Thienopyrimidine derivatives, a process for their preparation and pharmaceutical compositions containing them

Abstract

Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 12 , X, A and n are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.

1 . A method of treating a condition selected from cancer of the bladder, cancer of the uterus, cancer of the colon, cancer of the esophagus, cancer of the liver, ovarian cancer, prostate cancer, pancreatic cancer, auto-immune diseases, and diseases of the immune system, in a subject in need thereof, comprising administration of an effective amount of compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 A represents linear or branched (C 1 -C 6 )alkyl, linear or branched (C 2 -C 6 )alkenyl, linear or branched (C 2 -C 6 )alkynyl, linear or branched (C 1 -C 6 )alkoxy, —S—(C 1 -C 6 )alkyl, linear or branched (C 1 -C 6 )polyhaloalkyl, hydroxy, cyano, —NR 10 R 10 ′, -Cy 6 , or halogen; 
 R 1 , R 2 , R 3 , R 4  and R 5  independently of one another represent hydrogen, halogen, linear or branched (C 1 -C 6 )alkyl, linear or branched (C 2 -C 6 )alkenyl, linear or branched (C 2 -C 6 )alkynyl, linear or branched (C 1 -C 6 )polyhaloalkyl, hydroxy, linear or branched (C 1 -C 6 )alkoxy, —S—(C 1 -C 6 )alkyl, cyano, nitro, -alkyl(C 0 -C 6 )—NR 8 R 8 ′, —O-Cy 1 , -alkyl(C 0 -C 6 )-Cy 1 , -alkenyl(C 2 -C 6 )-Cy 1 , -alkynyl(C 2 -C 6 )-Cy 1 , —O-alkyl(C 1 -C 6 )—R 9 , —C(O)—OR 8 , —O—C(O)—R 8 , —C(O)—NR 8 R 8 ′, —NR 8 —C(O)—R 8 ′, —NR 8 —C(O)—OR 8 ′, -alkyl(C 1 -C 6 )—NR 8 —C(O)—R 8 ′, —SO 2 —NR 8 R 8 ′, or —SO 2 -alkyl(C 1 -C 6 ), 
 or the substituents of one of the pairs (R 1 , R 2 ), (R 2 , R 3 ), (R 1 , R 3 ), (R 4 , R 5 ) when grafted onto two adjacent carbon atoms, together with the carbon atoms carrying them, form an aromatic or non-aromatic ring having from 5 to 7 ring members, which ring may have from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen, and which ring may be optionally substituted by a group selected from linear or branched (C 1 -C 6 )alkyl, —NR 10 R 10 ′, -alkyl(C 0 -C 6 )-Cy 1 , and oxo; 
 X represents a carbon or a nitrogen atom; 
 R 6  represents hydrogen, linear or branched (C 1 -C 8 )alkyl, aryl, heteroaryl, arylalkyl(C 1 -C 6 ), heteroarylalkyl(C 1 -C 6 ); 
 R 7  represents linear or branched (C 1 -C 6 )alkyl, linear or branched (C 2 -C 6 )alkenyl, linear or branched (C 2 -C 6 )alkynyl, -Cy 3 , -alkyl(C 1 -C 6 )-Cy 3 , -alkenyl(C 2 -C 6 )-Cy 3 , -alkynyl(C 2 -C 6 )-Cy 3 , -Cy 3 -Cy 4 , -alkynyl(C 2 -C 6 )—O-Cy 3 , -Cy 3 -alkyl(C 0 -C 6 )—O-alkyl(C 0 -C 6 )-Cy 4 , halogen, cyano, —C(O)—R 11 , or —C(O)—NR 11 R 11 ′; 
 R 8  and R 8 ′ independently of one another represent hydrogen, linear or branched (C 1 -C 6 )alkyl, or -alkyl(C 0 -C 6 )-Cy 1 , 
 or (R 8 , R 8 ′), together with the nitrogen atom carrying them, form an aromatic or non-aromatic ring having from 5 to 7 ring members, which ring may have, in addition to the nitrogen atom, from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen, wherein the nitrogen in question may be substituted by hydrogen, or linear or branched (C 1 -C 6 )alkyl and wherein one or more of the carbon atoms of the possible substituents, may be deuterated; 
 R 9  represents -Cy 1 , -Cy 1 -alkyl(C 0 -C 6 )-Cy 2 , -Cy 1 -alkyl(C 0 -C 6 )—O-alkyl(C 0 -C 6 )-Cy 2 , -Cy 1 -alkyl(C 0 -C 6 )—NR 8 -alkyl(C 0 -C 6 )-Cy 2 , -Cy 1 -Cy 2 -O-alkyl(C 0 -C 6 )-Cy 5 , —NR 8 R 8 ′, —C(O)—NR 8 R 8 ′, —OR 8 , —NR 8 —C(O)—R 8 ′, —O-alkyl(C 1 -C 6 )—OR 8 , —SO 2 —R 8 , —C(O)—OR 8 , or —NH—C(O)—NH—R 8 ; 
 R 10 , R 10 ′, R H  and R u ′ independently of one another represent hydrogen or optionally substituted linear or branched (C 1 -C 6 )alkyl; 
 R 12  represents hydrogen or hydroxy; 
 Cy 1 , Cy 2 , Cy 3 , Cy 4 , Cy 5  and Cy 6  independently of one another, represent cycloalkyl, heterocycloalkyl, aryl or heteroaryl; 
 n is an integer equal to 0 or 1; 
 
         it being understood that:
 “aryl” means a phenyl, naphthyl, biphenyl, indanyl, or indenyl; 
 “heteroaryl” means any mono- or bi-cyclic group having from 5 to 10 ring members, having at least one aromatic moiety and having from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen; 
 “cycloalkyl” means any mono- or bi-cyclic non-aromatic carbocyclic group containing from 3 to 10 ring members, 
 “heterocycloalkyl” means any mono- or bi-cyclic non-aromatic carbocyclic group having from 3 to 10 ring members, and having from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen, which may include fused, bridged or spiro ring systems; 
 
         wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups so defined and the alkyl, alkenyl, alkynyl, alkoxy groups, may be optionally substituted by from 1 to 4 groups selected from:
 linear or branched (C 1 -C 6 )alkyl, optionally substituted by a group selected from:
 linear or branched (C 1 -C 6 )alkoxy, optionally substituted by linear or branched (C 1 -C 6 )alkoxy, 
 linear or branched (C 1 -C 6 )polyhaloalkyl, 
 hydroxy, 
 halogen, 
 oxo, 
 —NR′R″, 
 —O—C(O)—R′, and 
 —CO—NR′R″; 
 
 linear or branched (C 2 -C 6 )alkenyl; 
 linear or branched (C 2 -C 6 )alkynyl, optionally substituted by linear or branched (C 1 -C 6 )alkoxy; 
 linear or branched (C 1 -C 6 )alkoxy, optionally substituted by a group selected from:
 linear or branched (C 1 -C 6 )alkoxy, 
 linear or branched (C 1 -C 6 )polyhaloalkyl, 
 linear or branched (C 2 -C 6 )alkynyl, 
 —NR′R″, and 
 hydroxy; 
 
 (C 1 -C 6 )alkyl-S—, optionally substituted by linear or branched (C 1 -C 6 )alkoxy; 
 hydroxy; 
 oxo (or N-oxide where appropriate); 
 nitro; 
 cyano; 
 —C(O)—OR′; 
 —O—C(O)—R′; 
 —CO—NR′R″; 
 —NR′R″; 
 —(C═NR′)—OR″; 
 linear or branched (C 1 -C 6 )polyhaloalkyl; 
 trifluoromethoxy; and 
 halogen; 
 
         wherein R′ and R″ independently of one another represent a hydrogen atom or a linear or branched (C 1 -C 6 )alkyl group, optionally substituted by linear or branched (C 1 -C 6 )alkoxy; and wherein one or more of the carbon atoms of the preceding possible substituents, may be deuterated, 
         or an enantiomer, a diastereoisomer, an atropoisomer, or an addition salt thereof with a pharmaceutically acceptable acid or base, wherein the compound of formula (I) is administered alone or in combination with one or more pharmaceutically acceptable excipients. 
       
     
     
         2 . The method according to  claim 1 , wherein at least one of the groups selected from R 1 , R 2 , and R 3  does not represent hydrogen. 
     
     
         3 . The method according to  claim 1 , wherein n is an integer equal to 1. 
     
     
         4 . The method according to  claim 1 , wherein A represents linear or branched (C 1 -C 6 )alkyl or halogen. 
     
     
         5 . The method according to  claim 1 , wherein X represents a carbon atom. 
     
     
         6 . The method according to  claim 1 , wherein R 12  represents hydrogen. 
     
     
         7 . The method according to  claim 1 , wherein: 
       
         
           
           
               
               
           
         
       
       represents 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method according to  claim 1 , wherein: 
       
         
           
           
               
               
           
         
       
       represents 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method according to  claim 1 , wherein R 4  represents optionally substituted linear or branched (C 1 -C 6 )alkoxy or —O-alkyl(C 1 -C 6 )—R 9 . 
     
     
         10 . The method according to  claim 1 , wherein R 5  represents hydrogen. 
     
     
         11 . The method according to  claim 1 , wherein: 
       
         
           
           
               
               
           
         
       
       represents 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method according to  claim 1 , wherein R 6  represents hydrogen, optionally substituted linear or branched (C 1 -C 8 )alkyl, or heteroarylalkyl(C 1 -C 6 ). 
     
     
         13 . The method according to  claim 1 , wherein R 7  represents linear or branched (C 1 -C 6 )alkyl, linear or branched (C 2 -C 6 )alkenyl, linear or branched (C 2 -C 6 )alkynyl, aryl, or heteroaryl. 
     
     
         14 . The method according to  claim 1 , wherein R 8  and R 8 ′ independently of one another represent linear or branched (C 1 -C 6 )alkyl, or (R 8 , R 8 ′), together with the nitrogen atom carrying them, form a non-aromatic ring having from 5 to 7 ring members, which ring may have, in addition to the nitrogen atom, from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen, wherein the nitrogen in question may be substituted by hydrogen atom or linear or branched (C 1 -C 6 )alkyl. 
     
     
         15 . The method according to  claim 1 , wherein R 9  represents -Cy 1 , -Cy 1 -alkyl(C 0 -C 6 )-Cy 2 , or -Cy 1 -alkyl(C 0 -C 6 )—O-alkyl(C 0 -C 6 )-Cy 2 . 
     
     
         16 . The method according to  claim 15 , wherein Cy 1  represents heteroaryl. 
     
     
         17 . The method according to  claim 15 , wherein Cy 2  represents phenyl, pyridinyl, pyrazolyl, morpholinyl, furanyl, or cyclopropyl. 
     
     
         18 . The method according to  claim 15 , wherein R 9  represents -Cy 1 -Cy 2  wherein Cy 1  represents pyrimidinyl and Cy 2  represents phenyl, pyridinyl, pyrazolyl, morpholinyl, furanyl, or cyclopropyl. 
     
     
         19 . The method according to  claim 1 , wherein the compound of formula (I) is selected from:
 (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(furan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-methoxyphenyl) propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(furan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-(2-methoxyethoxy) phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-(2,2,2-trifluoroethoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-(pyrazin-2-yl methoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(1-methyl-1H-pyrazol-5-yl)methoxy]phenyl}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(propan-2-yl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(propan-2-yl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(trifluoromethyl) pyridin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-ethoxy pyrimidin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(propan-2-yloxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(pyridin-2-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy ethyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(furan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(cyclopropyl methoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-3-{2-[(1-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-3-{2-[(1-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-3-{2-[(1-tert-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   ethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(propan-2-yl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoate,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-cyclopropylpyrimidin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(furan-2-yl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-propyl pyrimidin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(thiophen-2-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(morpholin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(pyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-ethoxy pyrimidin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy ethoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyethyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(1H-pyrazol-1-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-methoxy pyridin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-3-{2-[(1-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methyl pyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-3-{2-[(1-butyl-1H-1,2,3-triazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(4-methyl pyridin-3-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(morpholin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-({2-[(2-methoxy ethyl)amino]pyrimidin-4-yl}methoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methyl phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(morpholin-4-yl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(morpholin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-ethoxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3-methyl pyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3,3,3-trifluoropropoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3-methyl pyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(methoxy methyl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3-methylpyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2(4-methylpyridin-3-yl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   ethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]methoxy}phenyl)propanoate,   ethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   2,2,2-trifluoroethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   propan-2-yl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl) ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   2-methoxyethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   ethyl (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy}phenyl)propanoate,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(pyridin-3-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(ethoxy methyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-3-{2-[(1-tert-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-fluoro phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-{2-[(2-methoxy pyrimidin-4-yl)methoxy]phenyl}propanoic acid,   (2R)-3-124(1-tert-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-hydroxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-({2-[2-(propan-2-yloxy)phenyl]pyrimidin-4-yl}methoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-({2-[2-(2-methoxyethoxy)phenyl]pyrimidin-4-yl}methoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-ethyl phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-[2-({2-[4-methoxy-2-(trifluoromethyl)phenyl]pyrimidin-4-yl}methoxy)phenyl]propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2,5-dimethylpyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(5-methoxy-2-methylpyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-ethyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{2-bromo-3-chloro-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{2,3-dichloro-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-3-{2-[(1-tert-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-fluorophenyl) pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-[(6-[4-(benzyloxy)phenyl]-(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methyl piperazin-1-yl)ethoxy]phenyl}thieno[2,3-d]pyrimidin-4-yl)oxy]-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-[((5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-[4-(pyridin-4-ylmethoxy)phenyl]thieno[2,3-d]pyrimidin-4-yl)oxy]-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-phenylbut-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   methyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl) ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   ethyl (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(4-ethylpiperazin-1-yl)ethoxy]-2-methyl phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-fluoro phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate,   ethyl (2R)-3-{2-[(1-tert-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-1 [5(5S a )-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl) thieno[2,3-d]pyrimidin-4-yl]oxy}propanoate,   {[(2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxy phenyl)pyrimidin-4-yl]methoxy}phenyl)propanoyl]oxy}methyl 2,2-dimethyl propanoate,   (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl) propanoate,   2-(dimethylamino)-2-oxoethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate, and   2-(2-methoxyethoxy)ethyl (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methyl piperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl}oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoate.   
     
     
         20 . The method according to  claim 1 , wherein the compound of formula (I) is selected from:
 (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3,3,3-trifluoropropoxy)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl}oxy}-3-(2-{[1-(propan-2-yl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl}oxy}-3-(2-{[2-(trifluoromethyl)pyridin-4-yl]methoxy}phenyl) propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(propan-2-yl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoate,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl}oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-3-{2-[(1-butyl-1H-pyrazol-5-yl)methoxy]phenyl}-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(4-methylpyridin-3-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3-methylpyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(prop-1-yn-1-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(3-methylpyridin-4-yl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-4-[2-(dimethylamino)ethoxy]-2-methylphenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{3-chloro-2-ethyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid,   (2R)-2-{[(5S a )-5-{2-bromo-3-chloro-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid, and   (2R)-2-{[(5S a )-5-{2,3-dichloro-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid.   
     
     
         21 . The method according to  claim 1 , wherein the condition is selected from cancer of the bladder, cancer of the uterus, cancer of the colon, cancer of the esophagus, cancer of the liver, ovarian cancer, prostate cancer, and pancreatic cancer. 
     
     
         22 . The method according to  claim 1 , wherein the condition is selected from auto-immune diseases and diseases of the immune system. 
     
     
         23 . The method according to  claim 21 , wherein the compound of formula (I) is administered in combination with an anti-cancer agent selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, kinase inhibitors, and antibodies. 
     
     
         24 . The method according to  claim 21 , wherein the compound of formula (I) is administered in combination with radiotherapy.