Novel tetrahydropyridothiophenes

Abstract

Compounds of a certain formula (I), in which Ra and Rb have the meanings indicated in the description, are novel effective compounds with anti-proliferative and apoptosis inducing activity.

1 - 21 . (canceled) 
   
   
       22 . 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 of formula I 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is 1-4C-alkyl, or 1-4C-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, 
 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, 
 each R2 is the same or different and is independently selected from the group consisting of:
 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 and 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 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 is 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 is 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 is the same or different and is each independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R10 is the same or different 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 optionally 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 Rba, Rbb, Rbc, Rca, Rcb, Rda, Rdb, Rea and Reb is 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 optionally 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 made up of 
 a first constituent being a 5- or 6-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 as defined herein afore, or a heterocyclic ring B as defined herein below, 
 wherein said Har ring or ring system is attached to the parent molecular group via a substitutable ring carbon or ring nitrogen atom, 
 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 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 as defined herein afore, 
 wherein said Het ring or ring system is attached to the parent molecular group via a substitutable ring carbon or ring nitrogen atom; 
 
     under the proviso, that 
     6-acetyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-propionamide 
     is disclaimed; 
     or a salt thereof. 
   
   
       23 . The method according to  claim 22 , wherein the disease or disorder is cancer, or a malignant or benign neoplasia. 
   
   
       24 . The method according to  claim 22 , wherein the disease or disorder is benign hypoplasia, benign hypoplasia of the prostate (“BPH”) or colon epithelium, psoriasias, 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, Retinomblastoma, 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. 
   
   
       25 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib, Ic, Id and Id′ 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is 1-4C-alkyl, or 1-C-alkyl substituted by one or two substituents independently selected from R2, 
 Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is phenyl, 
 
     or
 Q is optionally substituted by Rca and/or Rcb, and is Har, or 
 Q is attached via a carbon atom of the benzene ring to the parent molecular group, and is 1,3-benzodioxolyl, 2,2-difluoro-1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydrobenzofuranyl, chromenyl or chromanyl, 
 
     or
 Q is attached via a carbon atom of the benzene ring to the parent molecular group, and is benzofuranyl, 
 
     or
 Q is tetrahyrofuranyl, 
 
     or
 Q is 3-7C-cycloalkyl, 
 each R2 is 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 is the same or different and is each independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R7 is the same or different and is independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 each R10 is the same or different is independently selected from the group consisting of:
 1-4C-alkyl, halogen, trifluoromethyl, cyano, 
 1-4C-alkoxycarbonyl, carboxyl, and 
 hydroxyl, 
 
 each Rba, Rbb, Rbc, Rca and Rcb is 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 at least one heteroatom independently selected from the group consisting of nitrogen, oxygen and sulphur, 
 wherein said Har radical is attached to the parent molecular group via a ring carbon or ring nitrogen atom, or 
 a 6-membered monocyclic heteroaryl radical comprising one or two nitrogen atoms, wherein said Har radical is attached to the parent molecular group via a ring carbon atom, 
 
 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 radical is attached to the parent molecular group via a ring carbon or ring nitrogen atom; 
 
     or a salt thereof. 
   
   
       26 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib, Ic, Id and Id′ 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 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, 
 Q is optionally substituted by Rba and/or Rbb, and is phenyl, 
 
     or
 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 to the parent molecular group, and is 1,3-benzodioxolyl, 2,2-difluoro-1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydrobenzofuranyl, chromenyl or chromanyl, 
 
     or
 Q is attached via a carbon atom of the benzene ring to the parent molecular group, and is benzofuranyl, 
 
     or
 Q is tetrahyrofuranyl, 
 
     or
 Q is 3-7C-cycloalkyl, 
 each R2 is 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, phenyl-1-4C-alkoxy, and (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, 
 wherein said Har is optionally substituted by one or two substituents independently selected from R10, 
 
 each R3, R4, R5 and R6 is 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 to the parent molecular group via a ring carbon atom or a ring nitrogen atom, and is imidazolyl, pyrazolyl or triazolyl, 
 
     or
 Har is bonded to the parent molecular group via a ring carbon atom, and is pyridinyl, pyrazinyl or pyrimidinyl, 
 R10 is 1-4C-alkyl, 
 each Rba and Rbb is the same or different and is each independently selected from the group consisting of:
 1-4C-alkyl, fluorine, chlorine, bromine, trifluoromethyl, cyano, and hydroxyl, 
 
 each Rca and Rcb is the same or different and is each independently selected from the group consisting of:
 1-4C-alkyl, fluorine, chlorine, trifluoromethyl, and cyano; 
 
 
     or a salt thereof. 
   
   
       27 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is 1-4C-alkyl,
 or 
 1-4C-alkyl which is substituted by one substituent selected from R2, 
 or 
 1-2C-alkyl which is substituted by 2,2-dimethyl-[1,3]dioxolan-4-yl, 
 or 
 3-4C-alkyl which is substituted by two hydroxyl radicals on different carbon atoms, 
 
 Q is optionally substituted by Rba and/or Rbb, and is phenyl, 
 
     or
 Q is optionally substituted by Rca and/or Rcb, and is pyridinyl, furanyl, thiophenyl or pyrazol-1-yl, 
 
     or
 Q is 1,3-benzodioxol-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, 
 each R2 is the same or different and is independently selected from the group consisting of:
 pyridyl, pyrimidinyl, R201- and/or R202-substituted pyridyl, R201- and/or R202-substituted pyrimidinyl, morpholino, imidazol-1-yl, pyrazol-1-yl, mono- or di-(R201)-substituted imidazol-1-yl, mono- or di-(R201)-substituted pyrazol-1-yl, 1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazol-1-yl, R201-substituted 1N-(1-4C-alkyl)-imidazolyl, R201-substituted 1N-(1-4C-alkyl)-pyrazol-1-yl, 1N—(H)-imidazolyl, 1N—(H)-pyrazol-1-yl, R201-substituted 1N—(H)-imidazolyl, R201-substituted 1N—(H)-pyrazol-1-yl, 
 —C(O)OR4, —OC(O)R3, 
 —OR4, 
 phenyl-1-2C-alkoxy, 
 1-2C-alkoxy-2-3C-alkoxy, and 
 (1-2C-alkoxy-2-3C-alkoxy)-2-3C-alkoxy, 
 
 R3 is 1-4C-alkyl, 
 each R4 is the same or different and is independently selected from the group consisting of:
 hydrogen, and 1-4C-alkyl, 
 
 R201 is 1-4C-alkyl, 
 R202 is 1-4C-alkyl, 
 each Rba and Rbb is the same or different and is each independently selected from the group consisting of:
 methyl, ethyl, fluorine, chlorine, bromine, and trifluoromethyl, 
 
 each Rca and Rcb is the same or different and is each independently selected from the group consisting of:
 methyl, ethyl, fluorine, chlorine, and trifluoromethyl; 
 
 
     or a salt thereof. 
   
   
       28 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, in which 
 R1 is methyl, ethyl or propyl, 
 
     or
 R1 is (R2)-methyl, 2-(R2)-ethyl, or 3-(R2)-propyl, 
 
     or
 R1 is 2,3-dihydroxypropyl, 
 Q is unsubstituted, and is phenyl, 
 
     or
 Q is unsubstituted, and is pyridinyl, furanyl or thiophenyl, 
 
     or
 Q is substituted by Rba and/or Rbb, and is phenyl, 
 
     or
 Q is substituted by Rca and/or Rcb, and is pyridinyl, furanyl or thiophenyl, 
 
     or
 Q is cyclohexyl or cyclopentyl, 
 each R2 is the same or different and is independently selected from the group consisting of:
 pyridyl, pyrimidinyl, methyl-substituted pyridyl, imidazol-1-yl, mono- or di-methyl-substituted imidazol-1-yl, 1N-methyl-imidazolyl, carboxyl, methoxycarbonyl, hydroxyl, methylcarbonyloxy, methoxy, ethoxy, benzyloxy, and 2-methoxyethoxy, 
 
 each Rba and Rbb is the same or different and is each independently selected from the group consisting of:
 methyl, ethyl, fluorine and chlorine, 
 
 each Rca and Rcb is the same or different and is each independently selected from the group consisting of:
 methyl, ethyl and chlorine; 
 
 
     or a salt thereof. 
   
   
       29 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is pyridyl, 
 
     or
 R1 is (R2)-methyl, in which 
 R2 is 1N-methyl-imidazolyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is hydroxyl or methoxy, 
 
     or
 R1 is (2-methoxyethoxy)-methyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is imidazol-1-yl, or mono- or di-methyl-substituted imidazol-1-yl; 
 Q is unsubstituted, and is pyridinyl, 
 
     or
 Q is unsubstituted, and is furanyl, 
 
     or
 Q is unsubstituted, and is thiophenyl, 
 or 
 Q is 2-(Rba)-phenyl, in which 
 Rba is methyl, ethyl, chlorine or fluorine, 
 
     or
 Q is 3-(Rba)-phenyl, in which 
 Rba is methyl, ethyl, chlorine or fluorine, 
 
     or
 Q is 5-(Rca)-furan-2-yl, in which 
 Rca is methyl or chlorine, 
 
     or
 Q 5-(Rca)-4-(Rcb)-furan-2-yl, in which 
 Rca is methyl or chlorine, 
 Rcb is methyl, 
 
     or
 Q is 5-(Rca)-thiophen-2-yl, in which 
 Rca is methyl or chlorine, 
 
     or
 Q is cyclohexyl or cyclopentyl; 
 
     or a salt thereof. 
   
   
       30 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl, 
 
     or
 R1 is (R2)-methyl, in which 
 R2 is 1-methyl-imidazol-2-yl or 1-methyl-imidazol-5-yl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is hydroxyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is imidazol-1-yl, 2-methyl-imidazol-1-yl, 4-methyl-imidazol-1-yl or 2,4-dimethyl-imidazol-1-yl; 
 Q is unsubstituted, and is phenyl, 
 
     or
 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, 
 
     or
 Q is 2-(Rba)-phenyl, in which 
 Rba is methyl, chlorine or fluorine, 
 
     or
 Q is 3-(Rba)-phenyl, in which 
 Rba is methyl, chlorine or fluorine, 
 
     or
 Q is cyclohexyl; 
 
     or a salt thereof. 
   
   
       31 . The method according to  claim 22 , wherein the compound is one of the formulae Ia, Ib and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is hydroxyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is imidazol-1-yl; 
 Q is unsubstituted, and is phenyl, 
 
     or
 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 cyclohexyl; 
 
     or a salt thereof. 
   
   
       32 . The method according to  claim 22 , wherein the compound is one of the formulae Ia and Ic 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is pyridyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is methoxy, 
 
     or
 R1 is (2-methoxyethoxy)-methyl, 
 
     or
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is imidazol-1-yl; 
 Q is unsubstituted, and is pyridinyl, 
 
     or
 Q is unsubstituted, and is furanyl, 
 
     or
 Q is unsubstituted, and is thiophenyl, 
 
     or
 Q is 2-(Rba)-phenyl, in which 
 Rba is methyl, ethyl, chlorine or fluorine, 
 
     or
 Q is 3-(Rba)-phenyl, in which 
 Rba is methyl, ethyl, chlorine or fluorine, 
 
     or
 Q is 5-(Rca)-furan-2-yl, in which 
 Rca is methyl or chlorine, 
 
     or
 Q 5-(Rca)-4-(Rcb)-furan-2-yl, in which 
 Rca is methyl or chlorine, 
 Rcb is methyl, 
 
     or
 Q is 5-(Rca)-thiophen-2-yl, in which 
 Rca is methyl or chlorine; 
 
     or a salt thereof. 
   
   
       33 . The method according to  claim 22 , wherein the compound is one of the formulae Ia and 
     
       
         
         
             
             
         
       
     
     wherein
 Ra is —C(O)R1, 
 R1 is (R2)-methyl, or 2-(R2)-ethyl, in which 
 R2 is pyridyl, 
 
     or
 R1 is 2-(R2)-ethyl, in which 
 R2 is imidazol-1-yl; 
 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, 
 
     or
 Q is 2-(Rba)-phenyl, in which 
 Rba is methyl, chlorine or fluorine, 
 
     or
 Q is 3-(Rba)-phenyl, in which 
 Rba is methyl, chlorine or fluorine; 
 
     or a salt thereof. 
   
   
       34 . 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 selected from the group consisting of 
     N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     4-[3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyric acid methyl ester, 
     Acetic acid 2-[3-cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxo-ethyl ester, 
     N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-{3-Cyano-6-[3-(4-methyl-piperazin-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     N-[3-Cyano-6-(3-morpholin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     N-{3-Cyano-6-[3-(2-methyl-benzoimidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-butyramide, 
     N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-propionamide, 
     (RS)—N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     (RS)—N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     (RS)—N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     (RS)—N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-butyramide, 
     N-{3-Cyano-6-[3-(2,4-dimethyl-imidazo-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-propionamide, 
     N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-propionamide, 
     (RS)—N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     (RS)—N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-butyramide, 
     N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-cyclohexyl-propionamide, 
     N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-propionamide, 
     N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-propionamide, 
     N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-propionamide, 
     N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-2-yl-propionamide, 
     N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-2-yl-propionamide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid {3-cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-amide, 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, and 
     (1RS,2RS)-2-Phenyl-cyclopropanecarboxylic acid [3-cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, 
     and salts thereof. 
   
   
       35 . The method according to  claim 34 , 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, Retinomblastoma, 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. 
   
   
       36 . The method according to  claim 22 , wherein an enantiomer of a compound according to claim  1  or a salt thereof is administed. 
   
   
       37 . The method according to  claim 22 , further comprising administering at least one further anti-cancer agent selected from the group consisting of chemotherapeutic anti-cancer agents and target-specific anti-cancer agents,
 for separate, sequential, simultaneous, concurrent or chronologically staggered use in therapy.   
   
   
       38 . The method according to  claim 22 , wherein said chemotherapeutic anti-cancer agents are selected from the group consisting of (i) alkylating/carbamylating agents; (ii) platinum derivatives; (iii) antimitotic agents/tubulin inhibitors; (iv) topoisomerase inhibitors; (v) pyrimidine antagonists; (vi) purin antagonists; and (vii) folic acid antagonists. 
   
   
       39 . The method according to  claim 22 , wherein said target-specific anti-cancer agents are selected from the group consisting of (i) kinase inhibitors; (ii) proteasome inhibitors; (iii) histone deacetylase inhibitors; (iv) heat shock protein 90 inhibitors; (v) vascular targeting agents, anti-angiogenic drugs, and KDR tyrosine kinase inhibitors; (vi) monoclonal antibodies, mutants and conjugates of monoclonal antibodies, and antibody fragments; (vii) oligonucleotide based therapeutics; (viii) Toll-like receptor/TLR 7 agonists, TLR 7 agonists and TLR 7/8 agonists; (ix) protease inhibitors; (x) hormonal therapeutics; (xi) aromatase inhibitors; (xii) bleomycin; (xiii) retinoids; (xiv) DNA methyltransferase inhibitors; (xv) alanosine; (xvi) cytokines; (xvii) interferons; (xviii) death receptor agonists; (xix) DR4/5 agonistic antibodies; (xx) FasL; and (xxi) TNF-R agonists.