Arylmethyl-carbonylamino-thiazole derivatives and their use as antitumor agents

Abstract

A method of modulating apoptosis or treating diseases associated with protein kinases by administering to a mammal in need thereof of an effective amount of 2-amino-1,3-thiazole derivatives represented by formula (I) or (II): where R, R 1 , R 2 and R 3 are as defined herein, or pharmaceutically acceptable salts thereof.

1 .- 21 . (Cancelled).  
     
     
         22 . A method for the modulation of apoptosis comprising administering to a mammal in need thereof an effective amount of a compound represented by formula I or II:  
       
         
           
           
               
               
           
         
       
       wherein 
 L is a phenyl group or a 5 or 6 membered aromatic heterocycle with one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;  
 R is (i) a halogen atom, a nitro group, or it is selected from the group consisting of pyrrolidino, morpholino, piperazino, N-alkyl piperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino and azabicyclo[3.2.2]nonane; or 
 (ii) an amino group optionally further substituted with one or more groups, which may be the same or different, selected from the group consisting of alkyl, aryl, arylalkyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, alkylcarbonyl, arylcarbonyl, and arylalkylcarbonyl, wherein the alkyl moieties therein are optionally further substituted with one or more hydroxy or amino groups; or  
 (iii) a C 3 -C 6  cycloalkyl optionally substituted with a straight or branched C 1 -C 6  alkyl group; or  
 (iv) a straight or branched C 1 -C 6  alkyl group or an arylalkyl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane; or  
 (v) an aryl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane;  
 
 R 1  is a hydrogen atom or a straight or branched C 1 -C 4  alkyl group optionally substituted with one or more hydroxy, alkoxy, amino, alkylamino, or dialkylamino groups;  
 R 2  and R 3 , which may be the same or different, are a hydrogen atom, a cycloalkyl group, a straight or branched C 1 -C 6  alkyl group or an aryl group, which are each optionally substituted as described above for R; or  
 R 2  and R 3 , together with the nitrogen atom to which they are bonded, form a 4-morpholinyl, 1-piperazinyl, N-alkyl-piperazinyl, N-aryl-piperazinyl, N-arylalkyl-piperazinyl, piperidinyl, pyrrolidinyl, 2-oxo-1-pyrrolidinyl, imidazolyl or 3-azabicyclo[3.2.2]nonyl ring;  
 R 4  is carboxy, a perfluorinated alkyl group, a C 2 -C 4  alkynyl group, 2-oxo-pyrrolidinyl, piperidinyl or a straight or branched C 1 -C 6  alkyl group or an aryl group, which is optionally substituted as described above for R;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         23 . The method of  claim 22  wherein said modulation of apoptosis is effectuated to prevent development of AIDS in HIV-infected humans.  
     
     
         24 . The method of  claim 22  wherein 
 L is selected from the group consisting of phenyl, thiazole, imidazole, oxazole, pyrazole, isoxazole, thiophene, pyridine and pyrimidine;    R is (i) a halogen atom, (ii) a group selected from the group consisting of arylamino, alkylamino or dialkylamino, wherein the alkyl moiety is optionally further substituted with one or more hydroxy or amino groups, (iii) a C 3 -C 6  cycloalkyl group optionally substituted with an alkyl group, (iv) a straight or branched C 1 -C 4  alkyl or arylalkyl group, which is optionally substituted as described above, or (v) an optionally substituted aryl group;    R 1  is hydrogen or a C 1 -C 4  alkyl group optionally substituted with a hydroxy or amino group;    or a pharmaceutically acceptable salt thereof.    
     
     
         25 . The method of  claim 22  wherein said compound is selected from the group consisting of 
 N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acrylamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methylpropanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-naphthamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,3,3,3-pentafluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide,    2-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-2-oxoacetic acid;    2-fluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-oxo-beta-alanine;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)malonamide;    4-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-oxo-butanoic acid;    2-[2-(glycoloylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    3-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    3-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    2-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    4-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    4-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-methyl-1-piperazinyl)acetamide;    2-(4-benzyl-1-piperazinyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1-piperidinyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[2-(2-oxo-1-pyrrolidinyl)-1,3-thiazol-4-yl]acetamide;    2-[4-(dimethylamino)phenyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1H-1,2,3,4-tetraazol-1-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-oxo-2-pyrrolidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)succinamide;    3-(1H-benzimidazol-2-yl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-piperidinecarboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    4-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide    2-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)(methyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[3-(dimethylamino)-2-hydroxypropyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2-amino-2-oxoethyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[2-(dimethylamino)-2-oxoethyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(adamantylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(dimethylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-methyl-1-piperazinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-morpholinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-pyrrolidinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    2-{4-[(2,3-dihydroxypropyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2,3-dihydroxypropyl)(methyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[3-(dimethylamino)-2-hydroxypropyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(1-adamantylamino)phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[2-(dimethylamino)-2-oxoethyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(acetylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)nicotinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-thiophenecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-4-isoxazolecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-3,5-dimethyl-4-isoxazolecarboxamide;    (dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(acetylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-1,3-benzodioxole-5-carboxamide;    4-(aminosulfonyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    2-chloro-2,2-difluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-4-piperidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)succinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxy-2-phenylacetamide;    2-[4-(dimethylamino)phenyl]-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-pyridinyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;    2-cyclopropyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-propynamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-1,3-oxazole-4-carboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3,3-dimethylbutanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-methyl-2-butenamide;    3-cyclopentyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,2-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-pyridinylsulfanyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)-1,3-thiazole-4-carboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-cyclopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    N-(5-cyclopropyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide; and pharmaceutically acceptable salts thereof.    
     
     
         26 . The method of  claim 22  wherein said compound is represented by formula I.  
     
     
         27 . The method of  claim 22  wherein said compound is represented by formula II.  
     
     
         28 . A method for the modulation of apoptosis comprising administering to a mammal in need thereof of a pharmaceutical composition comprising 
 (a) an effective amount of a compound represented by formula I or II:                          wherein    L is a phenyl group or a 5 or 6 membered aromatic heterocycle with one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;    R is (i) a halogen atom, a nitro group, or it is selected from the group consisting of pyrrolidino, morpholino, piperazino, N-alkyl piperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino and azabicyclo[3.2.2]nonane; or 
 (ii) an amino group optionally further substituted with one or more groups, which may be the same or different, selected from the group consisting of alkyl, aryl, arylalkyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, alkylcarbonyl, arylcarbonyl, and arylalkylcarbonyl, wherein the alkyl moieties therein are optionally further substituted with one or more hydroxy or amino groups; or  
 (iii) a C 3 -C 6  cycloalkyl optionally substituted with a straight or branched C 1 -C 6  alkyl group; or  
 (iv) a straight or branched C 1 -C 6  alkyl group or an arylalkyl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane; or  
 (v) an aryl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane;  
   R 1  is a hydrogen atom or a straight or branched C 1 -C 4  alkyl group optionally substituted with one or more hydroxy, alkoxy, amino, alkylamino, or dialkylamino groups;    R 2  and R 3 , which may be the same or different, are a hydrogen atom, a cycloalkyl group, a straight or branched C 1 -C 6  alkyl group or an aryl group, which are each optionally substituted as described above for R; or    R 2  and R 3 , together with the nitrogen atom to which they are bonded, form a 4-morpholinyl, 1-piperazinyl, N-alkyl-piperazinyl, N-aryl-piperazinyl, N-arylalkyl-piperazinyl, piperidinyl, pyrrolidinyl, 2-oxo-1-pyrrolidinyl, imidazolyl or 3-azabicyclo[3.2.2]nonyl ring;    R 4  is carboxy, a perfluorinated alkyl group, a C 2 -C 4  alkynyl group, 2-oxo-pyrrolidinyl, piperidinyl or a straight or branched C 1 -C 6  alkyl group or an aryl group, which is optionally substituted as described above for R;    or a pharmaceutically acceptable salt thereof; and    (b) an effective amount of one or more pharmaceutically active agents selected from the group consisting of antibiotic agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cyclooxygenase inhibitors, metallomatixprotase inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angio-genesis agents, farnesyl transferase inhibitors, ras-raf signal transduction pathway inhibitors, cell cycle inhibitors, cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, chemotherapeutic agents and mixtures thereof.    
     
     
         29 . The method of  claim 28  wherein said modulation of apoptosis is effectuated to prevent development of AIDS in HIV-infected humans.  
     
     
         30 . The method of  claim 28  wherein, in said compound of component (a), 
 L is selected from the group consisting of phenyl, thiazole, imidazole, oxazole, pyrazole, isoxazole, thiophene, pyridine and pyrimidine;    R is (i) a halogen atom, (ii) a group selected from the group consisting of arylamino, alkylamino or dialkylamino, wherein the alkyl moiety is optionally further substituted with one or more hydroxy or amino groups, (iii) a C 3 -C 6  cycloalkyl group optionally substituted with an alkyl group, (iv) a straight or branched C 1 -C 4  alkyl or arylalkyl group, which is optionally substituted as described above, or (v) an optionally substituted aryl group; and    R 1  is hydrogen or a C 1 -C 4  alkyl group optionally substituted with a hydroxy or amino group.    
     
     
         31 . The method of  claim 28  wherein the compound of component (a) is selected from the group consisting of 
 N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acrylamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methylpropanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-naphthamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,3,3,3-pentafluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide,    2-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-2-oxoacetic acid;    2-fluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-oxo-beta-alanine;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)malonamide;    4-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-oxo-butanoic acid;    2-[2-(glycoloylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    3-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    3-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    2-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    4-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    4-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-methyl-1-piperazinyl)acetamide;    2-(4-benzyl-1-piperazinyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1-piperidinyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[2-(2-oxo-1-pyrrolidinyl)-1,3-thiazol-4-yl]acetamide;    2-[4-(dimethylamino)phenyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1H-1,2,3,4-tetraazol-1-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-oxo-2-pyrrolidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)succinamide;    3-(1H-benzimidazol-2-yl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2yl)-4-piperidinecarboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    4-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide    2-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)(methyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[3-(dimethylamino)-2-hydroxypropyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2-amino-2-oxoethyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[2-(dimethylamino)-2-oxoethyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(adamantylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(dimethylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-methyl-1-piperazinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-morpholinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-pyrrolidinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-morpholinyl)ethyl]amino}phehenyl)acetamide;    2-{4-[(2,3-dihydroxypropyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2,3-dihydroxypropyl)(methyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[3-(dimethylamino)-2-hydroxypropyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(1-adamantylamino)phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[2-(dimethylamino)-2-oxoethyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(acetylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)nicotinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-thiophenecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino)-2-oxoethyl}phenyl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-4-isoxazolecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-3,5-dimethyl-4-isoxazolecarboxamide;    (dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(acetylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-1,3-benzodioxole-5-carboxamide;    4-(aminosulfonyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    2-chloro-2,2-difluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide; 1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-4-piperidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)succinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxy-2-phenylacetamide;    2-[4-(dimethylamino)phenyl]-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-pyridinyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;    2-cyclopropyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-propynamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-1,3-oxazole-4-carboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3,3-dimethylbutanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-methyl-2-butenamide;    3-cyclopentyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,2-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl-3-(2-thienyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-pyridinylsulfanyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)-1,3-thiazole-4-carboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-cyclopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    N-(5-cyclopropyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide; and    pharmaceutically acceptable salts thereof.    
     
     
         32 . The method of  claim 28  wherein said compound of component (a) is represented by formula I.  
     
     
         33 . The method of  claim 28  wherein said compound of component (a) is represented by formula II.  
     
     
         34 . A method for the treatment of diseases associated with protein kinases selected from the group consisting of protein kinase C, her 2, raf 1, MEK1, MAP kinase, EGF receptor, PDGF receptor IGF receptor, PI3 kinase, weel kinase, Src and Ab1 comprising administering to a mammal in need thereof of a protein kinases treating effective amount of a compound represented by formula I or II:  
       
         
           
           
               
               
           
         
       
       wherein 
 L is a phenyl group or a 5 or 6 membered aromatic heterocycle with one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;  
 R is (i) a halogen atom, a nitro group, or it is selected from the group consisting of pyrrolidino, morpholino, piperazino, N-alkyl piperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino and azabicyclo[3.2.2]nonane; or 
 (ii) an amino group optionally further substituted with one or more groups, which may be the same or different, selected from the group consisting of alkyl, aryl, arylalkyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, alkylcarbonyl, arylcarbonyl, and arylalkylcarbonyl, wherein the alkyl moieties therein are optionally further substituted with one or more hydroxy or amino groups; or  
 (iii) a C 3 -C 6  cycloalkyl optionally substituted with a straight or branched C 1 -C 6  alkyl group; or  
 (iv) a straight or branched C 1 -C 6  alkyl group or an arylalkyl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane; or  
 (v) an aryl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane;  
 
 R 1  is a hydrogen atom or a straight or branched C 1 -C 4  alkyl group optionally substituted with one or more hydroxy, alkoxy, amino, alkylamino, or dialkylamino groups;  
 R 2  and R 3 , which may be the same or different, are a hydrogen atom, a cycloalkyl group, a straight or branched C 1 -C 6  alkyl group or an aryl group, which are each optionally substituted as described above for R; or  
 R 2  and R 3 , together with the nitrogen atom to which they are bonded, form a 4-morpholinyl, 1-piperazinyl, N-alkyl-piperazinyl, N-aryl-piperazinyl, N-arylalkyl-piperazinyl, piperidinyl, pyrrolidinyl, 2-oxo-1-pyrrolidinyl, imidazolyl or 3-azabicyclo[3.2.2]nonyl ring; and  
 R 4 is carboxy, a perfluorinated alkyl group, a C 2 -C 4  alkynyl group, 2-oxo-pyrrolidinyl, piperidinyl or a straight or branched C 1 -C 6  alkyl group or an aryl group, which is optionally substituted as described above for R;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         35 . The method of  claim 34  wherein 
 L is selected from the group consisting of phenyl, thiazole, imidazole, oxazole, pyrazole, isoxazole, thiophene, pyridine and pyrimidine;    R is (i) a halogen atom, (ii) a group selected from the group consisting of arylamino, alkylamino or dialkylamino, wherein the alkyl moiety is optionally further substituted with one or more hydroxy or amino groups, (iii) a C 3 -C 6  cycloalkyl group optionally substituted with an alkyl group, (iv) a straight or branched C 1 -C 4  alkyl or arylalkyl group, which is optionally substituted as described above, or (v) an optionally substituted aryl group; and    R 1  is hydrogen or a C 1 -C 4  alkyl group optionally substituted with a hydroxy or amino group.    
     
     
         36 . The method of  claim 34  wherein said compound is selected from the group consisting of 
 N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acrylamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methylpropanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-naphthamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,3,3,3-pentafluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide,    2-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-2-oxoacetic acid;    2-fluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-oxo-beta-alanine;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)malonamide;    4-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-oxo-butanoic acid;    2-[2-(glycoloylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    3-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    3-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    2-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    4-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    4-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-methyl-1-piperazinyl)acetamide;    2-(4-benzyl-1-piperazinyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1-piperidinyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[2-(2-oxo-1-pyrrolidinyl)-1,3-thiazol-4-yl]acetamide;    2-[4-(dimethylamino)phenyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1H-1,2,3,4-tetraazol-1-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-oxo-2-pyrrolidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thizol-2-yl)succinamide;    3-(1H-benzimidazol-2-yl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-piperidinecarboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    4-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide    2-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)(methyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[3-(dimethylamino)-2-hydroxypropyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2-amino-2-oxoethyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[2-(dimethylamino)-2-oxoethyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(adamantylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(dimethylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-methyl-1-piperazinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-morpholinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-pyrrolidinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    2-{4-[(2,3-dihydroxypropyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2,3-dihydroxypropyl)(methyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[3-(dimethylamino)-2-hydroxypropyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(1-adamantylamino)phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[2-(dimethylamino)-2-oxoethyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(acetylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)nicotinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-thiophenecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl }phenyl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-4-isoxazolecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-3,5-dimethyl-4-isoxazolecarboxamide;    (dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(acetylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-1,3-benzodioxole-5-carboxamide;    4-(aminosulfonyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    2-chloro-2,2-difluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-4-piperdinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)succinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl }phenyl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxy-2-phenylacetamide;    2-[4-(dimethylamino)phenyl]-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-pyridinyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;    2-cyclopropyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-propynamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-1,3-oxazole-4-carboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3,3-dimethylbutanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-methyl-2-butenamide;    3-cyclopentyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thizol-2-yl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,2-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-pyridinylsulfanyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)-1,3-thiazole-4-carboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-cyclopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    N-(5-cyclopropyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide; and    pharmaceutically acceptable salts thereof.    
     
     
         37 . The method of  claim 34  wherein said compound is represented by formula I.  
     
     
         38 . The method of  claim 34  wherein said compound is represented by formula II.  
     
     
         39 . A method for the treatment of diseases associated protein kinases selected from the group consisting of protein kinase C, her 2, raf 1, MEK1, MAP kinase, EGF receptor, PDGF receptor, IGF receptor, PI3 kinase, weel kinase, Src and Ab1 comprising administering to a mammal in need thereof of a protein kinase treating effective amount of a pharmaceutical composition comprising 
 (a) an effective amount of a compound represented by formula I or II:                          wherein    L is a phenyl group or a 5 or 6 membered aromatic heterocycle with one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;    R is (i) a halogen atom, a nitro group, or it is selected from the group consisting of pyrrolidino, morpholino, piperazino, N-alkyl piperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino and azabicyclo[3.2.2]nonane; or 
 (ii) an amino group optionally further substituted with one or more groups, which may be the same or different, selected from the group consisting of alkyl, aryl, arylalkyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, alkylcarbonyl, arylcarbonyl, and arylalkylcarbonyl, wherein the alkyl moieties therein are optionally further substituted with one or more hydroxy or amino groups; or  
 (iii) a C 3 -C 6  cycloalkyl optionally substituted with a straight or branched C 1 -C 6  alkyl group; or  
 (iv) a straight or branched C 1 -C 6  alkyl group or an arylalkyl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane; or  
 (v) an aryl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C 1 -C 6  alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, alkyl-C 3 -C 6  cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane;  
   R 1  is a hydrogen atom or a straight or branched C 1 -C 4  alkyl group optionally substituted with one or more hydroxy, alkoxy, amino, alkylamino, or dialkylamino groups;    R 2  and R 3 , which may be the same or different, are a hydrogen atom, a cycloalkyl group, a straight or branched C 1 -C 6  alkyl group or an aryl group, which are each optionally substituted as described above for R; or    R 2  and R 3 , together with the nitrogen atom to which they are bonded, form a 4-morpholinyl, 1-piperazinyl, N-alkyl-piperazinyl, N-aryl-piperazinyl, N-arylalkyl-piperazinyl, piperidinyl, pyrrolidinyl, 2-oxo-1-pyrrolidinyl, imidazolyl or 3-azabicyclo[3.2.2]nonyl ring;    R 4  is carboxy, a perfluorinated alkyl group, a C 2 -C 4  alkynyl group, 2-oxo-pyrrolidinyl, piperidinyl or a straight or branched C 1 -C 6  alkyl group or an aryl group, which is optionally substituted as described above for R;    or a pharmaceutically acceptable salt thereof; and    (b) an effective amount of one or more pharmaceutically active agents selected from the group consisting of antibiotic agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cycloxygenase inhibitors, metallomatrixprotase inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angiogenesis agents, farnesyl transferase inhibitors, ras-raf signal transdiction pathway inhibitors, cell cycle inhibitors, calks inhibitors, tribulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, chemotherapeutic agents and mixtures thereof.    
     
     
         40 . The method of  claim 39  wherein, in said compound of component (a), 
 L is selected from the group consisting of phenyl, thiazole, imidazole, oxazole, pyrazole, isoxazole, thiophene, pyridine and pyrimidine;    R is (i) a halogen atom, (ii) a group selected from the group consisting of arylamino, alkylamino or dialkylamino, wherein the alkyl moiety is optionally further substituted with one or more hydroxy or amino groups, (iii) a C 3 -C 6  cycloalkyl group optionally substituted with an alkyl group, (iv) a straight or branched C 1 -C 4  alkyl or arylalkyl group, which is optionally substituted as described above, or (v) an optionally substituted aryl group; and    R 1  is hydrogen or a C 1 -C 4  alkyl group optionally substituted with a hydroxy or amino group.    
     
     
         41 . The method of  claim 39  wherein said compound of component (a) is selected from the group consisting of 
 N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acrylamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-methylpropanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-naphthamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,3,3,3-pentafluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide,    2-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-2-oxoacetic acid;    2-fluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-oxo-beta-alanine;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)malonamide;    4-[(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-oxo-butanoic acid;    2-[2-(glycoloylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    3-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    3-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    2-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl)}-1,3-thiazol-2-yl)acetamide;    4-hydroxy-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    4-amino-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-methyl-1-piperazinyl)acetamide;    2-(4-benzyl-1-piperazinyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-2-(1-piperidinyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[2-(2-oxo-1-pyrrolidinyl)-1,3-thiazol-4-yl]acetamide;    2-[4-(dimethylamino)phenyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(1H-1,2,3 ,4-tetraazol-1-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-oxo-2-pyrrolidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)succinamide;    3-(1H-benzimidazol-2-yl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-4-piperidinecarboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    4-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)butanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide    2-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-methyl-1-piperazinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-methyl-1-piperzinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-{methyl[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-4-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2,3-dihydroxypropyl)(methyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[3-(dimethylamino)-2-hydroxypropyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{2-[(2-amino-2-oxoethyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(2-{[2-(dimethylamino)-2-oxoethyl]amino}-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(adamantylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(dimethylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-methyl-1-piperazinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(4-morpholinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-( 1-pyrrolidinyl)phenyl]acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-methyl-1-piperazinyl)ethyl]amino}phenyl)acetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{[2-(4-morpholinyl)ethyl]amino}phenylacetamide;    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-{methyl[2-(4-morpholinyl)ethyl]amino}phenyl)acetamide;    2-{4-[(2,3-dihydroxypropyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2,3-dihydroxypropyl)(methyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[3-(dimethylamino)-2-hydroxypropyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(1-adamantylamino)phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-(4-{[2-(dimethylamino)-2-oxoethyl]amino}phenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    2-[4-(acetylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)nicotinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-thiophenecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-5-methyl-4-isoxazolecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-3,5-dimethyl-4-isoxazolecarboxamide;    (dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(acetylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    4-(dimethylamino)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-1,3-benzodioxole-5-carboxamide;      4 -(aminosulfonyl)-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)benzamide;    2-chloro-2,2-difluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    2-cyano-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide;    1-acetyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-4-piperidinecarboxamide;    N′1′-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)succinamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxyacetamide;    3,3,3-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-phenylacetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-methoxy-2-phenylacetamide;    2-[4-(dimethylamino)phenyl]-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)acetamide    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-pyridinyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenyl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;    2-cyclopropyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl-2-propynamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-5-methyl-1,3-oxazole-4-carboxamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl-3,3-dimethylbutanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-methyl-2-butenamide;    3-cyclopentyl-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide;    2,2,2-trifluoro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(4-pyridinylsulfanyl)acetamide;    N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)-2-(3-pyridinyl)-1,3-thiazole-4-carboxamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-(5-cyclopropyl-1,3-thiazol-2-yl)acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(2-hydroxyethyl)(methyl)amino]-1,3-thiazol-2-yl}acetamide;    2-[4-(dimethylamino)phenyl]-N-{5-[(3-hydroxypropyl)(methyl)amino]-1,3-thiazol-2-yl}acentamide;    N-(5-cyclopropyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide; and    pharmaceutically acceptable salts thereof.    
     
     
         42 . The method of  claim 39  wherein said compound of component (a) is represented by formula I.  
     
     
         43 . The method of  claim 39  wherein said compound of component (a) is represented by formula II.