMPLE 40 l -(2'5'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, steps A-C using 2,5-dichloroiodobenzene. Anal. Calcd. for C_4Hi7N 3 Clr l .20 HCI-0.35 H 0: C, 61.55; H, 4.07; N, 8.97 Found: C, 61.53; H, 4.08; N, 9.03 FABMS 418 (MH + ) EXAMPLE 41 l -(3'-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrobromide salt The title compound was prepared using the protocol described in Example 13, steps A-C using 3-trifluoro iodobenzene. Anal. Calcd. for C 25 H 18 N 3 OF 3 - 1.00 HC1-: C, 63.91 ; H, 4.08; N, 8.94 Found: C, 63.77; H, 3.97; N, 8.60 FAB HRMS exact mass calcd for C 25 H 18 N 3 OF 3 434.147543 (MH+); found 434.148022. EXAMPLE 42 1 -(2'-Fluoro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrobromide salt The title compound was prepared using the protocol described in Example 13, steps A-C using 2-fluoro iodobenzene. Anal. Calcd. for C 2 4Hι_N 3 F- 1.20 HBr-0.15 H 2 0: C, 63.91 ; H, 4.31 ; N, 9.32 Found: C, 64.04; H, 4.12; N, 8.92 FABMS 368 (MH + ) EXAMPLE 43 l -(4-(2'-Trifluoromethylphenyl)-2-Chloropheny_me cyanobenzyl) imidazole hydrochloride salt The title compound was prepared using the protocol described in Example 13, steps A-C using 2-chloro-4-iodotoluene and 2-trifluoromethylbenzene boronic acid. Anal. Calcd. for C25Hι 7 N 3 F 3 Cl- 1.00 HC1 0.15 EtOAc: C, 61.31 ; H, 3.86; N, 8.38 Found: C, 61.33; H, 3.78; N, 8.15 FABMS 452 (MH + ) EXAMPLE 44 1 - { 1 -(4-(2'-trifluoromethylphenyl)pheny l)ethyl } -5-(4-cyanobenzy 1) imidazole hydrochloride salt Step A: 4-(2 > -trifluoromethylphenyl)benzaldehvde To a solution of 4-formylbenzeneboronic acid (4.00 g, 26.7 mmol) and Na2C03 (5.66 g, 53.4 mmol) in water (240 mL) was added p-dioxane (240 mL). This mixture was treated sequentially with 2-iodobenzotrifluoride (3.74 mL, 26.7 mmol) and palladium (II) acetate (540 mg, 2.40 mmol) and allowed to stir at ambient temperature for 24 hours. The solvent was evaporated in vacuo. To the residue was added EtOAc (400 mL) and water (300 mL). The aqueous layer was acidified to pH 2 with 1.0 N aq. HCI and the layers separated. The aqueous layer was extracted with EtOAc (2 x 200 mL). The organic extracts were combined, washed with brine (200 mL), 5% aq. Na2S2θ3 (200 mL), saturated NaCl (200 mL), dried (Na2S04), and the solvent evaporated in vacuo and the residue chromatographed (Silica gel, 20-50% CH 2 C1 2 in hexanes) to afford the title compound. iH NMR (CDC13, 400MHz) δ 10.09(1H, s), 7.93(2H, d, J=8.0Hz), 7.78(1H, d, J=8.2Hz), 7.60(1 H, t, J=7.5Hz), 7.55-7.45(3H, m) and 7.33(1H, d, J=8.0Hz) ppm. Step B: l -(4-(2'-trifluoromethylphenyπphenyl)ethanol To a solution of 4-(2-trifluoromethylphenyl)- benzaldehyde (1.00 g, 0.40 mmol) in Et 2 0 (20 mL) at -70°C was added methyl lithium (2.85mL of a 1.4 M in Et 2 0 0.40 mmol) over 10 minutes. The reaction was allowed to warm to ambient temperature and stirred for 1 hour. The reaction was quenched by dropwise addition of sat. aq. NH 4 OH and extracted with Et 2 0 The organic layer was washed with brine and dried(MgS04), and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 20-50% CH 2 C1 2 in hexanes) to afford the title compound. I H NMR (CDCI3, 400MHZ) δ 7.75(1H, d, J=7.7Hz), ), 7.55(1H, t, J=7.4Hz), 7.47(1H, t, J=7.4Hz), 7.41 (2H, d, J=7.9Hz), 7.36-7.28(3H, m) and 4.98( 1 H, m) ppm. Step C: 1 - { 1 -(4-(2'-trifluoromethylphenyl)phenyl)ethy 1 } -5-(4- cyanobenzyPimidazole hydrochloride salt The title compound was prepared using the protocol described in Example 5, step C using the alcohol from step B. Anal. Calcd. for C 2 6H 2 oN 3 F3- 1.00 HCl-0.1 EtOAc: C, 66.52; H, 4.61; N, 8.81. Found: C, 66.74; H, 4.52; N, 8.98. EXAMPLE 45 l -(2'-Trifluoromethyl-4-biphenylpropyl)-5-(4-cyanobenzyl) imidazole . [23 Step A: E-Ethyl -3-(4-(2'-trifluoromethylphenyl)phenyl)prop-2- enoate To a solution of 4-(2'-trifluoromethylphenyl) benzaldehyde ( l .OOg, 3.996 mmol, prepared using the protocol described in Example 44, step A) in CH 2 C1 2 (8.0 mL) was added (carbethoxymethylene) triphenylphosphorane ( 1.46g, 4.196 mmol)and the reaction was stirred at room temperature for 16 hours. The solvent was evaporated in vacuo and the residue chromatographed (Silica gel, 2.5% EtOAc in hexanes) to afford the title compound. IH NMR (CD3OD 400MHz) δ 7.90-7.50(6H,m), ), 7.40 7.35(3H,m), 6.60(lH,d, J=16.1Hz), 4.27(2H, q, J=7.1 Hz), 1.34(3H, t, J=7.1 Hz),)ppm. Step B: Ethyl-3-(4-(2'-trifluoromethylphenyl)phenyl)- propionoate A solution of E-Ethyl -3-(4-(2'-trifluoromethylphenyl) phenyl)prop-2-enoate (0.444g, 1.388 mmol) and 10% palladium on carbon (0.044g) in EtOH (13.88 mL) was hydrogenated in a parr apparatus. The catalyst was removed by filtration through celite and thetitle compound obtained by solvent evaporation in vacuo. IH NMR (CD3OD 400MHz) δ 7.73(1 H, d, J=7.7Hz), 7.58(1H, t, J=7.7Hz), 7.48(1H, t, J=7.7Hz), 7.29(1H, d, J=7.7Hz), 7.24 (2H, d, J=8.2Hz), 7.19(2H, d, J=8.2Hz), 4.10(2H, q, J=7.1Hz), 2.96(2H, t, J=7.7Hz), 2.65(2H, t, J=7.5Hz) and 1.20(2H, qn, J=7.5Hz) ppm. Step C: 1 -(2'-Trifluoromethyl-4-biphenylpropyl)-5-(4- cyanobenzyl) imidazole The title compound was prepared using the protocol described in Example 5, steps B-C using the product from step B. IH NMR (CD3OD 400MHz) δ 7.75(lH, d, J=7.7Hz), 7.70- 7.60(3H, m), 7.52(1H, t, J=7.5Hz), 7.33(1H, d, J=7.9Hz), 7.21 ( IH, d, J=7.6Hz), 7.13 (2H, d, J=8.1 Hz), 6.78(1H, s), 4.03(2H, q, J=7.1Hz), 3.86 (2H, t, J=7.5Hz), 2.60(2H, t, J=7.5Hz) and 1.92(2H, qn, J=7.5Hz) ppm. EXAMPLE 46 l -(2'-N-t-Butoxycarbonylamino-4-biphenylmethyl)-5-(4- cvanobenzyl imidazole Step A: 4-(2 , -Cyanophenyl)benzoic acid methyl ester. To a solution of 2-bromobenzonitrile ( l .OOg, 5.494 mmol), in THF (16.5 mL) at - 100°C was added t-butyl lithium (6.46mL, of a 1.7M solution in pentane, 10.98 mmol. After 5 minutes zinc chloride(5.494 mL, of a I M solution in THF, 5.494 mmol) was added. The reaction was stirred for 10 minutes at -78°C and then allowed to warm to 0°C and stirred for 1 hour. This solution was added via cannula to a solution of methyl-4- iodobenzoate (1.44g, 5.494 mmol) and bis(triphenylphosphine) Nickel II chloride (0.359g, 0.549 mmol) in THF (12 mL). The reaction stirred for 1 hour at 0°C and then at ambient temperature for a furthur 16 hours. Saturated ammonium hydroxide solution (5 mL) was added and the mixture stirred until homogenous, extracted with EtOAc and the organic extracts washed with saturated brine, dried (MgS0 4 ) and evaporated in vacuo. The residue was chromatographed (Silica gel, 50% CH 2 C1 2 to 50% EtOAc in hexanes) to afford the title compound. I H NMR (CD3OD, 400MHz) δ 8.15(2H, d, J=8.7Hz), ),7.87(1 H, d, J=7.7Hz), 7.77(1H, t, J=7.5Hz), ), 7.69(2H, d, J=8.7Hz), 7.65- 7.55(2H, m), and 3.95(3H, s) ppm. Step B: 4-(2 , -Aminomethylphenyl)hvdroxymethylbenzene To a solution of 4-(2'-cyanophenyl)benzoic acid methyl ester (0.428g, 1.804 mmol) in tetrahydrofuran (14.3 mL) at 0°C was added 1.0 M lithium aluminum hydride in tetrahydrofuran (3.61 mL, 3.61 mmol) over 10 minutes. The reaction was allowed to stir at ambient temperature for 3 hours, then warmed to 45 °C for 3 hours, cooled and quenched by dropwise addition of saturated Na 2 S0 4 (0.46 mL). The reaction was diluted with diethylether, Na 2 S0 4 was added, the mixture filtered through a pad of Celite and the filtrate evaporated in vacuo to afford the title compound. IH NMR (CD3OD, 400MHz) δ 7.47(1 H, d, J=7.5Hz), 7.42(2H, d, J=8.4Hz), 7.40-7.15 (4H,m), 4.66(2H,s) and 3.73(2H,s) ppm. Step C: 4-(2'-t-Butoxycarbonylaminomethylphenyl) hydroxymethylbenzene To a solution of 4-(2'-aminomethylphenyl) hydroxy¬ methylbenzene (0.374g, 1.754 mmol) and triethylamine (0.269mL, 1.929 mmol) in DMF (8.0 mL) at 0°C was added t-butylcarbonate (0.383g, 1.754 mmol) in DMF (2.0 mL) over 10 minutes. The reaction was allowed to stir at ambient temperature for 16 hours. The reaction was diluted with EtOAc, washed with 10% aq. citric acid, and then sat. aq. NaHC0 3 and dried(Na 2 S0 4 ). The solvent was evaporated in vacuo and the residue chromatographed (Silica gel, EtOAc) to afford the title compound. I H NMR (CD3OD, 400MHz) δ 7.50-7.15(8H, m), 4.66(2H,s), 4.15(2H,s) and 1.43(9H,s) ppm Step D: 1 -(2'-N-t-Butoxycarbonylaminomethyl-4- biphenylmethyl)-5-(4-cyanobenzyl) imidazole The title compound was prepared using the protocol described in Example 5, step C using the product from step C. FAB HRMS exact mass calcd for C oH nN 4 0 2 479.244702 (MH+); found 479.244189. Anal. Calcd. for C30H30N4 O, 0.10 H.O: C, 75.29; H, 6.32; N, 1 1.71. Found: C, 75.20; H, 5.87; N, 1 1.27. EXAMPLE 47 1 -(2 -Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt A solution of l -(2'-N-t-Butoxycarbonylaminomethyl- 4-biphenylmethyl) -5-(4-cyanobenzyl) imidazole (43.7mg, 0.094 mmol) in EtOAc (lOmL) was saturated with HCI gas. After 10 minutes the solvent was evaporated in vacuo to afford the title compound as a white solid. FAB HRMS exact mass calcd for C25H22N4 379.192272 (MH+); found 379.192525. Anal. Calcd. for C25H22N4O.75 HCI: C, 62.71 ; H, 5.21 ; N, 1 1.70. Found: C, 62.71 ; H, 5.14; N, 1 1.32. EXAMPLE 48 l -(2'-Acetylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole To a solution of l-(2'-aminomethyl-4-biphenylmethyl)- 5 -(4-cyanobenzyl) imidazole hyrochloride (0.107g, 0.237 mmol) and triethylamine (0.033mL, 0.237 mmol) in CH 2 C1 2 (4.7 mL) at 0°C was added acetic anhydride (0.383g, 1.754 mmol). The reaction was allowed to stir at ambient temperature for 16 hours. The reaction was diluted with CH 2 C1 2 , washed sat. aq. Na 2 C0 3 and dried (Na 2 S0 4 ). The solvent was evaporated in vacuo and the residue chromatographed (Silica gel, 3% MeOH in CH 2 C1 2 ) to afford the free base which was converted to the HCI salt.. FAB HRMS exact mass calcd for C25H22N4O 421.202837 (MH+); found 421.203621. Anal. Calcd. for C25H22N4O 1.60 HCI: C, 67.72; H, 5.39; N, 1 1.70. Found: C, 67.58; H, 5.21 ; N, 1 1.77. EXAMPLE 49 l -(2'-Methylsulfonylaminomethyl-4-biphenylmethyl)-5-(4- cyanobenzyl) imidazole hydrochloride The title compound was prepared using the protocol described in Example 48, using methanesulfonyl chloride. FAB HRMS exact mass calcd for C26H 2 4N 4 0 2 S 457.169823 (MH+); found 457.170937. Anal. Calcd. for C 2 6H24N 0 2 S 1.70 HCI 0.20 EtOAc: C, 60.03; H, 5.13; N, 10.45. Found: C, 59.99; H, 4.93; N, 10.15. EXAMPLE 49 l -(2'-Ethylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride To a solution of l-(2'-aminomethyl-4-biphenylmethyl)- 5-(4-cyanobenzyl) imidazole hyrochloride (0.1 OOg, 0.222 mmol) acetaldehyde (0.024mL, 0.444 mmol) and 4A molecular sieves (300mg) in MeOH (0.44 mL) at room temperature was added triethylamine to a pH of 7. Sodium cyanoborohydride (0.028g, 0.444 mmol) was added and the reaction was stirred for 16 hours.. The reaction was filtered through celite and the filtrate evaporated in vacuo. The residue was partitioned between CH 2 C1 2 , and sat. aq. Na 2 C0 3 and the organic layer separated and dried (Na 2 S0 4 ). The solvent was evaporated in vacuo and the residue chromatographed (Silica gel, 3% NH 4 OH in Acetonitrile) to afford the free base which was converted to the HCI salt.. FAB HRMS exact mass calcd for C 27 H 2 βN 4 407.223572 (MH+); found 421.223572. EXAMPLE 50 l -(2'-Phenylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride To a slurry of l -(2'-aminomethyl-4-biphenylrnethyl)- 5-(4-cyanobenzyl) imidazole hyrochloride (0.097g, 0.216 mmol) triphenyl bismuth (0.166g, 0.377 mmol) and copperll acetate (0.059g, 0.323 mmol) in CH 2 C1 2 (0.43 mL) at room temperature was added triethylamine (0.045mL, 0.323 mmol) and the reaction was stirred for 16 hours.. Silica gel was added and the solvent evaporated in vacuo.The solid was applied to a column and chromatographed (Silica gel, 2% MeOH in CH 2 C1 2 ) to afford the free base which was converted to the HCI salt.. FAB HRMS exact mass calcd for C31H2 N 454.215747 (MH+); found 454212863. EXAMPLE 51 l -(2'-Glycinylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride To a slurry of l-(2'-aminomethyl-4-biphenylmethyl)- 5-(4-cyanobenzyl) imidazole hyrochloride (0.1 OOg, 0.222 mmol) N-Boc glycine (0.039g, 0.222 mmol), triethylamine (0.093mL, 0.666 mmol) and HOBT (0.030g, 0.222 mmol) in CH 2 C1 2 (2.2 mL) at room temperature was added EDC (0.042g, 0.222 mmol) and the reaction was stirred for 16 hours.. The reaction was diluted with CH 2 C1 2 and washed with NaHC0 3 and the organic extracts dried (Na 2 S0 4 ) and evaporated in vacuo. The residue was chroma¬ tographed (Silica gel, 2.5-5% MeOH in CH 2 C1 2 ) to afford the N-Boc glycinyl derivative. This material was dissolved in EtOAc (3mL) and saturated with HCI gas. The reaction was stirred for 40 minutes at 0°C and the solvent evaporated to afford the title compound as a white solid FABMS 436(MH + ) C27H25N5O Anal. Calcd. for C27H25N5O 1.55 HCI 2.70 H 2 0: C, 60.06; H, 5.96; N, 12.97. Found: C, 60.04; H, 5.96; N, 12.93. EXAMPLE 52 1 -(2'-Methyl-4-biphenylmethyl)-2-chloro-5-(4-cyanobenzyl) imidazole and l-(2'-Methyl-4-biphenylmethyl)- 4-chloro 5-(4- cyanobenzyl) imidazole A solution of l-(4-(4'-Methylbiphenylmethyl)-5-(4- cyanobenzyl)imidazole (120mg, 0.330 mmol) in CH 2 CI 2 was treated with NCS (44mg, 0.330 mmol) and the reaction stirred for 16 hours at room temperature. The solvent was evaporated in vacuo and the residue chromatographed (Silica gel, 2% MeOH in CH 2 C1 2 ) to afford a mixture of regioisomers. These were separated by preparative HPLC to afford the title compounds. l -(2'-Methyl-4-biphenylmethyl)-2-chloro-5-(4-cyanobenzyl) imidazole iH NMR (CD3OD, 400MHz) δ 7.54(1 H, d, J=8.2Hz), 7.27(2H, d, J=8.4Hz), 7.25-7.10 (7H, m), 6.93(2H, d, J=8.4Hz), 6.85(1H, s), 5.21 (2H, s), 4.05(2H, s) and 2.20(3H, s)ppm. l -(2'-Methyl-4-biphenylmethyl)-4-chloro 5-(4-cyanobenzyl) imidazole I H NMR (CD3OD, 400MHz) δ 7.79(1 H, s), 7.50(1H, d, J=8.2Hz), 7.25-7.02 (9H, m), 7.00(2H, d, J=8.4Hz), 5.15(2H, s), 4.05(2H, s) and 2.16(3H, s)ppm. EXAMPLE 53 l -(3'-Chloro-2-methyl-4-biphenylmethyl)-4-(4-cyanobenzy imidazole hydrochloride salt Step A: Preparation of 4-trifluoromethylsulfonylyoxy-3- methylbenzaldehyde To a solution of 4-hydroxy-3-methylbenzaldehyde (Aldrich; (1 g; 7.34 mmol) in 20 mL of CH2CI 2 at room temper- ature was added triethylamine (1.13 mL, 8.08 mmol), then triflic anhydride (1.36 mL, 8.08 mmol). After 2 h, the reaction was poured into CH 2 CI 2 , washed with saturated NaHCθ 3 , then brine, dried, filtered, and concentrated in vacuo to provide the crude aldehyde. Column chromatography (silica gel; hexane:EtOAc 4: 1 ) afforded the title compound as an oil. Step B: Preparation of (3'-chlorophenyl)-3-methylbenzaldehyde Following the procedure described for Example 13, step A, but using the product from step A above and 3-chlorobenzene- boronic acid as starting materials the title product was obtained. Step C: Preparation of (3'-chlorophenyl)-3-methylbenzylalcohoI Following the procedure described for Example 7, step B, but using the product from step B above as starting material, the title product was obtained. 13 : Step D: Preparation of l -(3'-chloro-2-methyl-4- biphenylmethyl)-4-(4-cyanobenzyl)imidazole hydrochloride salt Using the alcohol from step C and following the procedure described for Example 5, step C with a subsequent purification by silica gel chromatography (EtOAc then 2% MeOH in CHCI 3 ). The first eluted material afforded the title compound after treatment with HCI and Et2θ. Analysis calculated for C 2 H 2 oN 3 Cl«2.7HCl«0.3Et 2 0: C, 60.67; H, 4.99; N, 8.10; Found: C, 60.67; H, 4.62; N, 7.95. EXAMPLE 54 l -(3'-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt Following the precedure of Example 53, step D, but collecting the later eluting material the title compound was obtained. Analysis calculated for C 2 _.H 20 N 3 Cl-l .7HClO.2E. 2 O: C, 65.27; H, 5.03; N, 8.85; Found: C, 65.36; H, 5.03; N, 8.86. EXAMPLE 55 1 -(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-4-(4- cyanobenzyl) imidazole hydrochloride salt Following the procedure described for Example 53, steps B-C but using 3-trifluoromethylbenzeneboronic acid as starting materials, the title compound was obtained. It was isolated by silica gel chromatography (EtOAc then 2% MeOH in CHCI 3 ) collecting the first eluted material and then subsequent treatment with HCI and Et 2 0. Analysis calculated for C26H2oN 3 F -1.4HCl-0.35EtOAc: C, 64.10; H, 4.75; N, 8.18; Found: C, 64.14; H, 4.50; N, 8.10. EXAMPLE 56 1 -(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole trifluoroacetic acid salt Following the procedure described for Example 53, steps B-C but using 3-trifluoromethylbenzeneboronic acid as starting materials, the title compound was obtained. It was isolated by silica gel chromatography (EtOAc then 2% MeOH in CHCI 3 ) collecting the second eluted material and then subsequent preparative HPLC purification. Analysis calculated for C 26 H 20 N 3 F 3 -l .35TFA-O.4H 2 O: C, 58.17; H, 3.77; N, 7.09; Found: C, 58.17; H, 3.78; N, 7.19. EXAMPLE 57 l -(3'-Methoxy-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzvPimidazole hydrochloride salt Step A: Preparation of 2-bromo-5-hydroxymethyltoluene To a solution of 4-bromo-3-methylbenzoic acid (Aldrich; (3 g, 14 mmol) in 75 mL of THF at 0°C was added BH 3 .THF complex (IM in THF; 15 mL, 15 mmol). After stirring for 3 h at room temperature, 10 mL IN NaOH was added slowly. The solution was poured into water and extracted with CHCI 3 , washed with water then brine, dried and evaporated. Column chromatography of the product (silica gel; EtOAc) afforded the title compound as a solid. Step B: Preparation of 4-(3'-methoxyphenyl)-3-methyl- benzylalcohol Following the procedure described for Example 13, step A, but using the product from step A above and 3-methoxybenzene- boronic acid as starting materials the title product was obtained. Step C: Preparation of 1 -(3'-methoxy-2-methyl-4- biphenylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt Following the procedure described for Example 5, step C, but using the product from step B above as starting material, the title product was obtained. Analysis calculated for C 26 H 2 N .3 O-l.2HCl: C, 71.41 ; H, 5.58; N, 9.61 ; Found: C, 71.34; H, 5.45; N, 9.83. EXAMPLE 58 l -(2'-Chloro-4'-fluoro-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt Step A: Preparation of l -chloro-5-fluoro-2-trifluoromethyl- sulfonylyoxybenzene Following the procedure described for Example A, step A, but using 2-chloro-4-fluorophenoI as starting materials the title product was obtained. Step B: Preparation of l-(2'-Chloro-4'-fluoro-4-biphenylmethyl)- 5-(4-cyanobenzyl)imidazole hydrochloride salt Following the procedure described for Example 5, steps A-C, but using the product from step A above as starting material, the title product was obtained. Analysis calculated for C 2 4H 17 N 3 OC.F-l .lHCl: C, 65.22; H, 4.13; N, 9.51 ; Found: C, 65.33; H, 4.27; N, 9.24. EXAMPLE 59 l -(2'-Ethyl-4-biphenylmethyI)-5-(4-cyanobenzyl)imidazole trifluoroacetic acid salt Following the procedure described for Example 5, steps A-C, but using 1 -iodo-2-ethylbenzene as starting material, the title product was obtained. Analysis calculated for C2 6 H 23 N 3 -l .35TFA-l .4H 2 O: C, 61.93; H, 4.92; N, 7.55; Found: C, 61.96; H, 5.12; N, 7.16. EXAMPLE 60 l-(2'-(2-Propyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole trifluoroacetic acid salt Following the procedure described for Example 5, steps A-C, but using 1 -iodo-2-(2-propyl)benzene as starting material, the title product was obtained. Analysis calculated for C 27 H 25 N 3 -1.5TFA-0.75H 2 O: C, 62.55; H, 4.90; N, 7.29; Found: C, 62.56; H, 4.95; N, 6.98. EXAMPLE 61 1 -(2'-(2-Methyl-2-propyl)-4-biphenylmethyl)-5-(4- cyanobenzv imidazole hydrochloride salt Step A: Preparation of 2-(2-methyl-2-propyl)- l -trifluoromethyl- sulfonylyoxybenzene Following the procedure described for Example 53, step A, but using 2-(2-methyl-2-propyl)phenol as starting materials the title product was obtained. Step B: Preparation of l -(2'-(2-methyl-2-propyl)-4-biphenyl- methyP-5-(4-cyanobenzyPimidazole hydrochloride salt Following the procedure described for Example 5, steps A-C, but using the product from step A above as starting material, the title product was obtained. Analysis calculated for C_ 8 H 27 N 3 *1.75HC1: C, 71.64; H, 6.17; N, 8.95; Found: C, 71.71 ; H, 5.93; N, 8.56. EXAMPLE 62 l -(2'-Ethyl-4-biphenylmethyl)-5-(4-(l/ -tetrazol-5-yl))benzyl)imidazole trifluoroacetic acid salt l -(2'-Ethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole (from Example 59; 150 mg, 0.4 mmol) was dissolved in toluene (10 mL) and treated with trimethylsilylazide (0.15 mL, 1.08 mmol) and dibutyltin oxide (1 10 mg, 0.44 mmol). The mixture was heated at 100°C for 16 h, cooled and the solvent removed in vacuo. Chromatography of the residue (silica gel; EtOH: NH 4 OH: H 2 O 20:1 :1) gave an oil which was further purified by preparative HPLC to give the title compound. FAB mass spectmm (M+H) = 421.08 Analysis calculated for C 2 6H24N 6 -1.35TFA-0.15H 2 O: C, 59.72; H, 4.48; N, 14.56; Found: C, 59.71; H, 4.42; N, 14.54. EXAMPLE 63 l -[ l-(4-Cyanobenzyl)imidazol-5-ylmethoxy]-4-(2'-methylphenyl)-2- (3-N-phthalimido- l -propyl)benzene trifluoroacetic acid salt Step A: Preparation of 4-(2 , -methylphenyl)phenol Following the procedure described for Example 5, step A, but 4-bromophenol 2-methylbenzeneboronic acid as starting materials the title product was obtained Step B: Preparation of l -allyloxy-4-(2 , -methylphenyPbenzene The phenol from step A (1.72 g, 9.35 mmol), Cs 2 C0 3 (3.6 g, 10.5 mmol) and allylbromide (0.9 mL, 10.3 mmol) in DMF (47 nmL) were stirred at room temperaΦre for 48 h. The mixture was poured into water and extracted with EtOAc, washed with water (3x), brine, dried and evaporated to give the title compound as an oil. Step C: Preparation of 2-allyl-4-(2-methylphenyl)phenol To a stirred solution of BCI 3 (I M in p-xylene; 6.7 mL, 6.7 mmol) in chlorobenzene at -15°C was added the allyl ether from step B (1.48 g, 6.6 mmol) in 5 mL of chlorobenzene. After lh at - 15°C, the mixture was poured into ice/MeOH, extracted with E.2O (3x), washed with saturated NaHCθ 3 , water then brine. The dried solution was evaporated to give the title compound as an oil. Step D: Preparation of 2-aIlyl- l -benzyloxy-4-(2- methylphenyPbenzene Following the procedure of step B but using benzyl bromide, the phenol from step C was converted into the title compound Step E: Preparation of l -benzyloxy-2-(3-hydroxypropyl)-4-(2'- methylphenvPbenzene To a stirred solution of the allyl derivative from step D, (3.2 g, 10.2 mmol) in THF (40 mL) at 0°C was added 9-BBN (0.5 M in THF; 30.6 mL, 15 mmol) and the mixture stirred for 4 h. The solution was treated with 30 H 2 θ 2 lN NaOH and after 15 minutes, poured into water, and extracted with EtOAc (2x). The organic layers were washed with water, brine, dried and evaporated to give an oil. Chromatography on silica gel (hexane/EtOAc 4: 1 ) afforded the title compound as an oil. Step F: Preparation of l -benzyloxy-2-(3-N-phthalimido-l -propyl)- 4-(2 , -methylphenyl)benzene To a stirred solution of the alcohol from step E, (1.5 g, 4.52 mmol) and triphenylphosphine (1.78 g, 5.65 mmol) in THF (30 mL) at room temperature was added dropwise a solution of DEAD (0.9 mL, 5.65 mmol) and phthalimide (731 mg, 5 mmol) in THF (5 mL). After stirring for 16 h, the mixture was concentrated in vacuo and the residue taken up in EtOAc. The solution was washed with 10% citric acid solution, saturated NaHCθ 3 , water then brine, dried and evaporated to give an oil. Column chromatography (silica gel; hexane:EtOAc 9: 1 ) afforded the title compound as an oil. Step G: Preparation of 2-(3-N-phthalimido- l -propyl)-4-(2'- methylphenvPphenol To a degassed solution of the benzylether from step F, ( 1.5 g, 3.3 mmol) in EtOH (30 mL) and EtOAc (5 mL) was added 300 μL of HO Ac and 10% palladium hydroxide on carbon (150 mg) and this was then placed on a Parr hydrogenation apparatus at 50 psi of hydrogen. After shaking for 24 h, the mixture was filtered through celite, the solvent removed and the residue chromatographed (silica gel; hexane:EtOAc 3: 1 ) to give the title compound as an oil. Step H: Preparation of l-(4-cyanobenzyl)-5-chloromethylimidazole hydrochloride A suspension of l -(4-cyanobenzyl)-5-hydroxy- methylimidazole (Example 26, step D; 3.1 g, 14.5 mmol) in thionyl chloride (20 mL) was heated at 60°C for 18 h. The excess thionyl chloride was removed in vacuo and the residue was azeotroped with CHCI 3 (3x) to give the title compound. Step I: Preparation of l -f l -(4-cyanobenzyl)imidazol-5-ylmethoxyJ- 4-(2'-methylphenyl)-2-(3-N-phthalimido-l-propyl)benzene trifluoroacetic acid salt Following the procedure described for step B, but using the phenol from step G and 5-chloromethyl-l -(4-cyanobenzyl) imidazole hydrochloride from step H as starting materials, the title compound was obtained. FAB mass spectrum (M+H) = 567.10. Analysis calculated for C 3 6H 30 N4O 3 -l .5TFA- l .OH2O: C, 61.98; H, 4.47; N, 7.41 ; Found: C, 61.91 ; H, 4.46; N, 7.31. EXAMPLE 64 l -(3',5'-Ditrifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt Following the procedure described for Example 5, steps A-C, but using 4-bromo-3-methylbenzoic acid and 3,5-ditrifluoro- methylbenzeneboronic acid as starting materials, the title product was obtained. Analysis calculated for C 27 Hι 9 N 3 -1.0HCl-0.25H 2 O: C, 60.00; H, 3.82; N, 7.78; Found: C, 59.91 ; H, 3.74; N, 7.75. EXAMPLE 65 1 -(3',5 '-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole hydrochloride salt Following the procedure described for Example 5, steps A-C, but using 4-bromo-3-methylbenzoic acid and 3,5-dichloro- benzeneboronic acid as starting materials, the title product was obtained. Analysis calculated for C 25 H. 9 N 3 Cl 2 -1.0HCl-1.5H 2 O: C, 60.56; H, 4.68; N, 8.47; Found: C, 60.40; H, 4.83; N, 8.23. EXAMPLE 66 l - '^'-Dimethyl^-memyl^-biphenylmethyO-S-^- cyanobenzyPimidazole hydrochloride salt Following the procedure described for Example 5, steps A-C, but using 4-bromo-3-methylbenzoic acid and 3,5- dimethylbenzeneboronic acid as starting materials, the title product was obtained. Analysis calculated for C2 7 H 25 N 3 -1.0HC1: C, 75.77; H, 6.12; N, 9.82; Found: C, 75.66; H, 6.10; N, 9.71. EXAMPLE 67 l -(3-(N-Boc-aminomethyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)- imidazole Step A: Preparation of 4-hydroxymethyl-biphenyl-3-carbaldehyde To a solution of 4-biphenylmethanol (0.368 g, 2 mmol) in ether (25 mL) and TMEDA (1.21 mL, 8 mmol) at 0°C was added n-butyllithium (2.5N hexanes; 3.2 mL, 8 mmol). The solution was then heated at reflux for lh, cooled to -60°C and CuCN (0.2 g, 2.2 mmol) added. After 30 minutes, the solution was cooled to -78°C and N-formylpiperidine (1.1 1 mL, 10 mmol) was then added drop- wise and stirring was continued for 1 h. The mixture was then warmed to -10°C, quenched with saturated NH 4 CI, extracted with ether washed withbrine, dried and the solvent removed in vacuo. Chromatography of the residue (silica gel; hexane:EtOAc 4: 1 ) afforded the title compound as a colorless oil. Step B: Preparation of 4-hydroxymethyl-biphenyI-3- carbaldehyde O -methyl -oxime A solution of the aldehyde from step A (0.13 g, 0.61 mmol), methoxylamine hydrochloride (61 mg, 0.735 mmol) and pyridine (2 mL) in EtOH (10 mL) was heated at reflux for 16 h. Further portions of methoxylamine hydrochloride (61 mg, 0.735 mmol) and pyridine (2 mL) were added and heating was continued for 24 h. The solution was cooled, diluted with EtOAc, extracted with water (2x) then brine, dried and concentrated to give the title compound as an oil. This was used as such in the next step. Step C: Preparation of 3-aminomethyl-biphenyl-4-methanol To a solution of the oxime from step B (0.51 g, 2.1 mmol) in THF (15 mL) at 0°C was added BH 3 .THF ( I M in hexane; 8 mL, 8 mmol) and the resulting solution was stirred at room temperature for 16 h then heated to reflux for 24 h. The solution was cooled to 0°C and IN NaOH (10 mL) was added slowly. After 1 h, the mixture was diluted with water, extracted withEtOAc (3x), washed with brine, dried and evaporated to give the title compound as an oil. This was used as such in the next step. Step D: Preparation of 3-N-Boc-aminomethyl-biphenyl-4-methanol To a solution of the amine from step C (0.39 g, 1.8 mmol) and Et 3 N (0.255 mL, 1.8 mmol) in DMF (10 mL) was added Boc-anhydride (0.4 g, 1.8 mmol) and the mixture was stirred for 16 h. The solution was diluted with water, extracted with EtOAc (3x) and the combined organic layers were then extracted with saturated NaHC0 3 then brine, dried and evaporated. Chromatography of the residue (silica gel; hexane:EtOAc 3: 1) afforded the title compound as a solid. Step F: Preparation of 3-(N-Boc-aminomethyl)-4-biphenylmethyl bromide A solution of the alcohol from step D (0.157 g, 0.5 mmol), triphenylphosphine (0.191 g, 0.75 mmol) and CBr4 (0.249 g, 0.75 mmol) in THF (15 mL) was stirred at room temperature for 16 h. The solvent was removed in vacuo and EtOAc was added to the residue. Filtration removed the insoluble material and the EtOAc solution was washed with water then brine, dried and evaporated. Purification of the residue on silica gel, eluting with hexane:EtOAc 12: 1 , afforded the title compound. Step G: Preparation l-(3-(N-Boc-am omethyl)-4-biphenylmethyl)- 5-(4-cyanobenzyl)imidazole Following the procedure of Example 1 , step B but using the bromide from step G as starting material, the title compound was obtained as a solid. Fab mass spectrum (M+H) = 479.12 Analysis calculated for C 3 oH 3 N 4 θ 2 -0.05CHCl 3 : C, 74.41 ; H, 5.67; N, 1 1.38; Found: C, 74.48; H, 6.25; N, 1 1.56. EXAMPLE 68 l -(3-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole dihydrochloride salt l -(3-(N-Boc-aminomethyl)-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole from Example 67 was dissolved in EtOAc 0°C and treated with HCI gas. The solvent was removed to give the title compound. Fab mass spectrum (M+H) = 379.16 EXAMPLE 69 l -(4-Cyanobenzyl)-2-methyl-5-(2'-methylbiphenyl-4-yloxy)imidazole trifluoroacetate salt Step A: Methyl N-(cvanomethyPethanimidate Finely grounded aminoacetonitrile hydrochloride (21 g) was stirred in a solution of chloroform (200 mL) saturated with ammonia gas for 10-15 minutes. The slurry was filtered through a plug of Celite. The filtrate was concentrated, and the residue distilled (36-40°C, 0.1 mmHg) to provide aminoacetonitrile as clear, colorless oil. Aminoacetonitrile (14 g) was added at a rate of 1 mL/min to a boiling mixture of trimethyl orthoacetate (200 mL), concentrated sulfuric acid (5 drops), and anhydrous sodium sulfate (20 g), with removal of distillate. The resultant mixture was heated for additional 30 minutes, filtered through Celite, and concentrated. The residue was distilled (50-60°C, 0.1 mmHg) to provide methyl N- (cyanomethyl)ethanimidate as clear, colorless oil. The ethanimidate was stored under dry argon at - 10°C. 1 H NMR (CDC13 300MHz) δ 4.1 1 (2H, s), 3.66 (3H, s), 1.97 (3H, s) ppm. Step B: 5-(4-Bromophenyloxy)-2-methylimidazole Using procedure described for the preparation of 5-(4- cyanophenyloxy)imidazole in Example 17, Step A, but substituting 4-bromophenol for 4-cyanophenol, methyl N-(cyanomethyl) ethanimidate for methyl N-(cyanomethyl)methanimidate, and after heating the resultant mixture at 100 °C for 4 hours, 5-(4-bromo- phenyloxy)-2-methylimidazole was prepared: iH NMR (DMSO-dό 300MHz) δ 7.45 (2H, d, J = 8.8 Hz), 6.93 (2H, d, J = 8.8 Hz), 6.91 (IH, s) and 2.22 (3H, s) ppm. Step C: 5-(4-Bromophenyloxy)-l-(4-cyanobenzyl)-2- methylimidazole To a cold (-78 °C) solution of 5-(4-bromophenyloxy)-2- methylimidazole (2.06 g, 8.14 mmol) in THF (30 mL), a solution of MeLi in diethyl ether (1.4 M, 8.96 mmol) was added. The resultant mixture was stirred at -78°C for 1 hour, and a solution of 4-cyano¬ benzyl bromide (1.68 g, 8.55 mmol) in THF (3 mL) was added. The mixΦre was allowed to warm up to room temperature, stirred overnight, and concentrated under vacuum. The residue was partitioned between water and a 9: 1 mixture of methylene chloride and methanol. The organic extract was washed with brine, dried (anhydrous sodium sulfate), filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a mixture of chloroform and acetone (8:2 v/v). Two alkylation products were isolated. iH NMR NOE experiments indicated that the major product to be 5-(4-bromophenyloxy)-3-(4- cyanobenzyl)-2-methylimidazole, and the minor product to be desired 5-(4-bromophenyl-oxy)- 1 -(4-cyanobenzyl)-2- methylimidazole. i H NMR (minor isomer; CDCI3 300MHz) δ 7.62 (2H, d, J = 8.8 Hz), 7.39 (2H, d, J = 9.0 Hz), 7.16 (2H, d, J = 8.8 Hz), 6.89 (2H, d, J = 9.0 Hz), 6.54 (IH, s), 4.98 (2H, s), and 2.30 (3H, s) ppm. Step D: 1 -(4-Cyanobenzyl)-2-methyl-5-(2'-methylbiphenyl-4- yloxyVimidazole trifluoroacetate salt The title compound was prepared as a white solid using the protocol described in Example 19 - Step D, substituting 5-(4- bromo-phenyloxy)-l-(4-cyanobenzyl)imidazole with 5-(4- bromophenyl-oxy)- 1 -(4-cyanobenzyl)-2-methylimidazole, phenyl boronic acid with o-tolylboronic acid, and stirring the reaction mixture at 100 °C for 18 hours. Anal. Calcd for C25H21N3O-1.10 TFA-0.95 H 2 0: C, 62.59; H, 4.63; N, 8.05. Found: C, 62.61 ; H, 4.66; N, 7.75. i H NMR (CDC13 300MHz) δ 6.68 (IH, s), 5.04 (2H, s), 2.31 (3H, s), and 2.23 (3H, s) ppm. EXAMPLE 70 5-(4-Cyanobeι zyl)-l-(3-cyano-2'-trifluoromethylbiphenyl-4-ylmethyl)- imidazole hydrochloride salt Step A: 3-Cyano-4-methyl-2 , -trifluoromethylbiphenyl The title compound was prepared as a white solid using the protocol described in Example 19 - Step D, substituting 5- (4-bromophenyloxy)- 1 -(4-cyanobenzyl)imidazole with 2-methyl-5- iodobenzonitrile, phenyl boronic acid with o-trifluoromethylboronic acid, and stirring the reaction mixture at 100°C for 18 hours. iH NMR (CDC13 300MHz) δ 7.8 - 7.2 (7H, m) and 2.61 (3H, s) ppm. Step B: 4-Bromomethyl-3-cyano-2'-trifluoromethylbiphenyl A mixture of 3-cyano-4-methyl-2'-trifluoromethyl- biphenyl (420 mg, 1.61 mmol), N-bromosuccinimide (286 mg, 1.61 mmol), AIBN ( 10 mg), and carbon tetrachloride (20 mL) was refluxed for 1 hour. The resultant mixture was concentrated, and the residue subjected to column chromatography on silica gel eluting with a mixture of ethyl acetate in hexane (7.5 to 92.5 v/v). Collection and concentration of appropriate fractions provided the title compound. i H NMR (CDC13 300MHz) δ 7.8 - 7.2 (7H, m) and 4.69 (2H, s) ppm. Step C: 5-(4-Cyanobenzyl)- 1 -(3-cyano-2'- trifluoromethvlbiphenyl-4-ylmethyP-imidazole hydrochloride salt The title compound was prepared as a white solid using the protocol described in Example 1 - Step B, substituting 4-chloromethyl-biphenyl with 4-bromomethyl-3-cyano-2'- trifluoromethy lbipheny 1. Anal. Calcd for C26H17N4 F3-1.50 HC1-1.45 H 2 0: C, 59.68; H, 4.12; N, 10.71. Found: C, 59.74; H, 4.12; N, 10.53. EXAMPLE 71 2-Amino-5-(biphenyl-4-ylmethyP- 1 -(4-cyanobenzvPimidazole Step A: N-Methoxy-N-methyl 2-(N-tert- butyloxycarbonylamino)-2-(biphenyl-4- ylmethvPacetamide To a cold (0°C) solution of N-Boc 4-biphenylalanine (2.5 g, 7.33 mmol) and N-methylmorpholine (0.96 mL, 8.79 mmol) in ethyl acetate (20 mL), isobutyl chloroformate (1.04 mL, 8.06 mmol) was added. The resultant mixture was stirred at 0°C for 30 min. N,N-Dimethyl-hydroxyamine hydrochloride (0.86 g, 8.79 mmol) and N-methyl-morpholine (0.96 mL, 8.79 mmol) was added, and the resultant mixture was stirred at room temp, overnight. The product mixture was diluted with ethyl acetate (100 mL). The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. 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 white solid. i H NMR (CDCI3 300MHz) δ 7.6 - 7.2 (9H, m), 5.2 (I H, br s), 5.0 ( IH, br s), 3.69 (3H, s), 3.19 (3H, s), 3.0 (2H, m), and 1.39 (9H, s). Step B: N-Methoxy-N-methyl 2-( (N-tert-butyloxycarbonyl)-(N- 4-bromobenzvPaminol-2-(biphenyl-4-ylmethyl)acetamide To a cold (-78°C) solution of N-methoxy-N-methyl 2- (N-tert-butyloxycarbonylamino)-2-(biphenyl-4-ylmethyl)acetamide (2.25 g, 5.86 mmol) in THF (60 mL), a solution of sodium bis(trimethylsilyl)amide in THF (1 M, 6.44 mL, 6.44 mmol) was added. The resulting mixture was stirred at -78°C for 1 hour. A solution of 4-bromobenzyl bromide (1.61 g) in THF (5 mL) was added, and the resultant mixture was allowed to warm up to room temp, and stirred overnight. The product mixture was diluted with diethyl ether. The organic extract was washed with brine, dried over 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: 2-A_mino-5-(biphenyl-4-ylmethyl)- 1 -(4-bromobenzyl)- imidazole To a cold (-40°C) slurry of LiAlH4 in anhydrous diethyl ether (50 mL), a solution of N-Methoxy-N-methyl 2-[(N- tert-butyloxy-carbonyl)-(N-4-bromobenzyl)aminol-2-(biphenyl-4- ylmethyl)acetamide (2.1 1 g, 3.82 mmol) in THF (10 mL) was added. The resultant mixture was stirred at -40 °C for 10 min. and allowed to warm up to 0°C. The mixture was then cooled back to -40°C, and quenched with aqueous KHSO4 solution with temperature of the mixture maintained below -30 °C. The resultant mixture was diluted with diethyl ether and stirred at room temp for 30 min. The ethereal solution was isolated, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide a foamy product. Without further purification, 0.6 g of the aldehyde obtained from the above procedure was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (2 mL) at room temperature for 15 min. The resulting mixture was concentrated under vacuum. The residue was dissolved in a mixture of absolute ethanol and dichloromethane (8 mL, 5: 1 v/v; pH adjusted to about 4 -5 with addition of diisopropylethylamine), treated with cyanamide (0.16 g, 3.69 mmol), and heated under reflux for 3 h. The resultant mixture was concentrated, and the residue subjected to column chromatography on silica gel eluting with a 1 : 1 mixture of 5% methanol in chloroform and chloroform saΦrated with ammonia gas. Collection and concentration of appropriate fractions provided the title aminoimidazole as white solid. iH NMR (CDC13 300MHz) δ 7.6-7.1 (1 IH, m), 6.79 (2H, d, J = 8.5 Hz), 6.59 (IH, s), 4.73 (2H, s), 3.81 (2H, s), and 3.72 (2H, br s) ppm. FAB MS 418/420 (MH+) Step D: 2- Amino-5-(bipheny 1-4-ylmethyl)- 1 -(4- cy anobenzy 1 )imi dazo le A mixΦre of 2-amino-5-(biphenyl-4-ylmethyl)-l - (4-bromo-benzyl)imidazole (1 14 mg, 0.27 mmol), anhydrous zinc cyanide (19 mg, 0.16 mmol), and anhydrous dimethylformamide (2 mL) was purged with argon for 20 minutes. Tetrakis(triphenyl- phosphine)palladium(O) (32 mg, 0.028 mmol) was added, and the resultant solution was stirred under argon at 80 °C for 36 hours. The product mixΦre was concentrated under vacuum, and the residue subjected to column chromatography on silica gel eluting with a 1 : 1 mixture of 10% methanol in chloroform and chloroform saturated with ammonia gas. Collection and concentration of appropriate fractions provided the title aminoimidazole as white solid. Anal. Calcd for C24H2θN4 « 0.10 CHCI3: C, 76.91 ; H, 5.38; N, 14.89. Found: C, 77.04; H, 5.47; N, 14.78. EXAMPLE 72 2- Amino- 1 -(biphenyl-4-ylmethyl)-5-(4-cyanobenzyl)imidazole trifluoroacetate salt Step A: N-Methoxy-N-methyl 2-(N-tert-butyloxycarbonylamino)-2- (4-bromobenzy Pacetami de The title compound was prepared as a white solid using the protocol described in Example 71 - Step A, substituting N-Boc 4-biphenyl-alanine with N-Boc 4-bromophenylalanine. iH NMR (CDCI3 300MHz) δ 7.39 (2H, J 8.5 Hz, d), 7.04 (2H, J 8.5 Hz, d), 5.2 (IH, br s), 4.9 (IH, br s), 3.69 (3H, s), 3.17 (3H, s), 2.9 (2H, m), and 1.39 (9H, s). Step B: N-Methoxy-N-methyl 2-[(N-tert-butyloxycarbonyl)-(N- biphenyl-4-ylmethyPamino1-2-(4-bromobenzyl)acetamide The title compound was prepared as a white solid using the protocol described in Example 71 - Step B, substituting N-methoxy-N-methyl 2-(N-tert-butyloxycarbonylamino)-2- (biphenyl-4-ylmethyl)-acetamide with N-Methoxy-N-methyl 2- (N-tert-butyloxycarbonylamino)-2-(4-bromobenzyl)acetamide, and 4-bromobenzyl bromide with biphenyl-4-ylmethyl iodide. Step C: 2- Amino- 1 -(biphenyl-4-ylmethyl)-5-(4-bromobenzyl)- imidazole The title compound was prepared as a white solid using the protocol described in Example 71 - Step C, substituting N-Methoxy-N-methyl 2-[(N-tert-butyloxy-carbonyl)-(N-4- bromobenzyl)amino]-2-(biphenyl-4-ylmethyl)acetamide with N-Methoxy-N-methyl 2-[(N-tert-butyloxycarbonyl)-(N-biphenyl- 4-ylmethyl)amino]-2-(4-bromobenzyl)-acetamide. iH NMR (CDC13 300MHz) δ 7.6-7.3 (8 H, m), 7.04 - 6.97 (4 H, m), 6.53 (IH, s), 4.78 (2H, s), 3.83 (2H, br s), and 3.76 (2H, s) ppm. FAB MS 418/420 (MH+) Step D: 2-Amino- l -(biphenyl-4-ylmethyl)-5-(4-cyanobenzyl)- imidazole trifluoroacetate salt The title compound was prepared as a white solid using the protocol described in Example 71 - Step D, substituting 2-Amino-5-(biphenyl-4-ylmethyl)- 1 -(4-bromobenzyl)imidazole with 2-amino- 1 -(biphenyl-4-ylmethy l)-5-(4-bromobenzyl)imidazole. Anal. Calcd for C24H2θN4 « 1.25 TFA: C, 62.78; H, 4.22; N, 1 1.05. Found: C, 62.93; H, 4.04; N, 10.68. EXAMPLE 73 l -(3-Butylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole hydrochloride Step A: (N-fgrf-butyP-4-biphenylcarboxamide To a 1L round bottomed flask with a stirring bar and a drying tube was added 4-biphenylbenzoic acid (35.14g, 177.26 mmol), CH 2 C1 2 (500 mL) and oxalyl chloride ( 17.18 mL, 196,96 mmol). To this well stirred mixture was added 10 drops of DMF. This mixture was stirred at ambient temperature for 5h. The solvent and excess oxalyl chloride were removed in vacuo and the solid acid chloride was redissolved in fresh CH 2 C1 2 (500 mL). This solution was cooled to 0 n C and ferf-butylamine (23.28 mL, 221.58 mmol), Et 3 N (30.88 mL, 221.58 mmol) and 4-DMAP (0.20g) were added sequentially. The cooling bath was allowed to expire and the mixture was stirred at ambient temperature for 18h. The reaction mixΦre was diluted with an equal volume of CHC1 and this solution was washed successively with IN HCI, NaHC0 3 solution and brine. Drying (MgS0 4 ), filtration and removal of the solvent in vacuo gave an off white solid. This material was triturated with Et 2 0 (100 mL) and collected on a frit and dried in vacuo to afford the title compound. *H NMR (CDC1 3 ) δ 1.49 (9H,s), 5.98 (IH, br s), 7.38 ( IH, m), 7.45 (2H, t, j=6 Hz), 7.62 (4H, m), 7.80 (2H, d, j=7 Hz). Step B: (N-__r -butyl)-3-( 1 -hydroxybuty lyl)-4- biphenylcarboxamide To three necked, 500 mL, oven dried round bottomed flask with a stirring bar, argon inlet, low temperaΦre thermometer and a septum was added (N-ferf-butyl)-4-biphenylcarboxamide (5.00g, 19.66 mmol) and dry THF (200 mL). This solution was cooled to -78°C and n-butyllithium (16.12 mL of a 2.5M solution in hexane, 40.30 mmol) was added with a syringe at dropwise so that the temperature did not exceed -65°C. The cooling bath was replaced with an ice-H 2 0 bath and the reaction was allowed to warm to 0°C and stir 45 min. The solution was recooled to -78°C and butyraldehyde (1.80 mL, 20.00 mmol) was added with a syringe. This mixture was warmed to 5°C during which time the mixture became homogenous. The mixture was poured into 10% aqueous citric acid and extracted with EtOAc. The organic fraction was washed with aqueous NaHC0 3 solution and brine. Drying (MgS0 4 ), filtration and removal of the solvent in vacuo gave a colorless foam. This material was chromatographed on silica gel using 15% EtOAc in hexane as eluant to afford the title compound. Η NMR (CDC1 3 ) δ 0.95 (3H, t, j=7.5 Hz), 1.36 (IH, m), 1.49 (9H, s), 1.50 (IH, m), 1.79 (I H, m), 1.95 (IH, m), 4.58 (I H, m), 4.75 ( I H, q, j=7 Hz), 6.00 (IH, br s), 7.38 ( IH, m), 7.47 (4H, m), 7.59 (3H, m). Step C: (N-ferf-butyl)-3-butyl-4-biphenylcarboxamide To 500 mL Parr flask was added (N-ferf-butyl)-3- (l -hydroxybutyl)-4-biphenylcarboxamide (3.50 g, 10.75 mmol), abs EtOH (125 mL) and 10% palladium on carbon (3.50g). This mixture was hyrogenolyzed at 60 psig and ambient temperature for 48h. The catalyst was removed by filtration on a celite pad anfd the solvent was removed in vacuo. This material was chromatographed on silica gel using 10% EtOAc in hexane as eluant to afford the title compound as a white crystalline solid. Η NMR (CDC1 3 ) δ 0.94 (3H, t, j=7.5 Hz), 1.39 (2H, m), 1.48 (9H, s), 1.63 (2H, m), 2.83 (2H, m), 5.60 (IH, br s), 7.38 (IH, m), 7.47 (4H, m), 7.59 (3H, m). Step D: 2-Chloroethyl 3-butyl-4-phenylbenzoate To a 200 mL round bottomed flask with a strirring bar and a reflux condenser was added (N-fe; f-butyl)-3-butyl-4- biphenylcarboxamide (3.17g, 10.24 mmol), ethylene glycol (25 mL) and 12N HCI (25 mL). This mixture was heated at reflux 72h. The cooled mixture was extracted with EtOAc and the EtOAc extracts were combined, washed with H 2 0 (3X) and brine. Drying (MgS0 4 ), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on silica gel using 30% EtOAc in hexane as eluantto afford the title compound as an oil. *H NMR (CDC1 3 ) δ 0.95 (3H, T, J= 6.4 Hz), 1.41 (2H, m), 1.65 (2H, m), 3.04 (2H, dd, j= 5.6, 1.0 Hz), 3.82 (2H, t, j=5.6 Hz), 4.58 (2H, t, j= 5.6), 7.38 (IH, m), 7.47 (3H, m), 7.62 (2H, m), 8.02 ( IH, d, j=8.9 Hz). Step E: 2-Butyl-4-phenyIbenzenemethanol To a 100 mL round bottomed flask with a stirring bar and an argon inlet was added 2-chloroethyl 3-butyl-4-phenylbenzoate (570 mg, 1.80 mmol), THF (9 mL) and LiBH 4 (9 mL of a 2M solution in THF, 18 mmol). This mixture was heated at reflux for 18h. The cooled reaction mixture was treated with IN HCI and extracted with EtOAc. The combined EtOAc extracts were washed with H 2 0 and brine. Drying (MgS0 4 ), filtration and removal of the solvent in vacuo gave an oil. Ths material was chromatographed on silica gel using 20% EtOAc in hexane as eluant to afford the title compound as a crystalline solid. J H NMR (CDC1 3 ) δ 0.97 (3H, t, j= 7.3), 1.41 (2H, m), 1.59 (2H, m), 2.76 (2H, dd, j= 5.6, 1.0 Hz), 4.77 (2H, s), 7.35 (I H, m), 7.44 (5H, m), 7.58 (2H, m). Step F: 2-Butyl-4-phenylbenzenemethyl bromide To a 200 mL round bottomed flask with a stirring bar and an argon inlet was added NBS (675 mg, 3.8 mmol) in 25 ml CH2CI2. This solution was cooled to 0°C and was added methylsulfide (.33 ml, 4.55 mmol). The resulting suspension was cooled to -20°C and was added and solution of 2-butyl-4- phenylbenzenemethanol ( 608 mg, 2.53 mmol) in 15 ml CH2CI2. The reaction mixture was stirred at 0°C for 3 h. Poured the solution mixture in 200ml ice. separated the layers, CH2CI2 layer was washed with H20 and brine, dried (MgSθ4), filtration and remeved solvent in vacuo to afford the title product as an oil. H NMR (CDC1 3 ) δ 0.98 (t, 3H), 1.45 (m, 2H), 1.69 (m, 2H), 2.79 (m, 2H), 4.6 (s, 2H), 7.36 (m, IH), 7.43 (m, 4H), 7.58 (d, J=7.32, 2H). Step G: l-(3-Butylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)- imidazole hydrochloride To a 50 mL round bottomed flask with a stirring bar and an argon inlet was added 2-Butyl-4-phenylbenzenemethyl bromide (750 mg, 1.70 mmol), and 1 -trityl-4-(4-cyanobenzyl) imidazole (638 mg, 1.5mmol) in CH3CN (12 mL). The mixture was refluxed for 24 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (10 mL), heated at reflux for 4 hour, removal of solvent in vacuo. The residue was partitioned between EtOAc and sat. aq. NaHCθ3 solution. The organic layer was dried, (MgSθ4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 3% 2-propanol in CHC13). The amine was converted to the HCI salt by treatment with 4.0M HCI in 1 ,4 dioxane. Triturated with EtOAc to afford a white solid. i H NMR (DMSO-d6, 400MHz) δ 0.90(t, 3H), 1.28(m, 2H), 1.45(m, 2H), 2.42(m, 2H), 4.09(s, 2H), 5.14(s, 2H), 6.94(d, J=8.06Hz, IH), 7.26(m, IH), 7.40-7.49(m, 7H), 7.56(d, J=6.96Hz, 2H), 7.68(d, J=7.87Hz, 2H), 8.38(br, s IH). EXAMPLE 74 l -(3-Propylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole hydrochloride Title compound was prepared using the procedure described in Example 73 substituting propionaldehyde for butyraldehyde in step B. IH NMR (DMSO-d6, 400MHz) δ 0.91 (t, 3H), 1.46- 1.51 (m, 2H), 2.5(m, 2H), 4.16(s, 2H), 5.44(s, 3H), 6.69(d, J=7.6Hz, IH), 7.31 - 7.39(m, 4H), 7.44-7.48(m, 3H), 7.59-7.63(m, 3H), 7.69(d, J=8.05Hz, 2H), 9.05(br, s IH). EXAMPLE 75 1 -(4-Cyanobenzyl)-5-l(3-fluoro-4-biphenyl)methy 1 ] imidazole trifluoroacetate salt Step A: 1 -(4-Cyanobenzyl)-5-[ 1 -chloro-(3-fluoro-4- biphenyPmethyllimidazole The alcohol from Example 28 (380 mg. lmmol) was dissolved in thionyl chloride (500 μl) and the solution was stirred at room temperaΦre for 4 hours and then evaporated solution in vacuo to afford title compound. Step B: 1 -(4-Cyanobenzyl)-5-[(3-fluoro-4- biphenyPmethyllimidazole trifluoroacetate salt The chloride from step A was hydrogenolyzed in absolute ethanol (10 mL) over 10% Pd/C (50mg) in a Parr apparatus at 40 psi (initial) for 6 days. The catalyst was filtered off, washed well with EtOH and the solvent was evaporated. The residue was chromatographed (silica gel, 2-5% MeoH-CHC13) and further purified by preparative HPLC. (gradient elution, 95:5 to 5:95% H2O-CH3CN containing 0.1 % TFA) to afford the title compound as a very hygroscopic white solid. FAB MS 368.13 (MH+) Hi NMR (CD3OD, 400 MHz) δ 4.10 (2H,s) 5.54 (2H,s), 6.88 (H,dd, J=11.6 and 1.6 Hz), 6.97 (H,dd, J=l 1.6 and 1.6 Hz), 7.23 (2H,d, J=8.8 HZ), 7.30 (H,t, J=8Hz), 7.30-7.49 (5H,m), 7.52 (H, brs), 7.64 (2H,dd, J=6.4 and 1.6 Hz), 9.07 (H, brs)ppm. EXAMPLE 76 1 -(4-Biphenylmethyl)-4-(4-cyanobenzyl-2-methylimidazole trifluoroacetate salt Step A: l -Trityl-4-(4-cyanobenzyl)-2-methylimidazoIe The title compound was prepared using the protocol described in Example 16, Step C using l -trityl-4-iodo-2- methylimidazole. FAB MS 440.27 (MH+) H i NMR (CDCI3, 400 Mhz) δ 1.61 (3H,s), 3.87 (2H,s), 6.45 (H,s), 7.09-7.15 (5H,m), 7.3-7.36 (12H,m), 7.54 (2H,d, J=8 Hz) ppm. Step B: l -(4-Biphenylmethyl)-4-(4-cyanobenzyl-2- methylimidazole trifluoroacetate salt The title compound was prepared using the protocol described in Example 2 using the product from Step A above but purified as in Example 3, Step B to give the product as a very hygroscopic white solid. FAB MS 364.09 (MH+) Hi NMR (CD3OD, 500 MHz) δ 2.62 (3H,s), 4.12 (2H,s), 5.36 (2H,s), 7.33 (H,s), 7.35-7.55 (13 H,m) ppm. EXAMPLE 77 1 -(4-Cyanobenzyl)-5-[ 1 -(4-biphenyl)- 1 -hydroxy]ethyl-2- methylimidazole Step A: l -Trityl-4-[l -(4-biphenyl)- l-hydroxy]ethyl-2- methylimidazole A 1.0M solution of EtMgBr in THF (4 mL, 4 mmol) was added to a solution of l -trityl-4-iodo-2-methylimidazole (1.8 g, 4 mmol) in dry CH2O2 (8mL) at room temperature. After 1 hour a solution of 4-acetylbiphenyl (780 mg, 4mmol) in dry CH2CI2 (4mL) was added and stirring at room temperture was continued for 16 hours. The reaction mixture was quenched with sat. NH4CI and then the product was extracted into CHCI3, dried and the solvent was evaporated. The residue was chromatographed (silica gel 0.5-10% MeOH-CHCl3) and further purified by crystallization from CHCI3- hexane to afford title compound, mp 231 -232°C. FAB MS 521.25 (MH+) H i NMR (CDCI3, 400 MHz) δ 1.60 (3H,s), 1.76 (3H,s), 6.65 (H,s), 7.13-7.18 (6H,m), 7.30-7.36 (10H, m), 7.42 (2H, t, J=7.2 Hz), 7.51 (4H,s), 7.57 (2H,dd, J=8.4 and 1.2 Hz) ppm. Step B 1 -(4-Cyanobenzyl)-5-[ 1 -(4-biphenyl)- 1 -hydroxyjethyl- 2-methylimidazole The title compound was prepared using the protocol described in Example 5, Step C using the product from Step A above and the corresponding amount of 4-cyanobenzyl alcohol. The residue was chromatographed (silica gel, 1.2-5.0% MeOH-CHCl3) to yield the title compound. FAB MS 394.16 (MH+) H i NMR (CDCI3, 500 MHz) δ 1.95 (3H,s), 2.18 (3H,2), 4.98 (H,d, J=17.6 Hz) 5.22 (H,d, J=17.6 Hz), 6.72 (2H, d, J=8.4 Hz), 7.16 (H,s), 7.28-7.37 (5H,m), 7.39 (2H,d, J=8.4 Hz), 7.42-7.47 (4H,m) ppm. EXAMPLE 78 l -(4-Cyanobenzyl)-5-(4-biphenylmethyl)-2-methylimidazole trifluoroacetate salt Step A: l-Trityl-4-(4-biphenylmethyl)-2-methylimidazole The title compound was prepared using the protocol described in Example 1 , Step A except using the corresponding amounts of 4-chloromethylbiphenyl and 1 -trityl-4-iodo-2- methylimidazole. FAB MS 491.31 (MH+) H i NMR (CDCL3, 400 MHz) δ 1.63 (3H,s), 3.88 (2H,s), 6.47 (H,s), 7.12-7.16 (6H, m), 7.29-7.34 (12H,m), 7.41 (2H,t, .1=7.6 Hz), 7.49 (2H,d, J=7.6Hz) 7.56 (2H, dd, J=8.8 and 0.8 Hz) ppm. Step B: 1 -4-Cyanobenzyl)-5-(4-bipheny lmethyl)-2- methylimidazole trifluoroacetate salt The title compound was prepared using the protocol described in Example 5, Step C using the product from Step A above and the corresponding amount of 4-cyanobenzyl alcohol but purified as in Example 3, Step B. Anal. Calc'd for C25H21 N3O.7O H2OO.4O TFA: C, 62.32; H, 4.48; N, 7.84. Found: C, 62.36; H, 4.42; N, 7.87 FAB MS 364.09 (MH+) H i NMR (CD3OD, 500 MHz) δ 2.58 (3H,s), 4.05 (2H,s), 5.49 (2H,s), 7.06 (2H, d, J=8.8Hz), 7.18 (2H, d J=8.8Hz), 7.33 (H,m), 7.39 (H,s), 7.42 (2H,m), 7.43 (2H,m), 7.51 (2H,m), 7.60 (2H,d, J=8.8.Hz) ppm. EXAMPLE 79 1 -(4-Cvanobenzyl)-5-_ 1 -(4-biphenyl)lethyl-2-methyl imidazole The alcohol from Example 77 (181 mg, 460 mmol) dissolved in CH2CI2 (8mL) and this solution was added to a mixture of trimethylsilyl chloride (770 mL, όmmol) and Nal (900 mg, 6 mmol). The dark mixture was stirred at room temperature for 20 hours.The reaction mixΦre was distributed between H2O (100 mL) and CHCI3 (50 mL). The organic layer was washed with saturated Na2S2θ3 and water. The solvent was evaporated and the residue was chromatographed (silica gel, 2.5-5% CH3OH-CHCI3) to afford the title compound. Anal. Calc'd for C26H 2 3N3-0.15 CHCI3; C, 79.43; H, 5.90; N, 10.63. Found: C, 79.21 ; H, 5.74; N, 10.06. FAB MS 378.13 (MH+) Hi NMR (CDCI3, 400 MHz) δ 1.59 (3H, d, J=7.2 Hz), 2.27 (3H,s), 3.74 (H,q, J=7.2 Hz). 4.76 (H,d, J=18 Hz), 4.93 (H,d, J=18 HZ, 6.83 (2H,d, J=8.4Hz), 7.05-7.09 (3H, m), 7.32-7.36 (H,m) 7.38-7.46 (4H,m) 7.48-7.53 (4H,m) ppm. EXAMPLE 80 l -(4-Cyanobenzyl-5-f l-(4-biphenyPlvinylidene-2-methylimidazole The alcohol from Example 77 (59 mg, 150 μmol) was stirred in TFA (1 mL) at 55°C for 20 hours. The clear solution was then cooled and distributed between EtOAc and sat. NaHC0 3 . The organic layer was separated, dried and the solvent was evaporated. The residue was chromatographed (silica gel. 2.5% CH3OH-CHCI3) to afford the title compound. Anal. Calc'd for C26H21N3O.O5 CHCI3O.25 CH3OH; C, 81.10; H, 5.71 ; N. 10.79 Found: C, 81.43; H, 6.08; N, 10.59. FAB MS 376.43 (MH+) Hi NMR (CDCI3, 400 MHz) δ 2.34 (3H,s), 4.83 (2H,s), 5.32 (H,d, J=1.2 Hz), 5.56 (H,d, =1.2 Hz), 6.90 (2H, d, .1=8.4 Hz), 7.10 (H,s), 7.26-7.29 (2H,m) 7.34-7.39 (H,m), 7.43-7.59 (8H,m) ppm. EXAMPLE 81 l-(4-Cyanobenzyl)-5-[2-(4-biphenyl)Jvinylene-2-methylimidazole trifluoroacetate salt Step A: 1 -Trityl-4-[(2-(4-biphenyl)lvinylene-2-methyl imidazole The title compound was prepared using the protocol described in Example 30 using l -trityl-4-iodo-2-methylimidazole. The dark solution was cooled and chromatographed (silica gel, 0.5% MeOH-CHCl3) and rechromatographed (silica gel, 20% EtOAc-hexane) to give product as a 3: 1 mixture of the desired 1 ,2 vinylene and 1 , 1 vinylidene as evidenced by NMR. FAB MS 503.39 (MH+) Step B: 1 -(4-Cyanobenzyl)-5-[2-(4-biphenyl)]vinylene-2- methyimidazole trifluoroacetate salt The title compound was prepared using the protocol described in Example 5, Step C using the corresponding amounts of the product from Step A above and 4-cyanobenzyl alcohol. Anal. Calc'd for C26H2l N3 « 1.25 TFA-0.60 H2O: C, 64.73; H, 4.47; N, 7.95 Found: C, 64.71 ; H, 4.47; N. 7.82 FAB MS 376.08 (MH+) Hi NMR (CD3OD, 500 Hz) δ 2.67 (3H,s), 5.70 (2H,s), 6.98 (H,d, J=16.7 Hz), 7.29 (H,d, J=16.7 Hz), 7.34 (H,m), 7.39-7.46 (4H,m) 7.57 (2H,d, J=7.5 Hz), 7.61 -7.64 (4H,m) 7.79 (2H, d, J=9Hz), 7.86 (H,s) ppm. EXAMPLE 82 In vitro inhibition of ras famesyl 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 ah, J. Biol. Chem. 265:14701-14704 (1990), Pompliano, et aJL, Biochemistry 31 :3800 (1992) and Gibbs et ah, PNAS U.S.A. 86:6630-6634 (1989), respectively. Bovine FPTase was assayed in a volume of 100 μl containing 100 mM V-(2-hydroxy ethyl) piperazine-/V'-(2-ethane sulfonic acid) (HEPES), pH 7.4, 5 mM MgCl2, 5 mM dithiothreitol (DTT), 100 mM [3H]-famesyl diphosphate ( Hj-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 [3H1-FPP was utilized during the reaction period. Purified compounds were dissolved in 100% dimethyl sulfoxide (DMSO) and were diluted 20-fold into the assay. Percentage inhibition is measured by the amount of incoφoration of radioactivity in the presence of the test compound when compared to the amount of incoφoration in the absence of the test compound. Human FPTase was prepared as described by Omer et al-, Biochemistry 32:5167-5176 (1993). Human FPTase activity was assayed as described above with the exception that 0.1 % (w/v) polyethylene glycol 20,000, 10 μM ZnCl 2 and 100 ΠM Ras-CVIM were added to the reaction mixture. Reactions were performed for 30 min., stopped with 100 μl of 30% (v/v) trichloroacetic acid (TCA) in ethanol and processed as described above for the bovine enzyme. The compounds of the instant invention described in the above Example 1-31 were tested for inhibitory activity against human FPTase by the assay described above and were found to have IC50 of <50 μM. EXAMPLE 83 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 semm 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 famesylated and nonfarnesylated ras proteins are compared to determine the percent inhibition of famesyl transfer to protein. EXAMPLE 84 In vivo growth inhibition assay To determine the biological consequences of FPTase inhibition, the effect of the compounds of the instant invention on the anchorage-independent growth of Ratl cells transformed with either a v-ras, v-raf, or v-mos oncogene is tested. Cells transformed by v-Raf and v-Mos maybe included in the analysis to evaluate the specificity of instant compounds for Ras-induced cell transformation. Rat 1 cells transformed with either v-ras, v-raf, or v-mos are seeded at a density of 1 x 10 4 cells per plate (35 mm in diameter) in a 0.3% top agarose layer in medium A (Dulbecco's modified Eagle's 62 medium supplemented with 10% fetal bovine semm) over a bottom agarose layer (0.6%). Both layers contain 0.1 % methanol or an appro¬ priate 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 famesyl-protein transferase of the formula A: wherein: Rla and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, Rl lS(0) m -, R!0C(O)N 10-, Rl lC(0)0-, (RlO) 2 NC(0)-, R!0 N-C(NR10)-, CN, N02, RlOc(O)-, N3, -N(RlO)2, or Rl 10C(0)NR10_, c) unsubstituted or substituted Cl-Cό alkyl wherein the substituent on the substiΦted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, RlOO-, Rl lS(0)πr, R!0C(O)NR10-, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10- ; R 2 , R , R4 and R^ are independently selected from: a) hydrogen, 64 b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0) m -, RlOC(0)NRlO-, (Rl0) 2 NC(O)-, Rl lC(0)0-, Rlθ2N-C(NRl )-, CN, Nθ2, Rl°C(0)-, N3, -N(RlO) 2 , orRHOC(O)NRl0-, c) unsubstituted C l -Co alkyl, d) substituted Cl -Co alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0) m -, R10C(O)NR10-, (RlO) 2 NC(0)-, Rl°2N-C(NRl0)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10- ; Ob 5 R6C 5 Rod a nd R 6e are independently selected from: a) hydrogen, b) unsubstituted or substiΦted aryl, unsubstituted or substimted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, R 1 !S(0) m -, Rl C(0)NRlO-, (Rl0) 2 NC(O)-, R 1 lC(0)0-, Rl0 2 N-C(NRlO)-, CN, N02, R 10 C(O)-, N3, -N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstiΦted C 1 -Co alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstiΦted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, Rl lS(O) m NRl0-, (RlO) 2 NS(0) m -, Rl3c(O)NRl0-, (RlO) 2 NC(0)-, R10 2 N-C(NR10)-, CN, RIOC(O)-, N3, -N(RlO) 2 , and Rl 10C(0)-NR10_ ; any two of R 6a , R 6b , R6C 5 R6d a nd R 6e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3S provided that when R 2 , R3, R , R5, R6a, Rόb, R6C, Rod or Rόe is unsubstituted or substituted heterocycle, attachment of R 2 , R3, R4, R5, Rόa, R6b R6C, R6d or Roe t0 the phenyl ring is through a substitutable heterocycle ring carbon; R7 is selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Cl -4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, f) -S0 2 R 1 1 g) N(RlO) 2 or h) Cl-4 perfluoroalkyl; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, R lOO-, R l l S(0) m -, R l0C(O)NRl0-, (R lO) 2 NC(0)-, R l°2N-C(NRl O)-, CN, N02, Rl°C(0)-, N3, -N(R lO) 2 , or Rl lθC(O)NRl0-, and c) Cj -Cό alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, perfluoroalkyl, F, Cl, Br, RlOO-, RllS(0) m -, Rl0C(O)NH-, (RlO) NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , or Rl0θC(O)NH-; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9 is independently selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, halogen, Rl lO-, Rl lS(0) m -, R10C(O)NR10-, (Rl0)2NC(O)-, Rl0 2 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3, -N(RlO)2, or Rl 10C(0)NR10-, and c) Cl-Cό alkyl unsubstiΦted or substituted by Cl-Cό perfluoroalkyl, F, Cl, Br, RlOO-, Rl lS(0) m -, RlOC(0)NRlO-, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , or Rl 10C(0)NR10_ ; RlO is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl -Co alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substiΦted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl3 is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(R 10)2, benzyl and aryl; Al and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, -NR1°C(0)-, O, -N(R10)-, -S(O)2N(Rl0)-, -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 a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, provided that V is not hydrogen if Al is S(0) and V is not hydrogen if Al is a bond, n is 0 and A 2 is S(0)m", provided that when V is heterocycle, attachment of V to R8 and to A is through a substitutable ring carbon; W is a heterocycle; X is a bond, -CH=CH-, O, -C(=0)-, -C(0)NR7-, -NR7C(0)-, -C(0)0-, -OC(O)-, -C(0)NR7C(0)-, -S(0)2N(RlO)_, -N(Rl0)S(O)2- or -S(=0) m -; m is 0, 1 or 2; n is independently 0, 1 , 2, 3 or 4; p is independently 0, 1, 2, 3 or 4; q is 0, 1, 2 or 3; r is 0 to 5, provided that r is 0 when V is hydrogen; and t is 0 or 1; or a pharmaceutically acceptable salt thereof. 2. The compound according to Claim 1 of the formula A: wherein: Rla is independently selected from: hydrogen, C3-C10 cycloalkyl, RlOO-, -N(RlO)2, F or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -N(R1°)2, F or C2-C6 alkenyl, c) unsubstituted or substituted C l -Co alkyl wherein the substituent on the substituted C 1 -Co alkyl is selected from unsubstiΦted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO- and -N(R J 0)2; R 2 , R , R4 and R^ are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 0-, Rl lS(0) m -, RlOC(0)NRlO_, (RlO) 2 NC(0)-, R10 2 N-C(NR10)-, CN, N02, Rl°C(0)-, N3, -N(R!0)2, orRllOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl; d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 0-, RllS(O) m -,Rl0c(O)NRl0-,(Rl0) 2 NC(O)-, Rl0 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(R10) 2 , and R11OC(O)-NR10- ; RfSa, R όb 5 R6C 5 Rod an d R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 1 2 0-, R 11 S(0) m -, R 10C(O)NR 10-, (R 10) 2 NC(O)-, Rl0 2 N-C(NRlO)_, CN,Nθ2, Rl°C(0)-, N3, -N(RlO) 2 , orRllθC(O)NRl0-, c) unsubstituted C l -Co alkyl; d) substiΦted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 0-, Rl lS(0)m-, R 1 ^(O^NRlO-, (RlO) 2 NS(0) m -, R1 C(O)NR10-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and Rl 10C(0)-NR10- ; any two of R°Λ R6b R6 C ? Rod a nd R^e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R , R4, R5, ROa, ROb ? R6C ? Rod or R6e is unsubstituted or substituted heterocycle, attachment of R 2 , R3, R4, R5, R6a ( R 6b, ROC, R 6d or R 6e t0 the phenyl ring is through a substitutable heterocycle ring carbon; R is selected from: H; Cl-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C]-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, f) -S0 2 R 11 g) N(Rl ) 2 or h) Cl-4 perfluoroalkyl; R8 i independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C] -Co perfluoroalkyl, F, Cl, RlOO-, R1 C(O)NR10-, CN, N02, (RlO)2N-C(NRlO)-, RlOc(O)-, -N(RlO)2, or RllOC(O)NRl0_,and c) Cl-Cό alkyl substiΦted by C 1 -Co perfluoroalkyl , R 1 0 O- , Rl0c(O)NRl0-, (Rl0) 2 N-C(NRl0)-, RlOc(O)-, -N(R 10)2, or R 11 OC(0)NR 10-; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9 is independently selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, Rl lO-, Rl lS(0) m -, R!0C(O)NR10-, (Rl0) 2 NC(O)-, CN, NO2, (RlO)2N-C(NRlO)-, RlOc(O)-, -N(Rl ) 2 , 0 r RHOC(O)NR10-, and c) C l -Co alkyl unsubstituted or substituted by C l -Co perfluoroalkyl, F, Cl, RlOO-, RHS(0) m -, R!0C(O)NR10- (RlO) 2 NC(0)-, CN, (RlO)2N-C(NRlO)-, RIOC(O)-, -N(Rl )2, or Rl 1OC(O)NR10- ; RlO is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cj-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl3 is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(RlO)2, benzyl and aryl; Aland A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(O)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl 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. provided that when V is heterocycle, attachment of V to R8 and to A 1 is through a substitutable ring carbon; W is a heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, triazolyl or isoquinolinyl; X is a bond, O, -C(=0)-, -CH=CH-, -C(0)NR7-, -NR7C(0)-, -S(O)2N(Rl0)_, -N(Rl0)S(O)2- or -S(=0) m -; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; p is independently 0, 1, 2, 3 or 4; q is 0, 1, 2 or 3; r is 0 to 5, provided that r is 0 when V is hydrogen; and t is 0 or 1 ; or a pharmaceutically acceptable salt thereof. 3. The compound according to Claim 1 of the formula B: wherein: Rla is independently selected from: hydrogen, C3-C10 cycloalkyl, R OO-, -N(RlO) 2 , F or Cl -Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -N(RlO)2, F or C2-C6 alkenyl, c) unsubstituted or substituted Cl-Cό alkyl wherein the substituent on the substituted C l -Co alkyl is selected from unsubstituted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, RlOO- and -N(RlO) 2 ; R 2 and R3 are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 0-, RllS(O) m -,Rl0C(O)NRl0-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)_, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0_, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0) m -, Rl0c(O)NRl0-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, Rl C(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0- ; Roa, R6b ? R6C 5 Rod and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR10-, (R10 )2 NC(O)-, Rl0 2 N-C(NRlO)-, CN,Nθ2, Rl°C(0)-, N3,-N(Rl0) 2 , orRllOC(O)NRl0_, c) unsubstituted C 1 -Co alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl -Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 0-, Rl lS(0) m -, Rl l S(O) m NRl0-, (RlO) 2 NS(0) m -, Rl3C(O)NRl0-, (RlO) 2 NC(0)-, R 10 2 N-C(NR10>, CN, Rl°C(0)-, N3, -N(RlO)2, and Rl 10C(0)-NR 10_ ; any two of R°\ R6b, R6C ? Rod an(J Rόe 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3 provided that when R 2 , R , R6a, ROb, R6C ? Rod or R6e i s unsubstiΦted or substi ted heterocycle, attachment of R 2 , R3, R6a ? Rόb, R6C, Rod or R6e t0 the phenyl ring is through a substiΦtable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, Cl -Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl -Cό perfluoroalkyl, F, Cl, Rl O-, R10C(O)NR 10-, CN, N02, (R 10) 2 N-C(NR 10)-, RlOc(O)-, -N(RlO)2, or R HOC(O)NR10_, and c) Cl-Cό alkyl substituted by C1 -C6 perfluoroalkyl, Rl°0-, R!0C(O)NR 10-, (R 10) 2 N-C(NR 1°)-, RlOC(O)-, -N(R 1 °)2, or R 1 1 OC(0)NR 1 - ; provided that when R is heterocycle, attachment of R to V is through a substitutable ring carbon; R9a and R9 are independently hydrogen, C l -Cό alkyl, trifluoromethyl and halogen; RlO is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-C6 heteroaralkyl, Cl-C6 substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(R O)2, benzyl and aryl; A and A 2 are independently selected from: a bond, -CH=CH-, -CHC-, -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, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl and thienyl, c) aryl, d) C1-C20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C20 alkenyl, and provided that V is not hydrogen if Al is S(0)m and V is not hydrogen if Al is a bond, n is 0 and A 2 is S(0)m. provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)-; m is 0, 1 or 2; n is independently 0, 1 , 2, 3 or 4; p is 0, 1 , 2, 3 or 4; and r is 0 to 5, provided that r is 0 when V is hydrogen; or a pharmaceutically acceptable salt thereof. 4. The compound according to Claim 1 of the formula C: wherein: Rl a is independently selected from: hydrogen, C3-C10 cycloalkyl, R lOO-, -N(R lO)2, F or Cl-Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -N(R 10 )2, F or C2-C6 alkenyl, c) unsubstituted or substituted Cl -Cό alkyl wherein the substiΦent on the substituted Cl -Cό alkyl is selected from unsubstituted or substituted aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, R OO- and -N(RlO) 2 ; R 2 and R3 are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, Rl°C(O)NRl0-, CN(Rl0) 2 NC(O)-, R!0 2 N-C(NR10)-, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , orRHOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R 1 2 0-, R 11 S(0) m -, R l °C(0)NR 10_, (R 10) 2 NC(O)-, R!0 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10- ; R6a 5 R6b ? R6C 5 Rod and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R 10 C(O)NRl0-, CN(Rl0) 2 NC(O)-, R!0 2 N-C(NR10)-, CN,N02, Rl°C(0)-, N3,-N(R 10 )2, orRllOC(O)NR!0-, c) unsubstituted C 1 -Co alkyl, d) substiΦted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, R* lS(O) m NRl0-, (Rl0 )2 NS(O) m -, Rl3C(O)NRl0-, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(Rl ) , and Rl lOC(O)-NRl0-; any two of R°Λ R6b, R6C, Rod nd R oe on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R , R6a, R6b. ROC, Rod or R6e i s unsubstituted or substituted heterocycle, attachment of R 2 , R3, R6a ? Rόb, ROC, Rod or R6e to the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, RlOO-, R!0C(O)NR10-, CN, NO2, (Rl0)2N-C(NRl0)-, R10C(O)-, -N(RlO)2, or RllOC(O)NRl0-, and c) Cl-Cό alkyl substituted by Cl-Cό perfluoroalkyl, Rl°0-, Rl0C(O)NRl0-, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(R 10) , or R 11 OC(0)NR 10-; provided that when R8 i heterocycle, attachment of R8 to V is through a substitutable ring carbon; R and R b are independently hydrogen, Cl-Cό alkyl, trifluoromethyl and halogen; RlO is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substiΦted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Rl is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, -CH2N(R O)2, benzyl and aryl; Al and A 2 are independently selected from: a bond, -CH=CH-, -C≡C-, -C(0)-, -C(O)NRl0-, O, -N(RlO)-, or S(0) m ; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, imidazolinyl, pyridinyl, thiazolyl, oxazolyl, indolyl, quinolinyl, isoquinolinyl, triazolyl and thienyl, 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, 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. provided that when V is heterocycle, attachment of V to R8 and to Al is through a substitutable ring carbon; X is a bond, -CH=CH-, -C(O)NRl0-, -NRIO O)-, O or -C(=0)-; m is 0, 1 or 2; n is independently 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4, provided that p is not 0 if X is a bond, -NRlOC(O)-, -NRlO- or O; and r is 0 to 5, provided that r is 0 when V is hydrogen; or a pharmaceutically acceptable salt thereof. 5. The compound according to Claim 3 of the formula D: wherein: Rla is independently selected from: hydrogen, C3-C10 cycloalkyl or Cl-Cό alkyl; Rib i independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C 10 cycloalkyl, RlOO-, -N(R 10)2, F or C2-C6 alkenyl, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, Rl O-, or -N(RlO) 2; R 2 is selected from: a) hydrogen, b) unsubstituted or substiΦted aryl, unsubstituted or substituted heterocycle, C3- 0 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 0-, Rl lS(0) m -, R!0C(O)NR10-, (RlO) 2 NC(0)-, R10 2 N-C(NR10)-, CN, N0 , RlOc(O)-, N3, -N(Rl ) 2 , orRllOC(O)NRl0-, c) unsubstituted Cj-Cό alkyl, d) substituted Cl -Co alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R12O, RllS(0) m -, R! C(O)NR10-, (R!0) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) 2 , and R11OC(O)-NR10- ; R is selected from H, halogen, Cl-Cό alkyl and CF3; Rόa, R6b, R6C 5 Rod and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 12o-, RllS(0)m-, R 10 C(O)NRl0-, (Rl0) 2 NC(O)-, Rl0 2 N-C(NRl )-, CN,N02, Rl°C(0)-, N3, -N(RlO) 2 , orRUOC(O)NRl0-, c) unsubstiΦted C 1 -Co alkyl, d) substiΦted Cl-Cό alkyl wherein the substiΦent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substiΦted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR10-, (Rl0) 2 NC(O)-, R10 2 N-C(NR1°)-, CN, Rl°C(0)-, N3, -N(Rl ) 2 , and R110C(0)-NR10-; any two of R6a, R6b ? R6C, Rod an d R° e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3 provided that when R 2 , R6a, R6b, ROC, Rod or R6e \ unsubstituted or substituted heterocycle, attachment of R 2 , R6a, R6b, ROC, Rod or Rόe t0 the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, C l-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, RlOO-, R10C(O) R10_, CN, Nθ2, (RlO) 2 N-C(NRlO)-, RlOc(O)-, -N(RlO)2, or Rl lθC(O)NRl0-, and c) Cl-Cό alkyl substituted by Cl-Cό perfluoroalkyl, R OO-, R10C(O)NR10_, (RlO) 2 N-C(NRlO)_, RlOc(O)-, -N(RlO)2, or Rl 10C(0)NR10- ; or provided that when R is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R a and R b are independently hydrogen, halogen, CF3 or methyl; RlO is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; R 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl -Cό substituted aralkyl, C] -C6 heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; Al is selected from: a bond, -C(O)-, O, -N(RlO)_. Q r S(0) m ; X is a bond, -CH=CH-, -C(O)NRl0-, -NR OC(O)-, O or -C(=0)-; n is 0 or 1 ; provided that n is not 0 if Al is a bond, O, -N(Rl0)-, or S(O) m ; m is 0, 1 or 2; and p is 0, 1 , 2, 3 or 4; or the pharmaceutically acceptable salts thereof. 6. The compound according to Claim 4 of the formula E: A 1 (CR R 8 wherein: R la is independently selected from: hydrogen, R lOO-, -N(R 10) 2 , F, C3-C10 cycloalkyl or Cl -Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -NCR 1 0)2, F or C2-C6 alkenyl, c) Cl-Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, Rl°0-, or -N(RlO) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3- 0 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cj -Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R 10 C(O)NRl0 . , (Rl0) 2 NC(O)-, 84 Rl0 2 N-C(NRlO)_, CN,N02, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R12O-, RllS(O) m -,Rl0c(O)NRl0_, (Rl0) 2 NC(O)-, Rl0 2 N-C(NRl )-, CN, RlOC(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0-; R is selected from H, halogen, Cl-Cό alkyl and CF3; Rόa, R6b, R6C, Rod a nd R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstiΦted or substiΦted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, RllS(0) m -, R!0C(O)NR10-, (Rl0) 2 NC(O)-, Rl0 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(0)NRlO-, c) unsubstituted C l -Co alkyl, d) substituted Cl-Cό alkyl wherein the substiΦent on the substiΦted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substiΦted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, R12O-, RllS(0) m -,RlOC(0)NRlO_, (Rl0) 2 NC(O)-, R10 2 N-C(NR10)-, CN, Rl C(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0-;or any two of R°\ R6b, R6C, Rod a nd R^e on adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R°A R6b, R6C, Rod or Rόe [ s unsubstituted or substituted heterocycle, attachment of R 2 , R6a . R 6b , R6C, Rod or Rόe to the phenyl ring is through a substitutable heterocycle ring carbon; R8 is independently selected from: a) hydrogen, b) aryl, substituted aryl, heterocycle, substituted heterocycle, Cl-Cό alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cl-Cό perfluoroalkyl, F, Cl, RlOO-, R10C(O)NR 10-, CN, N02, (RlO)2N-C(NRlO)-, RlOc(O)-, -N(RlO)2, or Rl lOC(O)NRl0-, and c) Cl-Cό alkyl substituted by Cl-Cό perfluoroalkyl, Rl°0-, R!0C(O)NR10-, (R10) 2 N-C(NR10)-, RlOc(O)-, -N(RlO)2, or Rl lθC(O)NRl0- ; provided that when R8 is heterocycle, attachment of R8 to V is through a substitutable ring carbon; R9a and R are independently hydrogen, halogen, CF3 or methyl; R O is independently selected from hydrogen, Cl-Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; RU is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl -Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)-; n is 0 or 1 ; m is 0, 1 or 2; and p is 0, 1 , 2, 3 or 4, provided that p is not 0 if X is a bond or O; or the pharmaceutically acceptable salts thereof. 7. The compound according to Claim 5 of the formula F: wherein: R la is independently selected from: hydrogen, C3-C10 cycloalkyl or Cl -Cό alkyl; Ri is independently selected from: a) hydrogen, b) aryl, heterocycle, C3-C10 cycloalkyl, RlOO-, -N(R l°)2 or F, c) Cl -Cό alkyl unsubstituted or substituted by aryl, heterocycle, C3-C10 cycloalkyl, Rl O-, or -N(R l O) 2 ; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, Rl 2 0-, Rl lS(0)m-, R!0C(O)NR10-, (R!0) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3,-N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substiΦted Cl-Cό alkyl wherein the substiΦent on the substiΦted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, RllS(0) m -, R!0C(O)NR10_, (RlO) 2 NC(0)-, R!0 2 N-C(NR10)-, CN, RlOC(O)-, N3, -N(Rl ) , and R11OC(O)-NR10- ; R is selected from H, halogen, CH3 and CF3; Rόa, Rόb, ROC, Rod and R 6e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substiΦted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 12o-, Rl lS(0) m -, R 10 C(O)NRl0-, (RlO) 2 NC(0)-, Rl0 N-C(NRlO)-, CN, N02, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0_, c) unsubstituted Cl-Cό alkyl, d) substituted C 1 -Co alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl2 0 -, Rl lS(0)m-, R!0C(O)NR10_, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOc(O)-, N3, -N(Rl ) 2 , and RllOC(O)-NRl0- ; or provided that when R2, R6a ? 6b, ROC, Rod or R6e j s unsubstituted or substituted heterocycle, attachment of R 2 , R6a, R6b, R6C, Rod or R e to the phenyl ring is through a substitutable heterocycle ring carbon; R9 and R are independently hydrogen, halogen, CF3 or methyl; RlO is independently selected from hydrogen, Cl-Cό alkyl, benzyl and aryl; Rl 1 is independently selected from Cl-Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl-Cό alkyl, Cl-Cό aralkyl, Cl-Cό substituted aralkyl, Cl-Cό heteroaralkyl, Cl-Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl-Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; X is a bond, -CH=CH-, -C(O)NRl0-, -NR10C(O)-, O or -C(=0)- m is 0, 1 or 2; and p is 0, 1, 2, 3 or 4; or the pharmaceutically acceptable salts thereof. 8. The compound according to Claim 6 of the formula G: G wherein: Rla is independently selected from: hydrogen, R l°0-, -N(R l°) 2 , F, C3-C10 cycloalkyl or Cl -Cό alkyl; Rib is independently selected from: a) hydrogen, b) aryl, heterocycle or C3-C10 cycloalkyl, c) Cl-Cό alkyl unsubstituted or substiΦted by aryl, heterocycle, C3- 0 cycloalkyl, C2-C6 alkenyl, R l°0-, or -N(RlO) 2; R 2 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstiΦted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl -Cό perfluoroalkyl, R ] 2 0-, R l l S(0)m-, R Mc^NR iO-, (R l°)2NC(0)-, R !0 2 N-C(NR 10)-, CN, N02, R 10 C(O)-, N3, -N(R lO) 2 , or Rl lOC(O)NR l0-, c) unsubstiΦted C 1 -Co alkyl, d) substiΦted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substiΦted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, 90- R12O-, Rl lS(0) m -, R 10 C(O)NRl0-, (RlO) 2 NC(0)-, R10 2 N-C(NR10)_, CN, RlOC(O)-, N3, -N(RlO) 2 , and RllOC(O)-NRl0- ; R3 is selected from H, halogen, CH3 and CF3; R6a, Rόb, R6C, Rod an d R e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, Cl-Cό perfluoroalkyl, R 1 2 0-, R 11 S(0)m-, R 10C(O)NR 10-, (R 10) 2 NC(O)-, Rl0 2 N-C(NRlO)-, CN, Nθ2, Rl°C(0)-, N3, -N(RlO) 2 , orRllOC(O)NRl0-, c) unsubstituted Cl-Cό alkyl, d) substituted Cl-Cό alkyl wherein the substituent on the substituted Cl-Cό alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Rl 2 0-, Rl lS(0)m-, R 10 C(O)NRl _, (RlO) 2 NC(0)-, Rl0 2 N-C(NRlO)-, CN, RlOC(O)-, N3, -N(RlO) , and RllOC(O)-NRl0-;or any two of R6a, Rόb, R6C, Rod nd R^e 0 n adjacent carbon atoms are combined to form a diradical selected from -CH=CH-CH=CH-, -CH=CH-CH2-, -(CH2)4- and -(CH2)3-; provided that when R 2 , R6a, R6b, R6C, R6d or Roe i s unsubstituted or substituted heterocycle, attachment of R 2 , R 6a , R 6b , R6c, R6d or R6e to the phenyl ring is through a substitutable heterocycle ring carbon; R9a and R9 are independently hydrogen, halogen, CF3 or methyl; R lO is independently selected from hydrogen, Cl -Cό alkyl, 2,2,2- trifluoroethyl, benzyl and aryl; Rl 1 is independently selected from Cl -Cό alkyl and aryl; Rl 2 is independently selected from hydrogen, Cl -Cό alkyl, Cl -Cό aralkyl, Cl -Cό substiΦted aralkyl, Cl -Cό heteroaralkyl, Cl -Cό substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, substituted heteraryl, Cl -Cό perfluoroalkyl, 2-aminoethyl and 2,2,2-trifluoroethyl; A l is selected from: a bond, -C(O)-, O, -N(R 10)-, or S(0) m ; m is 0, 1 or 2; and n is 0 or 1 ; or the pharmaceutically acceptable salts thereof. 9. A compound which inhibits famesyl-protein transferase which is: l -(4-Cyanobenzyl)-5-(4'-phenylbenzamido)ethyl-imidazole l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole l-(4-Biphenylethyl)-5-(4-cyanobenzyl)imidazole l -(2'-Bromo-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole 1 -(2'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(3',5'-dichloro)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-Methoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(3-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(3',5'-Bis-trifluoromethyl)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)-4- methylimidazole l-(4-Biphenylmethyl)-5-(4-cyanophenyloxy)-imidazole 5-(4-Cyanophenyloxy)- 1 -(2'-methyl-4-biphenylmethyl)-imidazole 5-(4-Biphenyloxy)- 1 -(4-cyanobenzyl)-imidazole 5-(2'-Methyl-4-biphenoxy)- 1 -(4-cyanobenzyl)-imidazole 5-(4-(3',5'-dichloro)biphenylmethyl)-l -(4-cyanobenzyl)imidazole 1 -(4-biphenylmethyl)-5-( 1 -(R.S)-acetoxy- 1 -(4- cyanophenyl)methylimidazole 1 -(4-Biphenylmethy l)-5-( 1 -(R,S)-hydroxy- 1 -(4-cyanophenyl) methylimidazole 1 -(4-Biphenylmethyl)-5-( 1 -(R,S)-amino- 1 -(4-cyanophenyl) methylimidazole 1 -(4-biphenylmethyl)-5-( 1 -(R,S)-methoxy- 1 -(4-cyanophenyl)- methylimidazole l -(4-Cyanobenzyl)-5-(l -hydroxy-l-(3-fluoro-4-biphenyl)-methyl)- imidazole l -(4-Cyanobenzyl)-5-(l -hydroxy- l -(3-biphenyl)methyl-imidazole 5-(2-[ 1 ,1 '-Biphenyl]vinylene)- 1 -(4-cyanobenzyl)imidazole 1 -(4-Biphenylmethyl)-5-(4-bromophenyloxy)-imidazole 1 -(3'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(4'-Methyl-4-biphenylmethy l)-5-(4-cyanobenzy 1) imidazole l -(3'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4'-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(3'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'3'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l-(2'4'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'5'-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(3 '-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-Fluoro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(4-(2'-Trifluoromethylphenyl)-2-Chlorophenylmethyl)-5-(4- cyanobenzyl) imidazole 1 - { 1 -(4-(2'-trifluoromethylphenyl)phenyl)ethyl } -5-(4-cyanobenzyl) imidazole l -(2'-Trifluoromethyl-4-biphenylpropyl)-5-(4-cyanobenzyl) imidazole 1 -(2'-N-t-Butoxycarbonylamino-4-biphenylmethyl)-5-(4- cyanobenzyl) imidazole l-(2'-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l-(2'-Acetylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Methylsulfonylaminomethyl-4-biphenylmethyl)-5-(4- cyanobenzyl) imidazole l -(2'-Ethylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Phenylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l-(2 ' -Glycinylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole l -(2'-Methyl-4-biphenylmethyl)-2-chloro-5-(4-cyanobenzyl) imidazole 1 -(2'-Methyl-4-biphenylmethyl)- 4-chloro 5-(4-cyanobenzyl) imidazole l -(3'-Chloro-2-methyl-4-biphenylmethyl)-4-(4- cyanobenzyl)imidazole l -(3'-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyPimidazole l-(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-4-(4- cyanobenzyl) imidazole l -(3'-Trifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3'-Methoxy-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(2'-Chloro-4'-fluoro-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(2'-Ethyl-4-biphenylmethyI)-5-(4-cyanobenzyl)imidazole l -(2'-(2-Propyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole l -(2'-(2-Methyl-2-propyl)-4-biphenylmethyl)-5-(4- cyanobenzy 1 )imidazole l -(2'-Ethyl-4-biphenylmethyl)-5-(4-( l/7-tetrazol-5- yl))benzyI)imidazole 1 -[ 1 -(4-Cyanobenzyl)imidazol-5-ylmethoxy]-4-(2'-methylphenyl)-2- (3-N-phthalimido- 1 -propy l)benzene 1 -(3',5 '-DitrifluoromethyI-2-methyl-4-biphenylmethy l)-5-(4- cyanobenzyl)imidazole l -(3',5'-Chloro-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l -(3',5'-Dimethyl-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzyl)imidazole l-(3-(N-Boc-aminomethyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)- imidazole l -(3-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole l -(4-Cyanobenzyl)-2-methyl-5-(2'-methylbiphenyl-4- yloxy)imidazole 5-(4-Cyanobenzyl)-l-(3-cyano-2'-trifluoromethylbiphenyl-4-ylmethyl)- imidazole 2-Amino-5-(biphenyl-4-ylmethyl)- 1 -(4-cyanobenzyl)imidazole 2- Amino- 1 -(biphenyl-4-ylmethyl)-5-(4-cyanobenzyl)imidazole l -(3-Butylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole l-(3-Propylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole l -(4-Biphenylmethyl)-4-(4-cyanobenzyl-2-methylimidazole l-(4-Cyanobenzyl)-5-L(3-fluoro-4-biphenyl)methyl]imidazole 1 -(4-Cyanobenzyl)-5-[ 1 -(4-biphenyl)- 1 -hydroxy ]ethyl-2- methylimidazole l -(4-Cyanobenzyl)-5-(4-biphenylmethyl)-2-methylimidazole l-(4-Cyanobenzyl)-5-[ l -(4-biphenyl)]ethyl-2-methyl imidazole 1 -(4-Cyanobenzyl-5-[ 1 -(4-biphenyl)]vinylidene-2-methylimidazole or 99 l -(4-Cyanobenzyl)-5-[2-(4-biphenyl)]vinylene-2-methylimidazole or a pharmaceutically acceptable salt or optical isomer thereof. 10. The compound according to Claim 9 which is: l -(2'-Methoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 1 1. The compound according to Claim 9 which is: 1 -(2'-Methyl-4-biphenylmethyl)-5-(4-cyanobenzy 1) imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 12. The compound according to Claim 9 which is: 1 -(4-(3',5'-dichloro)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 13. The compound according to Claim 9 which is: 1 -(4'-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 14. The compound according to Claim 9 which is: 5-(2'-Methyl-4-biphenoxy)- 1 -(4-cyanobenzyl)-imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 15. The compound according to Claim 9 which is: l -(4-Cyanobenzyl)-5-(l -hydroxy- l-(3-fluoro-4-biphenyl)-methyl)- imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 16. The compound according to Claim 9 which is: 1 -(2',5 '-Dichloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole or a pharmaceutically acceptable salt or optical isomer thereof. 17. The compound according to Claim 9 which is: l-(3'-Methoxy-2-methyl-4-biphenylmethyl)-5-(4- cyanobenzy1)imidazole 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 3. 20. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 4. 21. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of Claim 9. 22. A method for inhibiting famesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 23. A method for inhibiting famesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 19. 24. A method for inhibiting famesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 20. 25. A method for inhibiting famesyl-protein transferase which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21. 26. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 27. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 19. 28. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 20. 29. A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 21. 30. 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 18. 31. 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 18. 32. A method for treating infections from hepatitis delta and related vimses which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 33. A method for preventing restenosis which comprises administering to a mammal in need thereof a therapeutically effective amount of a composition of Claim 18. 34. 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 1 . 35. A pharmaceutical composition made by combining the compound of Claim 1 and a pharmaceutically acceptable carrier. 36. A process for making a pharmaceutical composition comprising combining a compound of Claim 1 and a pharmaceutically acceptable carrier.

Inventors: ANTHONY NEVILLE J, GOMEZ ROBERT P, HALCZENKO WASYL, HUTCHINSON JOHN H, SOLINSKY KELLY M, STOKKER GERALD E, WAI JOHN S, WILLIAMS THERESA M, YOUNG STEVEN D, ANTHONY, NEVILLE, J., GOMEZ, ROBERT, P., HALCZENKO, WASYL, HUTCHINSON, JOHN, H., SOLINSKY, KELLY, M., STOKKER, GERALD, E., WAI, JOHN, S., WILLIAMS, THERESA, M., YOUNG, STEVEN, D.
Applicants: ANTHONY NEVILLE J, GOMEZ ROBERT P, HALCZENKO WASYL, HUTCHINSON JOHN H, MERCK & CO INC, SOLINSKY KELLY M, STOKKER GERALD E, WAI JOHN S, WILLIAMS THERESA M, YOUNG STEVEN D, ANTHONY, NEVILLE, J., GOMEZ, ROBERT, P., HALCZENKO, WASYL, HUTCHINSON, JOHN, H., MERCK & CO., INC., SOLINSKY, KELLY, M., STOKKER, GERALD, E., WAI, JOHN, S., WILLIAMS, THERESA, M., YOUNG, STEVEN, D.
Application year: 1997
Main classification: C07D233
IPC codes: A61K31, A61P43, C07D213, C07D233, C07D401, C07D403, C07D409, C07D413, C07D417