US2009227577A1PendingUtilityA1
Tetrahydropyridothiophenes for the treatment of proliferative diseases such as cancer
Est. expiryFeb 9, 2025(expired)· nominal 20-yr term from priority
A61P 35/00A61P 35/02A61P 43/00A61P 31/18A61P 25/00C07D 495/04
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The invention relates to compounds of formula I, wherein Ra is —C(O)ORI, 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 Has, 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.
Claims
exact text as granted — not AI-modified1 - 20 . (canceled)
21 . 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)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 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 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)(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 12, 3 or 4,
each Rba, Rbb, Rbc, 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 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 or a heterocyclic ring B,
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 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 ring or ring system is attached to the parent molecular group 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 method according to claim 21 , wherein the disease or disorder is cancer, or a malignant or benign neoplasia.
23 . The method according to claim 21 , 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.
24 . The method according to claim 21 , wherein the compound of formual I 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 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, 2,3-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 to the parent molecular group, 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 Rba, Rbb, Rbc, 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 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.
25 . The method according to claim 21 , wherein the compound of formual I 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 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, 2,3-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 to the parent molecular group, 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 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 may be 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 may be the same or different and is each independently selected from the group consisting of:
1-4C-alkyl, fluorine, chlorine, trifluoromethyl, and cyano.
26 . The method according to claim 21 , wherein the compound of formual I is of formula Ia, Ib 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 morpholino, —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 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,
R201 is 1-4C-alkyl,
P202 is 1-4C-alkyl,
each Rba and Rbb may be 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 may be the same or different and is each independently selected from the group consisting of: methyl, ethyl, fluorine, chlorine, and trifluoromethyl.
27 . The method according to claim 21 , wherein the compound of formual I 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 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,
in which
each Rba and Rbb may be the same or different and is each independently selected from the group consisting of:
methyl, ethyl, fluorine and chlorine,
each Rca and Rcb may be the same or different and is each independently selected from the group consisting of:
methyl, ethyl and chlorine.
28 . The method according to claim 21 , wherein the compound of formual I 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 2-(Rba)-phenyl,
Rba is methyl, ethyl, chlorine or fluorine,
or
Q is 3-(Rba)-phenyl,
Rba is methyl, ethyl, chlorine or fluorine,
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
Rca is methyl or chlorine,
Rcb is methyl,
or
Q is 5-(Rca)-thiophen-2-yl, in which
Rca is methyl or chlorine.
29 . The method according to claim 21 , wherein the compound of formual I 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,
or
Q is 2-(Rba)-phenyl,
Rba is methyl, chlorine or fluorine,
or
Q is 3-(Rba)-phenyl,
Rba is methyl chlorine or fluorine.
30 . The method according to claim 21 , wherein the compound of formual I is of formula Ia or Ic
wherein
Q is selected from the group consisting of 2-chlorophenyl, 2-methylphenyl, 2-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-fluorophenyl, furan-2-yl, thiophen-2-yl, pyridin-2-yl and pyridin-3-yl.
31 . 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
3-Cyano-2-{[1-(2-phenyl-cyclopropyl)-methanoyl]-amino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-(3-o-tolyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-((RS)-3-phenyl-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 ethyl ester,
3-Cyano-2-(2-methyl-3-phenyl-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-(4-fluoro-phenyl)-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-(2-fluoro-phenyl)-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-(3-fluoro-phenyl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
2-[3-(2-Chloro-phenyl)-propanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-(3-p-tolyl-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,
2-[3-(3-Chloro-phenyl)-propanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
2-[3-(4-Chloro-phenyl)-propanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-(3-m-tolyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-(3-cyclohexyl-propanoylamino)-4,7-dihydro-5H-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,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester,
2-[3-(2-Bromo-phenyl)-propanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-benzyloxy-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,
3-Cyano-2-(3-phenyl-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-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl 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-c]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-(3-methyl-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 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-phenyl-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-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-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-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-2-((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-pyridin-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-2-((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-2-((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-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-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-2-((RS)-3-pyridin-3-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,
3-Cyano-2-((RS)-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]pyridine-6-carboxylic acid 2-pyridin-3-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-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-2-((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]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester,
33-Cyano-2-((RS)-3-phenyl-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-phenyl-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-phenyl-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-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,
3-Cyano-2-((RS)-3-phenyl-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-phenyl-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-phenyl-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-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid carboxymethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-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 pyridin-4-ylmethyl ester,
3-Cyano-2-(3-pyridin-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-c]pyridine-6-carboxylic acid carboxymethyl ester,
3-Cyano-2-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-1-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-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-c]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-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 1-methyl-1H-imidazol-2-ylmethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methyl-3H-imidazol-4-ylmethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester,
3-Cyano-2-(3-phenyl-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-phenyl-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-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid-(4-methyl-imidazol-1-yl)-ethyl ester,
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid carboxymethyl ester,
3-Cyano-2-(3-phenyl-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]pyridine-6-carboxylic acid methoxycarbonylmethyl ester,
3-Cyano-2-((RS)-3-phenyl-butanoylamino)-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-(3-pyridin-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methoxycarbonylmethyl ester,
3-Cyano-2-(3-phenyl-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-2-((RS)-3-pyridin-3-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-2-((RS)-3-phenyl-butanoylamino)-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-2-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dim ethyl-[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-2-((RS)-3-pyridin-2-yl-butanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-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-((RS)-3-phenyl-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-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester,
3-Cyano-2-(3-pyridin-3-yl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester, and
3-Cyano-2-(3-phenyl-propanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetoxy-ethyl ester,
and salts thereof.
32 . The method according to claim 21 , wherein the compound of formual I is of formula IC*
33 . The method according to claim 21 , wherein the compound of formual I is of formula Ic**
34 . The method according to claim 21 , wherein T is 3-6C-alkylene or 3-7C-cycloalkylene.
35 . The method according to claim 21 , wherein
Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is phenyl or naphthyl,
36 . 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)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 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 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 Rba, Rbb, Rbc, Rca, Rob, 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 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 or a heterocyclic ring B,
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 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 ring or ring system is attached to the parent molecular group 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, hydrate or hydrate of a salt thereof.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.