3-Mercaptopyrrolidines as farnesyl protein transferase inhibitors

Abstract

The present invention relats to inhibitors of ras farnesylation of Formula (I) wherein: R 1 is for example H and further values as defined in the specification; R 2 is for example H and further values as defined in the specification; R 3 is for example H or a substituent having values as defined in the specification; p is 0-3 in which R 3 values can be the same or different; L is a linking moiety for example —CH 2 —NH— and further values as defined in the specification; A is selected from phenyl; naphthyl; a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms where the heteroatoms are independently selected from O, N and S; or a —S—S— dimer thereof when R 2 =H; or a N-oxide or a pharmaceutically-acceptable salt, prodrug or solvate thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use is in cancer therapy.

1 - 13 . (canceled)  
     
     
         14 . A compound of formula III:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X 1  is selected from H; C 1-6 alkyl; hydroxyC 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl; C 1-6 alkylcarbonyl; hydroxyC 1-6 alkylcarbonyl; C 1-6 alkoxyC 1-6 alkylcarbonyl;  
 A is selected from phenyl, naphthyl or a 5-10 membered heterocyclic ring having up to 5 heteroatoms selected from O, N and S;  
 X 2  is selected from H; phenyl; phenylC 1-6 alkyl; a 5-6 membered heteroaryl ring containing up to 3 heteroatoms selected from O, N and S optionally linked to A by C 1-6 alkyl; and  
 X 2 is optionally substituted on any ring by R a  and/or R b  and R a  and R b  are independently selected from C 1-4 alkyl, halogen, hydroxy, C 1-4 alkoxy, C 1-4 alkanoyl, C 1-4 alkanoyloxy, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkanoylamino, nitro, cyano, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, thiol, C 1-4 alkylsulfanyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl and sulfonamido;  
 X 3  is selected from H; C 1-6 alkyl;  
 X 4  is selected from C 1-6 alkylsulfanyl; C 1-6 alkylsulfinyl; C1 6alkylsulfonyl; carbamoyl; N-(C 1-6 alkyl)carbamoyl; N-(diC 1-6 alkyl)carbamoyl; and hydroxy or a C 1-4 alkyl ether thereof;  
 or a N-oxide, or a pharmaceutically-acceptable salt, prodrug or solvate thereof.  
 
     
     
         15 . A compound according to  claim 14  wherein 
 X 1  is selected from H and C 1-6 alkoxyC 1-6 alkyl;    X 2  is selected from H; phenyl and phenylC 1-6 alkyl;    X 4  is C 1-6 alkylsulfanyl; and    A is selected from phenyl and naphthyl.    
     
     
         16 . A compound according to  claim 14  wherein: 
 X 1  is H or methoxyC 1-4 alkyl;    X 2  is H, phenyl, benzyl, phenethyl, 4-methylphenethyl or 4-methylphenylacetylene;    X 3  is H or C 1-4 alkyl;    X 4  is C 1-4 alkylsulfanyl; and    A is phenyl.    
     
     
         17 . A compound according to  claim 14 , wherein the chiral carbon to which —COOX 3  is attached is in S configuration.  
     
     
         18 . A compound according to  claim 14 , wherein the chiral carbon atoms at the 2 and 3 positions of the pyrrolidine ring are in the R configuration.  
     
     
         19 . A compound of formula (IV):  
       
         
           
           
               
               
           
         
       
       wherein: 
 X 5  is selected from C 1-4 alkyloxyC 1-4 alkyl; —C 1-4 alkylPh; —CO—C 1-4 alkyl-Ph; —CO—C 1-6 alkyl; —CO—C 1-4 alkyl-heteroaryl where heteroaryl is a 5-10 membered heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and Ph or heteroaryl are optionally substituted by R a  and/or R b  and R a  and R b  are independently selected from C 1-4 alkyl, halogen, hydroxy, C 1-4 alkoxy, C 1-4 alkanoyl, C 1-4 alkanoyloxy, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkanoylamino, nitro, cyano, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, thiol, C 1-4 alkylsulfanyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl and sulfonamido;  
 A is naphthyl or a 10 membered heteroaryl ring having up to 5 heteroatoms selected from O, N and S;  
 R 3  is selected from H; OH; CN; CF 3 ; NO 2 ; —C 1-4 alkyl; —C 1-4 alkylene-R 7 ; —C 2-4 alkenylene-R 7 ; —C 2-4 alkynylene-R 7 ; R 7 ; OR 7  (where R 7  is selected from phenyl, naphthyl, a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and any aryl ring in R 7  is optionally substituted by R a  and/or R b ); C 2-4 alkenyl; halogen; —(CH 2 ) n COOR 8  (where n 1 =0-3 and R 8  represents H, C 1-4 alkyl, or C 2-4 alkenyl); —CONR 9 R 10  (where R 9  and R 10  independently represent H, C 1-4 alkyl, C 2-4 alkenyl, —O—C 1-4 alkyl, —O—C 2-4 alkenyl or —C 1-3 alkylenePh (wherein Ph is optionally substituted by R a  and R b  as defined above); —CON(R 11 )OR 12  (where R 11  and R 12  independently represent H, C 1-4 alkyl or C 2-4 alkenyl); 
 a group of Formula II:  
   —CONR 13 —CR 13a R 14 —COOR 17 , 
  (where R 13  and R 13a  are independently H or C 1-4 alkyl, R 17  is H or C 1-6 alkyl, R 14  is selected from the side chain of a lipophilic amino acid, carbamoylC 1-4 alkyl, N-(monoC 1-4 alkyl)carbamoylC 1-4 alkyl and N-(diC 1-4 alkyl)carbamoylC 1-4 alkyl) the group of Formula II having L or D configuration at the chiral alpha carbon in the corresponding free amino acid;  
 a lactone of formula:  
                     
 C 1-4 alkyl monosubstituted on carbon with ═N—OH;  
 a group of Formula -X-R 15  (where X is selected from O, CO, CH 2 , S, SO, SO 2  and R 15  is selected from C 1-6 alkyl, phenyl, naphthyl, a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and any aryl ring in R 15  is optionally substituted by R a  and/or R b ;  
 
 p is 0-3 in which R 3  values can be the same or different;  
 or a N-oxide or a pharmaceutically-acceptable salt, prodrug or solvate thereof.  
 
     
     
         20 . A compound of Formula IV according to  claim 19 , wherein: 
 X 5  is pyridylmethylcarbonyl, thiazolylcarbonyl, 1-oxoidopyridylcarbonyl, —CO—C 1-4 alkyl or —CH 2 -Ph-O—C 1-4 alkyl;    A is phenyl or naphthyl; and    p is 0.    
     
     
         21 . A compound according to  claim 19 , wherein the chiral carbons at the 2 and 3 positions of the pyrrolidine ring are in the R configuration.  
     
     
         22 . A compound of formula (V):  
       
         
           
           
               
               
           
         
       
       wherein: 
 X 6  is selected from C 1-4 alkyloxyC 1-4 alkyl; —C 1-4 alkylPh; —CO—C 1-4 alkyl-Ph; —CO—C 1-6 alkyl; —CO—C 1-4 alkyl-heteroaryl where heteroaryl is a 5-10 membered heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and Ph or heteroaryl are optionally substituted by R a  and/or R b  and R a  and R b  are independently selected from C 1-4 alkyl, halogen, hydroxy, C 1-4 alkoxy, C 1-4 alkanoyl, C 1-4 alkanoyloxy, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkanoylamino, nitro, cyano, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, thiol, C 1-4 alkylsulfanyl, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl and sulfonamido;  
 X 7  is Ph optionally substituted by R a  and/or R b ;  
 A is Ph or naphthyl or a 5-10 membered heteroaryl ring having up to 5 heteroatoms selected from O, N and S;  
 R 3  is selected from H; OH; CN; CF 3 ; NO 2 ; —C 1-4 alkyl; —C 1-4 alkylene-R 7 ; —C 2-4 alkenylene-R 7 ; —C 2-4 alkynylene-R 7 ; R 7 ; OR 7  (where R 7  is selected from phenyl, naphthyl, a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and any aryl ring in R 7  is optionally substituted by R a  and/or R b ); C 2-4 alkenyl; halogen; —(CH 2 ) n COOR 8  (where n 1 =0-3 and R 8  represents H, C 1-4 alkyl, or C 2-4 alkenyl); —CONR 9 R 10  (where R 9  and R 10  independently represent H, C 1-4 alkyl, C 2-4 alkenyl, —O—C 1-4 alkyl, —O—C 2-4 alkenyl or —C 1-3 alkylenePh (wherein Ph is optionally substituted by R a  and R b  as defined above); —CON(R 11 )OR 12  (where R 11  and R 12  independently represent H, C 1-4 alkyl or C 2-4 alkenyl); 
 a group of Formula II:  
   —CONR 13 —CR 13a R 14 —COOR 17 , 
  (where R 13  and R 13a  are independently H or C 1-4 alkyl, R 17  is H or C 1-6 alkyl, R 14  is selected from the side chain of a lipophilic amino acid, carbamoylC 1-4 alkyl, N-(monoC 1-4 alkyl)carbamoylC 1-4 alkyl and N-(diC 1-4 alkyl)carbamoylC 1-4 alkyl) the group of Formula II having L or D configuration at the chiral alpha carbon in the corresponding free amino acid;  
 a lactone of formula:  
                     
 C 1-4 alkyl monosubstituted on carbon with ═N—OH;  
 a group of Formula -X-R 15  (where X is selected from O, CO, CH 2 , S, SO, SO 2  and R 15  is selected from C 1-6 alkyl, phenyl, naphthyl, a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms selected from O, N and S and any aryl ring in R 15  is optionally substituted by R a  and/or R b ;  
 
 p is 0-3 in which R 3  values can be the same or different;  
 or a N-oxide, or a pharmaceutically acceptable salt, pro-drug or solvate thereof.  
 
     
     
         23 . A compound of Formula V according to  claim 22 , wherein: 
 X 6  is pyridylmethylcarbonyl, thiazolylcarbonyl, 1-oxoidopyridylcarbonyl, —CO—C 1-4 alkyl or —CH 2 -Ph-O—C 1-4 alkyl;    X 7  is phenyl;    A is phenyl or naphthyl; and    p is 0.    
     
     
         24 . A compound according to  claim 22 , wherein the chiral carbons at the 2 and 3 positions of the pyrrolidine ring are in the R configuration.  
     
     
         25 . A compound which is any one of the following individual compounds or a pharmaceutically acceptable salt thereof: 
 (2S)-2-{2-benzyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-benzyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-({2-phenyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({2-phenyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)amino]-naphthalene-1-carbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({3-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)amino]-naphthalene-1-carbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-({-3-phenyl-5[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({-3-phenyl-5[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-{3-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-(3-methoxy-propyl)-amino]-benzoylamino}-4-methylsulfanyl-butyric acid;    (2S)-4-carbamoyl-2-({2-phenyl-5-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-butyric acid;    (2S)-4-carbamoyl-2-({2-phenyl-5-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-butyric acid methyl ester;    (2S)-2-{2-benzyl-4-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)amino]-benzoylamino}-4-methylsulfanyl-butyric acid;    (2S)-2-(2-methoxy-ethyl)-1-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-4-naphthoyl-piperazine;    (2S)-2-{2-benzyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)amino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-benzyl-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)amino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-phenethyl-5-[(trans)-3-sulfanylpyrrolidin-2-ylmethylaminobenzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-phenethyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-benzyl-5-[(trans)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-(4-methylphenylethynyl)-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-{2-benzyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid isopropyl ester;    (2S)-2-{2-benzyl-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-benzyl-4-[(trans)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-benzyl-5-[(trans)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-phenyl-5-[(trans)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-phenyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-benzyl-5-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-(4-methylphenethyl)-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-(4-methylphenylethynyl)-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)amino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-[2-(4-fluorophenethyl)-4-[(cis)-3-sulfanyl)-pyrrolidin-2-ylmethylamino)-benzoylamino]-4-methylsulfanylbutyric acid;    methyl(2S)-2-[2-(4-fluorophenethyl)-4-[(cis)-3-sulfanylpyrrolidin-2-ylmethylamino)-benzoylamino]-4-methylsulfanylbutyrate;    (2S)-2-[2-(4-fluorophenethyl)-4-((2R,3R)-3-sulfanyl-pyrrolidin-2-ylmethylamino)-benzoylamino]-4-methylsulfanylbutyric acid;    (2S)-2-{2-Benzyl-5-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-benzoylamino}-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-{2-Benzyl-5-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-benzoylamino}-4-methylsulfanylbutyric acid;    (2S)-2-({2-phenyl-5-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({2-phenyl-5-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-({3-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-naphthalene-1-carbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({3-[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-naphthalene-1-carbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-({-3-phenyl-5[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid methyl ester;    (2S)-2-({-3-phenyl-5[([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-4-methylsulfanylbutyric acid;    (2S)-2-{3-[([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-(3-methoxy-propyl)-amino]-benzoylamino}-4-methylsulfanyl-butyric acid;    (2S)-4-carbamoyl-2-({2-phenyl-5-[([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-butyric acid;    (2S)-4-carbamoyl-2-({2-phenyl-5-[([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-amino]-phenylcarbonyl}-amino)-butyric acid methyl ester;    (2S)-2-{2-benzyl-4-[([2R,3R]3-sulfanyl-pyrrolidin-2-ylmethyl)-amino]-benzoylamino}-4-methylsulfanyl-butyric acid;    (2S)-2-[2-(4-Fluorophenethyl)-5-([2R,3R]-3-sulfanylpyrrolidin-2-ylmethylamino)-benzoylamino]-4-methylsulfanylbutyric acid;    (cis)-2-[{N-(4-methoxybenzyl)-N-(naphthalen-1-ylmethylamino}-methyl]-pyrrolidine-3-thiol;    N-(naphthalen-1-ylmethyl)-N-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)-pentanamide;    N-(naphthalen-1-ylmethyl)-N-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)-2-(pyridin-3-yl)-acetamide;    N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3-methyl-N-(2-naphthalen-1-yl-ethyl)butyramide;    N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-N-(2-naphthalen-1-yl-ethyl)-2-pyridin-3-yl-acetamide;    (cis)-2-{[(3-methoxypropyl)-(2-naphthalen-1-ylethyl)amino]methyl}-pyrrolidine-3-thiol;    N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-2-(4-methoxy-phenyl)-N-(2-naphthalen-2-ylethyl)-acetamide;    (cis)-2-{[(2-(4-methoxyphenyl)ethyl)-(2-naphthalen-1-ylethyl)amino]methyl}-pyrrolidine-3-thiol;    N-(2,2-diphenyl-ethyl)-N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3-methyl-butyramide;    N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-N-(2-naphthalen-2-yl-ethyl)-butyramide;    N-(2,2-diphenyl-ethyl)-N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-butyramide;    N-[(cis)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-N-(2-naphthalen-1-yl-ethyl)-butyramide;    N-(naphthyl-1-yl-ethyl)-N-[(cis)-3-sulfanylpyrrolidin-2yl-methyl)-thiazole-5-carboxamide;    6-methoxy-1-oxido-N-(naphthyl-1-yl-ethyl)-N-[cis)-3-sulfanylpyrrolidin-2-ylmethyl]-pyridine-3-carboxamide;    (cis)-2-[N-isovaleryl-N-(2-(napth-1-yl)ethyl)aminiomethyl]-3-sulfanylpyrrolidine;    (cis)-2-[N-(3-pyridylacetyl)-N-(naphth-1-yl)ethyl)aminomethyl]-3-sulfanylpyrrolidine;    (cis)-2-[N-1-oxido-6-methoxypyridin-3-ylcarbonyl)-N-(naphth-1-yl)ethyl)aminomethyl]-3-sulfanylpyrrolidine;    (cis)-2-[N-thiazol-5-ylcarbonyl)-N-(naphth-1-yl)ethyl)aminomethyl]-3-sulfanylpyrrolidine;    (2R,3R)-2-[{N-(4-methoxybenzyl)-N-(naphthalen-1-ylmethyl)-amino}-methyl]-pyrrolidine-3-thiol;    N-(naphthalen-1-ylmethyl)-N-([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-pentanamide;    N-(naphthalen-1-ylmethyl)-N-([2R,3R]-3-sulfanylpyrrolidin-2-ylmethyl)-2-(pyridin-3-yl)-acetamide;    N-((2R,3R)-3-sulfanyl-pyrrolidin-2-ylmethyl)-3-methyl-N-(2-naphthalen-1-yl-ethyl)butyramide;    N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-N-(2-naphthalen-1-yl-ethyl)-2-pyridin-3-yl-acetamide;    (2R,3R)-2-{[(3-Methoxypropyl)-(2-naphthalen-1-ylethyl)amino]methyl}-pyrrolidine-3-thiol;    N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-2-(4-methoxy-phenyl)-N-(2-naphthalen-2-yl-ethyl)-acetamide;    (2R,3R)-2-{[(2-(4-Methoxyphenyl)ethyl)-(2-naphthalen-1-ylethyl)amino]methyl}-pyrrolidine-3-thiol;    N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-N-(2-naphthalen-2-yl-ethyl)-butyramide;    N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-N-(2-naphthalen-1-yl-ethyl)-butyramide;    6-methoxy-1-oxido-N-(2,2-diphenyl-ethyl)-N-((2R,3R)-3-sulfanylpyrrolidin-2-ylmethyl)-pyridine-3-carboxamide;    N-(naphthyl-1-yl-ethyl)-N-([2R,3R]-3-sulfanylpyrrolidin-2yl-methyl)-thiazole-5-carboxamide;    6-methoxy-1-oxido-N-(naphthyl-1-yl-ethyl)-N-((2R,3R)-3-sulfanylpyrrolidin-2-ylmethyl)-pyridine-3-carboxamide;    2-(3-pyridyl)-N-(2,2-diphenyl-ethyl)-N-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl)-acetamide;    6-methoxy-1-oxido-N-(2,2-diphenyl-ethyl)-N-[(cis)-3-sulfanylpyrrolidin-2-ylmethyl]-pyridine-3-carboxamide;    N-(2,2-Diphenyl-ethyl)-N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-3-methyl-butyramide;    N-(2,2-Diphenyl-ethyl)-N-([2R,3R]-3-sulfanyl-pyrrolidin-2-ylmethyl)-3,3-dimethyl-butyramide; and    2-(3-pyridyl)-N-(2,2-diphenyl-ethyl)-N-((2R,3R)-3-sulfanylpyrrolidin-2-ylmethyl)-acetamide.    
     
     
         26 . A pharmaceutical composition which comprises a compound according to  claim 14  and a pharmaceutical-acceptable carrier.  
     
     
         27 . A pharmaceutical composition which comprises a compound according to  claim 19  and a pharmaceutically-acceptable carrier.  
     
     
         28 . A pharmaceutical composition which comprises a compound according to  claim 22  and a pharmaceutically-acceptable carrier.  
     
     
         29 . A pharmaceutical composition which comprises a compound according to  claim 25  and a pharmaceutically-acceptable carrier.  
     
     
         30 . A process for preparing compounds of the Formula III as defined in  claim 14  which comprises deprotecting a compound of Formula VI:  
       
         
           
           
               
               
           
         
       
       wherein X 8  represents the right hand side of the Formula III as defined in  claim 14 , Pr 1  is H or an amino protecting group, Pr 2  is H or a thio protecting group and any functional groups in X 8  are optionally protected with the proviso that there is at least one protecting group and optionally converting the product thus obtained into a pharmaceutically-acceptable salt thereof.  
     
     
         31 . A process for preparing compounds of the Formula IV as defined in  claim 19  which comprises deprotecting a compound of Formula VI:  
       
         
           
           
               
               
           
         
       
       wherein X 8  represents the right hand side of the Formula IV as defined in  claim 19 , Pr 1  is H or an amino protecting group, Pr 2  is H or a thio protecting group and any functional groups in X 8  are optionally protected with the proviso that there is at least one protecting group and optionally converting the product thus obtained into a pharmaceutically-acceptable salt thereof.  
     
     
         32 . A process for preparing compounds of the Formula V as defined in  claim 22  which comprises deprotecting a compound of Formula VI:  
       
         
           
           
               
               
           
         
       
       wherein X 8  represents the right hand side of the Formula V as defined in  claim 22 , Pr 1  is H or an amino protecting group, Pr 2  is H or a thio protecting group and any functional groups in X 8  are optionally protected with the proviso that there is at least one protecting group and optionally converting the product thus obtained into a pharmaceutically-acceptable salt thereof.  
     
     
         33 . A method of treating a disease or medical condition mediated through farnesylation of CAAX-containing proteins which comprises administering to a warm-blooded animal an effective amount of a compound according to  claim 14 ,  19 ,  22  or  25 , wherein said disease or medical condition is carcinoma of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid or skin.  
     
     
         34 . A method of treating a disease or medical condition mediated through farnesylation of CAAX-containing proteins which comprises administering to a warm-blooded animal an effective amount of a compound according to  claim 14 ,  19 ,  22  or  25 , wherein said disease or medical condition is a hematopoietic tumor of lymphoid lineage selected from acute lymphocytic leukaemia, B-cell lymphoma and Burketts lymphoma.  
     
     
         35 . A method of treating a disease or medical condition mediated through farnesylation of CAAX-containing proteins which comprises administering to a warm-blooded animal an effective amount of a compound according to  claim 14 ,  19 ,  22  or  25 , wherein said disease or medical condition is a hematopoietic tumor of myeloid lineage selected from acute or chronic myelogenous leukemias and promyelocytic leukaemia.  
     
     
         36 . A method of treating a disease or medical condition mediated through farnesylation of CAAX-containing proteins which comprises administering to a warm-blooded animal an effective amount of a compound according to  claim 14 ,  19 ,  22  or  25 , wherein said disease or medical condition is a tumor of mesenchymal origin selected from fibrosarcoma and rhabdomyosarcoma.  
     
     
         37 . A method of treating a disease or medical condition mediated through farnesylation of CAAX-containing proteins which comprises administering to a warm-blooded animal an effective amount of a compound according to  claim 14 ,  19 ,  22  or  25 , wherein said disease or medical condition is a tumor selected from melanoma, seminoma, teratocarcinoma, neuroblastoma and glioma.