Method of treating cancer

Abstract

The present invention relates to methods of treating cancer using a combination of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

1 . A method for achieving a therapeutic effect in a mammal in need thereof which comprises administering to said mammal amounts of at least two therapeutic agents selected from a group consisting of: 
 a) a prenyl-protein transferase inhibitor and    b) an antineoplastic agent.    
     
     
         2 . The method according to  claim 1  wherein an amount of a prenyl-protein transferase inhibitor and an amount of an antineoplastic agent are administered simultaneously.  
     
     
         3 . The method according to  claim 1  wherein an amount of an antineoplastic agent and an amount of a prenyl-protein transferase inhibitor are administered consecutively.  
     
     
         4 . The method according to  claim 1  wherein the therapeutic effect is treatment of cancer.  
     
     
         5 . The method according to  claim 4  wherein the therapeutic effect is selected from inhibition of cancerous tumor growth and regression of cancerous tumors.  
     
     
         6 . The method according to  claim 4  wherein the antineoplastic agent is selected from: 
 a) a microtubule-stabilising agent;    b) a microtubule-disruptor agent;    c) an alkylating agent;    d) an anti-metabolite;    e) epidophyllotoxin;    f) an antineoplastic enzyme;    g) a topoisomerase inhibitor;    h) procarbazine;    i) mitoxantrone;    j) a platinum coordination complexe;    k) a biological response modifier;    l) a growth inhibitor;    m) a hormonal/antihormonal therapeutic agent and    n) a haematopoietic growth factor.    
     
     
         7 . The method according to  claim 4  wherein the antineoplastic agent is a member of a class of anti-neoplastic agents, said class selected from: the anthracycline family of drugs, the vinca drugs, the mitomycins, the bleomycins, the cytotoxic nucleosides, the taxanes, the epothilones, discodermolide, the pteridine family of drugs, diynenes, aromatase inhibitors and the podophyllotoxins.  
     
     
         8 . The method according to  claim 4  wherein the antineoplastic agent is selected from: paclitaxel, docetaxel, epothilone A, epothilone B, desoxyepothilone A, desoxyepothilone B, doxorubicin, carminomycin, daunorubicin, aminopterin, methotrexate, methopterin, dichloro-methotrexate, mitomycin C, porfiromycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin, etoposide, etoposide phosphate, teniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine, estramustine, cisplatin, carboplatin, cyclophosphamide, bleomycin, tamoxifen, ifosamide, melphalan, hexamethyl melamine, thiotepa, cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide, leuprolide, a pyridobenzoindole derivative, an interferon and an interleukin.  
     
     
         9 . The method according to  claim 4  wherein the antineoplastic agent is selected from: paclitaxel, epothilone A, epothilone B, desoxyepothilone A, desoxyepothilone B, doxorubicin, daunorubicin, 5-fluorouracil, etoposide, vinblastine, estramustine, cisplatin, ara-C and bicalutamide.  
     
     
         10 . The method according to  claim 4  wherein the prenyl-protein transferase inhibitor is selected from: 
 2(S)-Butyl-1-(2,3-diaminoprop-1-yl)-1-(1-naphthoyl)piperazine;    1-(3-Amino-2-(2-naphthylmethylamino)prop-1-yl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-{5-[1-(2-naphthylmethyl)]-4,5-dihydroimidazol}methyl-4-(1-naphthoyl)piperazine;    1-[5-(1-Benzylimidazol)methyl]-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-{5-[1-(4-nitrobenzyl)]imidazolylmethyl}-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-(3-Acetamidomethylthio-2(R)-aminoprop-1-yl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-[2-(1-imidazolyl)ethyl]sulfonyl-4-(1-naphthoyl)piperazine;    2(R)-Butyl-1-imidazolyl-4-methyl-4-(1-naphthoyl)piperazine;    2(S)-Butyl-4-(1-naphthoyl)-1-(3-pyridylmethyl)piperazine;    1-2(S)-butyl-(2(R)-(4-nitrobenzyl)amino-3-hydroxypropyl)-4-(1-naphthoyl)piperazine;    1-(2(R)-Amino-3-hydroxyheptadecyl)-2(S)-butyl-4-(1-naphthoyl)-piperazine;    2(S)-Benzyl-1-imidazolyl-4-methyl-4-(1-naphthoyl)piperazine;    1-(2(R)-Amino-3-(3-benzylthio)propyl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-(2(R)-Amino-3-[3-(4-nitrobenzylthio)propyl])-2(S)-butyl-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-[(4-imidazolyl)ethyl]-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-[(4-imidazolyl)methyl]-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-[(1-naphth-2-ylmethyl)-1H-imidazol-5-yl)acetyl]-4-(1-naphthoyl)piperazine;    2(S)-Butyl-1-[(1-naphth-2-ylmethyl)-1H-imidazol-5-yl)ethyl]-4-(1-naphthoyl)piperazine;    1-(2(R)-Amino-3-hydroxypropyl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-(2(R)-Amino-4-hydroxybutyl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-(2-Amino-3-(2-benzyloxyphenyl)propyl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-(2-Amino-3-(2-hydroxyphenyl)propyl)-2(S)-butyl-4-(1-naphthoyl)piperazine;    1-[3-(4-imidazolyl)propyl]-2(S)-butyl-4-(1-naphthoyl)-piperazine;    2(S)-n-Butyl-4-(2,3-dimethylphenyl)-1-(4-imidazolylmethyl)-piperazin-5-one;    2(S)-n-Butyl-1-[1-(4-cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3-dimethylphenyl)piperazin-5-one;    1-[1-(4-Cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3-dimethylphenyl)-2(S)-(2-methoxyethyl)piperazin-5-one;    2(S)-n-Butyl-4-(1-naphthoyl)-1-[1-(1-naphthylmethyl)imidazol-5-ylmethyl]-piperazine;    2(S)-n-Butyl-4-(1-naphthoyl)-1-[1-(2-naphthylmethyl)imidazol-5-ylmethyl]-piperazine;    2(S)-n-Butyl-1-[1-(4-cyanobenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)piperazine;    2(S)-n-Butyl-1-[1-(4-methoxybenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)piperazine;    2(S)-n-Butyl-1-[1-(3-methyl-2-butenyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)piperazine;    2(S)-n-Butyl-1-[1-(4-fluorobenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)piperazine;    2(S)-n-Butyl-1-[1-(4-chlorobenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)piperazine;    1-[1-(4-Bromobenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-(1-naphthoyl)piperazine;    2(S)-n-Butyl-4-(1-naphthoyl)-1-[1-(4-trifluoromethylbenzyl)imidazol-5-ylmethyl]-piperazine;    2(S)-n-Butyl-1-[1-(4-methylbenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)-piperazine;    2(S)-n-Butyl-1-[1-(3-methylbenzyl)imidazol-5-ylmethyl]-4-(1-naphthoyl)-piperazine;    1-[1-(4-Phenylbenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-(1-naphthoyl)-piperazine;    2(S)-n-Butyl-4-(1-naphthoyl)-1-[1-(2-phenylethyl)imidazol-5-ylmethyl]-piperazine;    2(S)-n-Butyl-4-(1-naphthoyl)-1-[1-(4-trifluoromethoxy)imidazol-5-ylmethyl]piperazine;    1-{[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetyl}-2(S)-n-butyl-4-(1-naphthoyl)piperazine;    (S)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(methanesulfonyl)ethyl]-2-piperazinone;    (S)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)ethyl]-2-piperazinone;    (R)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone;    (S)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[N-ethyl-2-acetamido]-2-piperazinone;    (±)-5-(2-Butynyl)-1-(3-chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    1-(3-Chlorophenyl)-4-[-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    5(S)-Butyl-4-[1-(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]-1-(2,3-dimethylphenyl)-piperazin-2-one;    4-[1-(2-(4-Cyanophenyl)-2-propyl)-5-imidazolylmethyl]-1-(3-chlorophenyl)-5(S)-(2-methylsulfonylethyl)piperazin-2-one;    (S)-n-Butyl-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-1-(2-methylphenyl)piperazin-2-one;    4-[1-(4-Cyanobenzyl)-5-imidazolylmethyl]-5(S)-(2-fluoroethyl)-1-(3-chlorophenyl)piperazin-2-one;    4-[3-(4-Cyanobenzyl)pyridin-4-yl]-1-(3-chlorophenyl)-5(S)-(2-methylsulfonylethyl)-piperazin-2-one;    4-[5-(4-Cyanobenzyl)-1-imidazolylethyl]-1-(3-chlorophenyl)piperazin-2-one;    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylpropionyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-2-methyl-3-phenylpropionyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-2-methyl-3-phenylpropionyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-4-pentenoyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-4-pentenoyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxypentanoyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxypentanoyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]5-pentyloxy-4-methylpentanoyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-4-methylpentanoyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-methylbutanoyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3 (S)-methyl]pentyloxy-3-methylbutanoyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylbutanoyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-phenylbutanoyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3 (S)-methyl]pentylthio-2-methyl-3-phenylpropionyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentylthio-2-methyl-3-phenylpropionyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3 (S)-methyl]pentylsulfonyl-2-methyl-3-phenylpropionyl-homoserine lactone,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentylsulfonyl-2-methyl-3-phenylpropionyl-homoserine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine methyl ester,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine sulfone methyl ester,    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylpropionyl-methionine sulfone (Compound 6),    2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester,    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-naphth-2-yl-propionyt-methionine sulfone methyl ester,    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]-pentyloxy-3-naphth-2-yl-propionyl-methionine sulfone,    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-naphth-1-yl-propionyl-methionine sulfone methyl ester,    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-naphth-1-yl-propionyl-methionine sulfone,    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-methylbutanoyl-methionine methyl ester.    2-(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-methylbutanoyl-methionine,    Disulphide of 2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)methyl]pentyloxy-3-phenylpropionyl-homoserine lactone,    Disulphide of 2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)-methyl]pentyloxy-3-phenylpropionyl-homoserine,    Disulphide of 2(S)-[2(S)-[2(R)-Amino-3-mercapto]propylamino-3(S)methyl]pentyloxy-3-methylbutanoyl-methionine methyl ester    1-(4-Biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(4-Cyanobenzyl)-5-(4′-phenylbenzamido)ethyl-imidazole    1-(2′-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(4-Biphenylethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-Bromo-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Trifluoromethoxy-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(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    1-(3-Chloro-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(4-(3′,5′-Bis-trifluoromethyl)-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Trifluoromethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)-4-methylimidazole    1-(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)-1-(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-Biphenylmethyl)-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-biphenyl)-methyl imidazole    1-(4-Cyanobenzyl)-5-(1-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-biphenyl)methyl-imidazole    5-(2-[1,1′-Biphenyl]vinylene)-1-(4-cyanobenzyl)imidazole    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)amino]-3-methoxy-4-phenylbenzene    1-(4-Biphenylmethyl)-5-(4-bromophenyloxy)-imidazole    1-(3′-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(4′-Methyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(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    1-(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    1-(4-(2′-Trifluoromethylphenyl)-2-Chlorophenylmethyl)-5-(4-cyanobenzyl) imidazole    1-{1-(4-(2′-trifluoromethylphenyl)phenyl)ethyl}-5-(4-cyanobenzyl) imidazole    1-(2′-Trifluoromethyl-4-biphenylpropyl)-5-(4-cyanobenzyl) imidazole    1-(2′-N-t-Butoxycarbonylamino-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Acetylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Methylsulfonylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Ethylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Phenylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Glycinylaminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl) imidazole    1-(2′-Methyl-4-biphenylmethyl)-2-chloro-5-(4-cyanobenzyl) imidazole    1-(2′-Methyl-4-biphenylmethyl)-4-chloro 5-(4-cyanobenzyl) imidazole    1-(3′-Chloro-2-methyl-4-biphenylmethyl)-4-(4-cyanobenzyl)imidazole    1-(3′-Chloro-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3′-Trifluoromethyl-2-methyl-4-biphenylmethyl)-4-(4-cyanobenzyl) imidazole    1-(3′-Trifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3′-Methoxy-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-Chloro-4′-fluoro-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-Ethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-(2-Propyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-(2-Methyl-2-propyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2′-Ethyl-4-biphenylmethyl)-5-(4-(1H-tetrazol-5-yl))benzyl)imidazole    1-[1-(4-Cyanobenzyl)imidazol-5-ylmethoxy]-4-(2′-methylphenyl)-2-(3-N-phthalimido-1-propyl)benzene    1-(3′,5′-Ditrifluoromethyl-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3′,5′-Chloro-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3′,5′-Dimethyl-2-methyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3-(N-Boc-aminomethyl)-4-biphenylmethyl)-5-(4-cyanobenzyl)-imidazole    1-(3-Aminomethyl-4-biphenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(4-Cyanobenzyl)-2-methyl-5-(2′-methylbiphenyl-4-yloxy)imidazole    5-(4-Cyanobenzyl)-1-(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    1-(3-Butylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole    1-(3-Propylbiphenyl-4-ylmethyl)-5-(4-cyanobenzyl)-imidazole    1-(4-Biphenylmethyl)-4-(4-cyanobenzyl-2-methylimidazole    1-(4-Cyanobenzyl)-5-[(3-fluoro-4-biphenyl)methyl]imidazole    1-(4-Cyanobenzyl)-5-[1-(4-biphenyl)-1-hydroxy]ethyl-2-methylimidazole    1-(4-Cyanobenzyl)-5-(4-biphenylmethyl)-2-methylimidazole    1-(4-Cyanobenzyl)-5-[1-(4-biphenyl)]ethyl-2-methyl imidazole    1-(4-Cyanobenzyl-5-[1-(4-biphenyl)]vinylidene-2-methylimidazole and    1-(4-Cyanobenzyl)-5-[2-(4-biphenyl)]vinylene-2-methylimidazole    1-(4-[Pyrid-2-yl]phenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(4-[3-Methylpyrazin-2-yl]phenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(4-(Pyrimidinyl-5-yl)phenylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-Phenylpyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-Phenyl-N-Oxopyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3-Phenylpyrid-6-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3-Phenyl-N-Oxopyrid-6-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-(3-Trifluoromethoxyphenyl)-pyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-(2-Trifluoromethylphenyl)-pyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3-Phenyl-2-Chloropyrid-6-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(3-Phenyl-4-chloropyrid-6-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-Amino-3-phenylpyrid-6-ylmethyl)-5-(4-cyanobenzyl)imidazole    1-(2-[Pyrid-2-yl]pyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole    N-{1-(4-Cyanobenzyl)-1H-imidazol-5-yl)methyl}-5-(pyrid-2-yl)-2-amino-pyrimidine    N,N-bis(4-Imidazolemethyl)amino-3-[(3-carboxyphenyl)oxy]benzene    N,N-bis(4-Imidazolemethyl)amino-4-[(3-carboxyphenyl)oxy]benzene    N,N-bis(4-Imidazolemethyl)amino-3-[(3-carbomethoxyphenyl)-oxy]benzene    N,N-bis(4-Imidazolemethyl)amino-4-[(3-carbomethoxyphenyl)-oxy]benzene    N-(4-Imidazolemethyl)-N-(4-nitrobenzyl)aminomethyl-3-[(3-carboxyphenyl)oxy]benzene    N-(4-Imidazolemethyl)-N-(4-nitrobenzyl)aminomethyl-3-[(3-carbomethoxyphenyl)oxy]benzene    N-(4-Imidazolemethyl)-N-(4-nitrobenzyl)amino-3-(phenoxy)benzene    N-(4-Imidazolemethyl)-N-(4-nitrobenzyl)amino-4-(phenoxy)benzene    N-(4-Imidazolemethyl)-N-(4-nitrobenzyl)amino-4-(phenylthio)benzene    N-Butyl-N-[1-(4-cyanobenzyl)-5-imidazolemethyl]amino-4-(phenoxy)benzene    N-[1-(4-Cyanobenzyl)-5-imidazolemethyl]amino-4-(phenoxy)benzene    N-(4-Imidazolemethyl)amino-3-[(3-carboxyphenyl)oxy]benzene    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene    (±)-4-[(4-imidazolylmethyl)amino]pentyl-1-(phenoxy)benzene    1-[(N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(n-butyl)amino)methyl]-4-(phenoxy)benzene    4-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(n-butyl)amino]-1-(phenylthio)benzene    (±)4-[N-(1-(4-cyanobenzyl)-4-imidazolylmethyl)-N-(n-butyl)amino]-1-(phenylsulfinyl)benzene    3-[N-(4-imidazolylmethyl)-N-(n-butyl)amino]-N-(phenyl)benzenesulfonamide and    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)amino]-3-methoxy-4-phenylbenzene    4-{3-[4-(-2-Oxo-2-H-pyridin-1-yl)benzyl]-3-H-imidazol-4-ylmethyl}benzonitrile    4-{3-[4-3-Methyl-2-oxo-2-H-pyridin-1-yl)benzyl]-3-H-imidazol-4-ylmethyl}benzonitrile    4-{3-[4-(-2-Oxo-piperidin-1-yl)benzyl]-3-H-imidazol-4-ylmethyl}benzonitrile    4-{3-[3-Methyl-4-(2-oxopiperidin-1-yl)-benzyl]-3-H-imidizol-4-ylmethyl}-benzonitrile    (4-{3-[4-(2-Oxo-pyrrolidin-1-yl)-benzyl]-3H-imidizol-4-ylmethyl}-benzonitrile    4-{3-[4-(3-Methyl-2-oxo-2-H-pyrazin-1-yl)-benzyl]-3-H-imidizol-4-ylmethyl}-benzonitrile    4- {3-[2-Methoxy-4-(2-oxo-2-H-pyridin-1-yl)-benzyl]-3-H-imidizol-4-ylmethyl}-benzonitrile    4-{1-[4-(5-Chloro-2-oxo-2H-pyridin-1-yl)-benzyl]-1H-pyrrol-2-ylmethyl}-benzonitrile    4-[1-(2-Oxo-2H-[1,2′]bipyridinyl-5′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile    4-[1-(5-Chloro-2-oxo-2H-[1,2′]bipyridinyl-5′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile    4-[3-(2-Oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]benzonitrile    4-{3-[1-(3-Chloro-phenyl)-2-oxo-1,2-dihydropyridin-4-ylmethyl]-3H-imidazol-4-ylmethyl}benzonitrile    or a pharmaceutically acceptable salt, disulfide or optical isomer thereof.    
     
     
         11 . The method according to  claim 4  wherein the prenyl-protein transferase inhibitor is selected from: 
 (S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    (R)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone;    4-[1-(5-Chloro-2-oxo-2H-[1,2′]bipyridinyl-5′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile and    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene    or a pharmaceutically acceptable salt, disulfide or optical isomer thereof.    
     
     
         12 . The method according to  claim 4  wherein the antineoplastic agent is paclitaxel and the prenyl-protein transferase inhibitor is 
 2(S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          
     
     
         13 . A method of treating cancer in a mammal in need thereof which comprises administering to said mammal amounts of a prenyl-protein transferase inhibitor and applying to the mammal radiation therapy.  
     
     
         14 . The method according to  claim 13  wherein the amount of a prenyl-protein transferase inhibitor and the radiation therapy are administered simultaneously.  
     
     
         15 . The method according to  claim 13  wherein the amount of a prenyl-protein transferase inhibitor is administered first and the radiation therapy is administered after the prenyl-protein transferase inhibitor has been administered.  
     
     
         16 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is selected from: 
 2(S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    (R)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone;    4-[1-(5-Chloro-2-oxo-2H-[1,2′]bipyridinyl-5′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile and    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene    or a pharmaceutically acceptable salt, disulfide or optical isomer thereof.    
     
     
         17 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is selected from: 
 2(S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          or a pharmaceutically acceptable salt, disulfide or optical isomer thereof.    
     
     
         18 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is: 
 1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    or a pharmaceutically acceptable salt thereof.    
     
     
         19 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is selected from: 
 (R)-1-(3-Chlorophenyl)4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone;    or a pharmaceutically acceptable salt or optical isomer thereof.    
     
     
         20 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is selected from: 
 4-[1-(5-Chloro-2-oxo-2H-[1,2′]bipyridinyl-5′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile and    or a pharmaceutically acceptable salt thereof.    
     
     
         21 . The method according to  claim 13  wherein the prenyl-protein transferase inhibitor is selected from: 
 1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene    or a pharmaceutically acceptable salt thereof.    
     
     
         22 . The method according to  claim 13  which additionally comprises administering to the mammal an amount of an antineoplastic agent.  
     
     
         23 . The method according to  claim 22  wherein the amount of a prenyl-protein transferase inhibitor and the amount of an antineoplastic agent are administered simultaneously.  
     
     
         24 . The method according to  claim 22  wherein the amount of an antineoplastic agent and the amount of a prenyl-protein transferase inhibitor are administered consecutively.  
     
     
         25 . The method according to  claim 22  wherein the prenyl-protein transferase inhibitor is selected from: 
 2(S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone;    (R)-1-(3-Chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone;    4-[1-(5-Chloro-2-oxo-2H-[1,2′]bipyridinyl-5 ′-ylmethyl)-1H-pyrrol-2-ylmethyl]-benzonitrile and    1-[N-(1-(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene    or a pharmaceutically acceptable salt, disulfide or optical isomer thereof.    
     
     
         26 . A pharmaceutical composition for achieving a therapeutic effect in a mammal in need thereof which comprises amounts of at least two therapeutic agents selected from a group consisting of: 
 a) a prenyl-protein transferase inhibitor and    b) an antineoplastic agent.    
     
     
         27 . The pharmaceutical composition according to  claim 26  comprising an amount of a prenyl-protein transferase inhibitor and an amount of an antineoplastic agent.  
     
     
         28 . The pharmaceutical composition according to  claim 26  wherein the therapeutic effect is treatment of cancer.  
     
     
         29 . The pharmaceutical composition according to  claim 26  wherein the therapeutic effect is selected from inhibition of cancerous tumor growth and the regression of cancerous tumors.  
     
     
         30 . The composition according to  claim 27  wherein the antineoplastic agent is paclitaxel and the prenyl-protein transferase inhibitor is 
 2(S)-[2(S)-[2(R)-Amino-3-mercapto]-propylamino-3(S)-methyl]-pentyloxy-3-phenylpropionyl-methionine sulfone isopropyl ester (Compound A)                          
     
     
         31 . A method of preparing a pharmaceutical composition for achieving a therapeutic effect in a mammal in need thereof which comprises mixing amounts of at least two therapeutic agents selected from a group consisting of: 
 a) a prenyl-protein transferase inhibitor and    b) an antineoplastic agent.    
     
     
         32 . The method of preparing a pharmaceutical composition according to  claim 26  comprising mixing an amount of a prenyl-protein transferase inhibitor and an amount of an antineoplastic agent.