Tetrahydropyridothiophenes for the treatment of proliferative diseases such as cancer

Abstract

The invention relates to compounds of formula I, wherein Ra is —C(O)OR1, in which R1 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by one to four substituents independently selected from R2, Rb is -T-Q, in which T is 1-6C-alkylene or 3-7C-cycloalkylene, and either Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is phenyl or naphthyl, or Q is optionally substituted by Rca and/or Rcb, and is Har, or Q is optionally substituted by Rda and/or Rdb, and is Het, or Q is optionally substituted by Rea and/or Reb, and is 3-7C-cycloalkyl, which are useful for the therapy of hyperproliferative diseases, in particular human cancer.

1 - 20 . (canceled) 
     
     
         21 . A compound of formula I 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by one to four substituents independently selected from R2, 
 Rb is -T-Q, 
 T is 1-6C-alkylene or 3-7C-cycloalkylene, 
 Q is optionally substituted by Rca and/or Rcb, and is Har, 
 
       or
 Q is optionally substituted by Rda and/or Rdb, and is Het, 
 
       or
 Q is optionally substituted by Rea and/or Reb, and is 3-7C-cycloalkyl, 
 each R2 may be the same or different and is independently selected from the group consisting of:
 1-4C-alkyl, 3-7C-cycloalkyl, phenyl, Har, Het, halogen, trifluoromethyl, nitro, cyano, —C(O)R3, —C(O)OR4, —C(O)N(R5)R6, —S(O) 2 R3, —S(O) 2 N(R5)R6, —N(R7)C(O)R3, —N(R7)C(O)OR4, —N(R7)C(O)N(R5)R6, guanidino, —OC(O)R3, completely or predominantly fluorine-substituted 1-4C-alkoxy, —O[C(R8)R9] y N(R5)R6, —O[C(R8)R9] y C(O)N(R5)R6, 
 —OR4, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, pyridyl-1-4C-alkoxy, (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, —N(R5)R6, and —SR3, wherein each of said 1-4C-alkyl, 3-7C-cycloalkyl, phenyl, Har and Het is optionally substituted by one to four substituents independently selected from R10, 
 
 each R3, R4, R5 and R6 may be the same or different and is each independently selected from the group consisting of:
 hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, phenyl, and phenyl-1-4C-alkyl, 
 
 each R7 may be the same or different and is independently selected from the group consisting of:
 hydrogen, 1-7C-alkyl, and 3-7C-cycloalkyl, 
 
 each R8 and R9 may be the same or different and is each independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R10 may be the same or different and is independently selected from the group consisting of:
 1-4C-alkyl, phenyl, halogen, trifluoromethyl, cyano, 1-4C-alkoxycarbonyl, carboxyl, hydroxyl, and phenoxy, 
 wherein each of said phenyl and phenoxy radicals can be unsubstituted or substituted by up to four halogen radicals and up to two 1-4C-alkyl, hydroxyl, trifluoromethyl or cyano radicals, 
 
 each y is 1, 2, 3 or 4, 
 each Rca, Rcb, Rda, Rdb, Rea and Reb may be the same or different and is each independently selected from the group consisting of:
 1-4C-alkyl, phenyl, halogen, trifluoromethyl, cyano, 1-4C-alkoxycarbonyl, carboxyl, hydroxyl, and phenoxy, 
 wherein each of said phenyl and phenoxy can be unsubstituted or substituted by up to four halogen radicals and up to two 1-4C-alkyl, hydroxyl, trifluoromethyl or cyano radicals, 
 
 each Har is the same or different and is independently a fully aromatic or partially aromatic mono- or fused bicyclic ring or ring system, which contains at least one heteroatom in the ring membered monocyclic unsaturated, aromatic heteroaryl ring A,
 which heteroaryl ring A comprises at least one heteroatom independently selected from the group consisting of nitrogen, oxygen and sulfur, 
 
 and, optionally, fused to said first constituent, 
 a second constituent being a benzene ring, a 5-6C-cycloalkane ring, an additional heteroaryl ring A or a heterocyclic ring B, 
 wherein said Har is attached via a substitutable ring carbon or ring nitrogen atom of Har, 
 each Het is the same or different and is independently a fully saturated or partially unsaturated mono- or fused bicyclic ring or ring system made up of a first constituent being a 3- to 7-membered monocyclic fully saturated or partially unsaturated, non-aromatic heterocyclic ring B,
 which heterocyclic ring B comprises one to three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, 
 and which heterocyclic ring B is optionally substituted by one or two oxo groups, 
 
 and, optionally, fused to said first constituent, 
 a second constituent being a benzene ring, a 3-7C-cycloalkane ring, or an additional heterocyclic ring B, 
 wherein said Het is attached via a substitutable ring carbon or ring nitrogen atom; 
 under the first proviso, that those compounds, in which T is methylene substituted by 1-5C-alkyl, are disclaimed, and 
 under the second proviso, that 
 3-cyano-2-(2-morpholin-4-yl-ethanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester , 
 3-cyano-2-(2-indolin-1-yl-ethanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester and 
 3-cyano-2-(3-phenyl-propanyolamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester are also disclaimed; 
 or a salt thereof. 
 
     
     
         22 . The compound according to  claim 21 , which is of formula Ia, Ib, Ic, Id or Id′ 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is 1-4C-alkyl, or 1-7C-alkyl substituted by one or two substituents independently selected from R2, 
 Q is optionally substituted by Rca and/or Rcd, and is Har, 
 
       or
 Q is attached via a carbon atom of the benzene ring, and is 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, chromenyl, chromanyl, 2,2-difluoro-1,3-benzodioxolyl, or 2,3-dihydrobenzofuranyl, 
 
       or
 Q is attached via a carbon atom of the benzene ring, and is benzofuranyl, 
 
       or
 Q is tetrahydrofuranyl, 
 
       or
 Q is 3-7C-cycloalkyl, 
 
       wherein
 each R2 may be the same or different and is independently selected from the group consisting of:
 Har, Het, —C(O)R3, —C(O)OR4, —C(O)N(R5)R6, —N(R7)C(O)R3, —OC(O)R3, —OR4, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, pyridyl-1-4C-alkoxy, (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, and phenyl-1-4C-alkoxy, 
 wherein each of said Har and Het is optionally substituted by one or two substituents independently selected from R10, 
 
 each R3, R4, R5 and R6 may be the same or different and is each independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R7 may be the same or different and is independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R10 may be the same or different and is independently selected from the group consisting of:
 1-4C-alkyl, halogen, trifluoromethyl, cyano, 1-4C-alkoxycarbonyl, carboxyl, and hydroxyl, 
 
 each Rca and Rcb may be the same or different and is each independently selected from the group consisting of:
 1-4C-alkyl, halogen, trifluoromethyl, cyano, 1-4C-alkoxycarbonyl, carboxyl, and hydroxyl, 
 
 each Har is the same or different and is independently
 a 5-membered monocyclic heteroaryl radical comprising one to four heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulphur, wherein said Har is attached via a ring carbon or ring nitrogen atom of Har, 
 
 or
 a 6-membered monocyclic heteroaryl radical comprising one or two nitrogen atoms, wherein said Har is attached via a ring carbon atom of Har, 
 
 Het is a 3- to 7-membered monocyclic fully saturated heterocyclic ring comprising one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulphur,
 wherein said Het is attached via a ring carbon or ring nitrogen atom. 
 
 
     
     
         23 . The compound according to  claim 21 , which is of formula Ia, Ib, Ic, Id or Id′ 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is 1-4C-alkyl, 1-4C-alkyl substituted by one substituent selected from R2, or 3-4C-alkyl substituted by two hydroxyl radicals on different carbon atoms, and 
 Q is optionally substituted by Rca and/or Rcb, and is pyridinyl, furanyl, thiophenyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl or imidazolyl, 
 
       or
 Q is attached via a carbon atom of the benzene ring, and is 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, chromenyl, chrornanyl, 2,2-difluoro-1,3-benzodioxolyl or 2,3-dihydrobenzofuranyl, 
 
       or
 Q is attached via a carbon atom of the benzene ring, and is benzofuranyl, 
 
       or
 Q is tetrahydrofuranyl, 
 
       or
 Q is 3-7C-cycloalkyl, 
 each R2 may be the same or different and is independently selected from the group consisting of:
 Har, morpholino, 4-methyl-piperazin-1-yl, —C(O)R3, —C(O)OR4, —C(O)N(R5)R6, —N(R7)C(O)R3, 
 —OC(O)R3, —OR4, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, pyridyl-1-4C-alkoxy, (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, and phenyl-1-4C-alkoxy, 
 wherein each of said Har and Het is optionally substituted by one or two substituents independently selected from R10, 
 
 each R3, R4, R5 and R6 may be the same or different and is each independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 R7 is hydrogen, 
 Har is bonded via a ring carbon atom or a ring nitrogen atom of Har, and is imidazolyl, pyrazolyl or triazolyl, 
 
       or
 Har is bonded via a ring carbon atom of Har, and is pyridinyl, pyrazinyl or pyrimidinyl, 
 R10 is 1-4C-alkyl, 
 each Rca and Rcb may be the same or different and is each independently selected from the group consisting of:
 1-4C-alkyl, fluorine, chlorine, trifluoromethyl, and cyano. 
 
 
     
     
         24 . The compound according to  claim 21 , which is of formula Ia, Da or Ic 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is 1-4C-alkyl, 
 
       or
 R1 is 1-4C-alkyl which is substituted by R2, 
 R2 is pyridyl, pyrimidinyl, R201- and/or R202-substituted pyridyl, or R201- and/or R202-substituted pyrimidinyl, 
 
       or
 R1 is 1-4C-alkyl which is substituted by R2, 
 R2 is 1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl, R201-substituted 1N-(1-4C-alkyl)-imidazolyl, or R201-substituted 1N-(1-4C-alkyl)-pyrazolyl, 
 
       or
 R1 is 1-4C-alkyl which is substituted by R2, 
 R2 is 1N—(H)-imidazolyl, 1N—(H)-pyrazolyl, R201-substituted 1N—(H)-imidazolyl, or R201-substituted 1N—(H)-pyrazolyl, 
 
       or
 R1 is 3-4C-alkyl which is substituted by two hydroxyl radicals on different carbon atoms, 
 
       or
 R1 is 1-2C-alkyl which is substituted by 2,2-dimethyl-[1,3]-dioxolan-4-yl, 
 
       or
 R1 is 1-4C-alkyl which is substituted by R2, 
 R2 is —C(O)OR4, 
 
       or
 R1 is 2-4C-alkyl which is substituted by R2, 
 R2 is morpholine, —OC(O)R3, —OR4, phenyl-1-2C-alkoxy, 1-2C-alkoxy-2-3C-alkoxy, or (1-2C-alkoxy-2-3C-alkoxy)-2-3C-alkoxy, 
 
       or
 R1 is 2-4C-alkyl which is substituted by R2, 
 R2 is imidazol-1-yl, pyrazol-1-yl, mono- or di-(R201)-substituted imidazol-1-yl, or mono- or di-(R201)-substituted pyrazol-1-yl, 
 Q is optionally substituted by Rca and/or Rcb, and is pyridinyl, furanyl, thiophenyl or pyrazol-1-yl, 
 
       or
 Q is 1,3-benzodioxo1-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl, 2,2-difluoro-1,3-benzodioxol-5-yl, chromen-6-yl, chromen-7-yl, chroman-6-yl, chroman-7-yl, 2,3-dihydrobenzofuran-5-yl, or 2,3-dihydrobenzofuran-6-yl, 
 
       or
 Q is benzofuran-5-yl, or benzofuran-6-yl, 
 
       or
 Q is tetrahydrofuranyl, 
 
       or
 Q is 5-6C-cycloalkyl, 
 R201 is 1-4C-alkyl, 
 R202 is 1-4C-alkyl, 
 each Rca and Rcb may be the same or different and is each independently selected from the group consisting of: methyl, ethyl, fluorine, chlorine, and trifluoromethyl. 
 
     
     
         25 . The compound according to  claim 21 , which is of formula Ia, Ib or Ic 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is methyl, ethyl or propyl, 
 
       or
 R1 is (R2)-methyl, 2-(R2)-ethyl, or 3-(R2)-propyl, 
 R2 is pyridyl, pyrimidinyl, or methyl-substituted pyridyl, 
 
       or
 R1 is (R2)-methyl, 2-(R2)-ethyl, or 3-(R2)-propyl, 
 R2 is 1N-methyl-imidazolyl, 
 
       or
 R1 is 2,3-dihydroxy-propyl, 
 
       or
 R1 is (R2)-methyl, 2-(R2)-ethyl, or 3-(R2)-propyl, 
 R2 is carboxyl or methoxycarbonyl, 
 
       or
 R1 is 2-(R2)-ethyl, or 3-(R2)-propyl, 
 R2 is hydroxyl, methylcarbonyloxy, methoxy, ethoxy, benzyloxy, or 2-methoxyethoxy, 
 
       or
 R1 is 2-(R2)-ethyl, or 3-(R2)-propyl, 
 R2 is imidazol-1-yl, or mono- or di-methyl-substituted imidazol-1-yl; 
 
       and wherein
 Q is unsubstituted, and is pyridinyl, furanyl or thiophenyl, 
 
       or
 Q is substituted by Rca and/or Rcb, and is pyridinyl, furanyl or thiophenyl, 
 
       in which
 each Rca and Rcb may be the same or different and is each independently selected from the group consisting of:
 methyl, ethyl and chlorine. 
 
 
     
     
         26 . The compound according to  claim 21 , which is of formula Ia or Ic 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, 
 R2 is pyridyl, 
 
       or
 R1 is 2,3-dihydroxy-propyl, 
 
       or
 R1 is 2-(R2)-ethyl, 
 R2 is hydroxyl or methoxy, 
 
       or
 R1 is 2-(R2)-ethyl, 
 R2 is imidazol-1-yl; 
 
       and wherein
 Q is unsubstituted, and is pyridinyl, 
 
       or
 Q is unsubstituted, and is furanyl, 
 
       or
 Q is unsubstituted, and is thiophenyl, 
 
       or
 Q is 5-(Rca)-furan-2-yl, in which Rca is methyl or chlorine, 
 
       or
 Q is 5-(Rca)-4-(Rcb)-furan-2-yl, in which 
 Rea is methyl or chlorine, 
 Rcb is methyl, 
 
       or
 Q is 5-(Rca)-thiophen-2-yl, in which 
 Rca is methyl or chlorine. 
 
     
     
         27 . The compound according to  claim 21 , which is of formula Ia or Ic 
       
         
           
           
               
               
           
         
       
       wherein
 Ra is —C(O)OR1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, 
 R2 is pyridyl, 
 
       or
 R1 is 2,3-dihydroxy-propyl, 
 
       or
 R1 is 2-(R2)-ethyl, 
 R2 is hydroxyl, 
 
       or
 R1 is 2-(R2)-ethyl, 
 R2 is imidazol-1-yl; 
 
       and wherein
 Q is unsubstituted, and is pyridin-2-yl, 
 
       or
 Q is unsubstituted, and is pyridin-3-yl, 
 
       or
 Q is unsubstituted, and is furan-2-yl, 
 
       or
 Q is unsubstituted, and is thiophen-2-yl. 
 
     
     
         28 . The compound according to  claim 21 , which is of formula Ia or Ic 
       
         
           
           
               
               
           
         
       
       wherein
 Q is selected from the group consisting of furan-2-yl, thiophen-2-yl, pyridin-2-yl and pyridin-3-yl. 
 
     
     
         29 . A compound selected from the group consisting of
 3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-thiophen-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-[3-(4,5-dimethyl-furan-2-yl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester,   3-Cyano-2-(3-cyclohexyl-propanoylamino)-4,7-dihydro-5H-1-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-[3-(5-methyl-pyrazol-1-yl)-propanoylamino]-4,7-dihydro -5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-tetrahydro-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   2-(3-Benzo[1,3]dioxol-4-yl-propanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-[3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-2,3-dihydro -benzo[1,4]dioxin-5-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-pyrimidin-5-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-e]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,   3-Cyano-2-{[1-(2-furan-2-yl-cyclopropyl)-methanoyl]-amino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-morpholin-4-yl-ethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-morpholin-4-yl-ethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester,   3-Cyano-2-(3-furan-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyri din-3-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro -5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 1-methyl-1H-imidazol-2-ylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methyl-3H-imidazol-4-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-24(RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2,4-dimethyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid carboxymethyl ester,   3-Cyano-24(RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-1-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,   3-Cyano-24(R,S)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyri dine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester,   3-Cyano-24(RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 1-methyl-1H-imidazol-2-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methyl-3H-imidazol-4-ylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2,4-dimethyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid carboxymethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyri dine-6-carboxylic acid 2-hydroxy-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,   3-Cyano-2-(3-pyri din-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 1-methyl-1H-imidazol-2-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methyl-3H-imidazol-4-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2,4-dimethyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-e]pyridine-6-carboxylic acid carboxymethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro -5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 1-methyl-1H-imidazol-2-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methyl-3H-imidazol-4-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2,4-dimethyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-e]pyridine-6-carboxylic acid 2-(4-methyl-imidazol-1-yl)-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-e]pyridine-6-carboxylic acid carboxymethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methoxycarbonylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyri dine-6-carboxylic acid methoxycarbonylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methoxycarbonylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methoxycarbonylmethyl ester,   3-Cyano-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[4,3]dioxolan-4-ylmethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester,   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester,   3-Cyano-24(RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyri dine-6-carboxylic acid 2-acetoxy-ethyl ester,   3-Cyano-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester,   3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-1-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester, and   3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-1-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester,   and salts thereof.   
     
     
         30 . The compound according to  claim 21 , which is of formula Ic* 
       
         
           
           
               
               
           
         
       
     
     
         31 . The compound according to  claim 21 , which is of formula Ic** 
       
         
           
           
               
               
           
         
       
     
     
         32 . The compound according to  claim 21 , wherein T is 3-6C-alkylene or 3-7C-cycloalkylene. 
     
     
         33 . A pharmaceutical composition comprising one or more compounds according to  claim 21 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient, diluent and/or carrier. 
     
     
         34 . A pharmaceutical composition comprising one or more compounds according to  claim 29 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient, diluent and/or carrier. 
     
     
         35 . A method for treating a (hyper)proliferative disease of benign or malignant behaviour and/or disorder responsive to the induction of apoptosis in a patient, comprising administering to said patient in need thereof a therapeutically effective amount of a compound according to  claim 21 . 
     
     
         36 . The method according to  claim 35 , wherein the disease or disorder is cancer, or a malignant or benign neoplasia. 
     
     
         37 . The method according to  claim 35 , wherein the disease or disorder is benign hypoplasia, benign hypoplasia of the prostate (“BPH”) or colon epithelium, psoriasis, glomerulonephritis, osteoarthritis, a malignant neoplasia, a solid or hematological tumor, a tumor of the breast, bladder, bone, brain, central or peripheral nervous system, colon, endocrine glands, thyroid gland, adrenal cortex, esophagus, endometrium, germ cells, head and neck, kidney, liver, lung, larynx, hypopharynx, mesothelioma, sarcoma, ovary, pancreas, prostate, rectum, renal, small intestine, soft tissue, testis, stomach, skin, ureter, vagina or vulva, Retinoblastoma, Wilms tumor, leukemia, lymphoma, non-Hodgkins disease, chronic or acute myeloid leukemia (CML/AML), acute lymphoblastic leukemia (ALL), Hodgkins disease, multiple myeloma, T-cell lymphoma, myelodysplastic syndrome, plasma cell neoplasia, paraneoplastic syndrome, a cancer of unknown primary site or an AIDS related malignancy. 
     
     
         38 . A method for treating a (hyper)proliferative disease of benign or malignant behaviour and/or disorder responsive to the induction of apoptosis in a patient, comprising administering to said patient in need thereof a therapeutically effective amount of a compound according to  claim 29 . 
     
     
         39 . The method according to  claim 38 , wherein the disease or disorder is cancer, or a malignant or benign neoplasia. 
     
     
         40 . The method according to  claim 38 , wherein the disease or disorder is benign hypoplasia, benign hypoplasia of the prostate (“BPH”) or colon epithelium, psoriasis, glomerulonephritis, osteoarthritis, a malignant neoplasia, a solid or hematological tumor, a tumor of the breast, bladder, bone, brain, central or peripheral nervous system, colon, endocrine glands, thyroid gland, adrenal cortex, esophagus, endometrium, germ cells, head and neck, kidney, liver, lung, larynx, hypopharynx, mesothelioma, sarcoma, ovary, pancreas, prostate, rectum, renal, small intestine, soft tissue, testis, stomach, skin, ureter, vagina or vulva, Retinoblastoma, Wilms tumor, leukemia, lymphoma, non-Hodgkins disease, chronic or acute myeloid leukemia (CML/AML), acute lymphoblastic leukemia (ALL), Hodgkins disease, multiple myeloma, T-cell lymphoma, myelodysplastic syndrome, plasma cell neoplasia, paraneoplastic syndrome, a cancer of unknown primary site or an AIDS related malignancy.