US 7,803,945 B2Granted

Tetrahydropyridothiophenes

Assignee4Sc AG

InventorsKlaus Pekari, Thomas Baer, Bjoern Bartels, Mathias Schmidt, Thomas Beckers

Life of this patent

Estimating the term…

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/or apoptosis inducing activity.

Claims20

Dependent claims

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 or a pharmaceutically acceptable salt thereof

wherein
Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, or —C(O)N(R3)R4;
Rb is Q-2-4C-alkenyl, in which
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;
in which
R1, R2 and R3 are the same or different and are independently selected from the group consisting of:
hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R5;
each R4 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted by at least one substituent independently selected from R5;
R5, Rba, Rbb, Rbc, Rca and Rcb are the same or different and are independently selected from the group consisting of:
1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,
halogen, trifluoromethyl, nitro, cyano, guanidino, amidino,
—C(O)R6, —C(O)OR7, —C(O)N(R8)R9, —S(O)2R6, —S(O)2N(R8)R9,
—N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9, —N(R10)S(O)2R6,
—N(R10)S(O)2N(R8)R9,
—OC(O)R6, —OC(O)N(R8)R9,
—OR7, —N(R8)R9 and —SR7,
wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R11;
R6, R7 and R8 are the same or different and are independently selected from the group consisting of:
hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R12;
each R9 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted by at least one substituent independently selected from R12;
each R10 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl;
R11 is R5;
each R12 is independently selected from R5;
each Ar is independently selected from the group consisting of phenyl and naphthyl;
each Har is the same or different and independently a fully aromatic or partially aromatic mono- or fused bicyclic ring or ring system, which contains at least on heteroatom in the ring or ring system, wherein Har is 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 is attached via a substitutable ring carbon or ring nitrogen atom of Har;
each Het 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,
wherein the 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 benzo group, a 3-7C-cycloalkane group, or an additional heterocyclic ring B,
wherein said Het is attached via a substitutable ring carbon or ring nitrogen atom.

35 more elements

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 compounds 1 to 251 and pharmaceutically acceptable salts thereof.

1. N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
2. N-(6-tert-Butoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
3. N-(6-Heptanoyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
4. N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-phenyl)-acrylamide
5. N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(3-trifluoromethyl-phenyl)-acrylamide
6. N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-2-methyl-3-phenyl-acrylamide
7. N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-pyridyl-acrylamide
8. 3-Cyano-2-((E)-3-thiophen-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
9. 3-Cyano-2-((E)-3-thiophen-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
10. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
11. 3-Cyano-2-((E)-3-furan-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
12. 3-Cyano-2-((E)-3-o-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
13. 2-[(E)-3-(3-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
14. 3-Cyano-2-((E)-3-thiophen-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
15. 3-Cyano-2-[(E)-3-(4-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
16. 3-Cyano-2-((E)-3-m-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
17. 3-Cyano-2-[(E)-3-(2-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
18. 3-Cyano-2-[(E)-3-(4-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
19. 3-Cyano-2-[(E)-3-(3-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
20. 3-Cyano-2-[(E)-3-(2,3-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
21. 3-Cyano-2-[(E)-3-(3-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
22. 2-[(E)-3-(4-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
23. 3-Cyano-2-[(E)-3-(2-trifluoromethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
24. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
25. 3-Cyano-2-[(E)-3-(4-nitro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
26. 3-Cyano-2-[(E)-3-(4-dimethylamino-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
27. 3-Cyano-2-((E)-3-p-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
28. 3-Cyano-2-[(E)-3-(2,4-dichloro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
29. 3-Cyano-2-[(E)-3-(3-nitro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
30. 2-((E)-3-Benzo[1,3]dioxol-5-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
31. 3-Cyano-2-[(E)-3-(2,3,4-trimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
32. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester
33. (E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
34. (E)-N-(6-Acetyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
35. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
36. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
37. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethylamide
38. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethylamide
39. (E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-pyridin-3-yl-acrylamide
40. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid isobutyl ester
41. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-propyl ester
42. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid hexyl ester
43. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid butyl ester
44. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methyl ester
45. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methoxy-phenyl ester
46. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid phenyl ester
47. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid phenethyl ester
48. 2-[(E)-3-(2-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
49. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-pentyl ester
50. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
51. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-(2-dimethylamino-ethyl) ester
52. (E)-N-[3-Cyano-6-(1-imidazol-1-yl-methanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
53. (E)-N-[3-Cyano-6-(1-imidazol-1-yl-methanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
54. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester
55. 3-Cyano-2-((E)-3-furan-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester
56. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid tert-butyl ester
57. 2-[(E)-3-(2-Chloro-3,6-difluoro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
58. 3-Cyano-2-[(E)-3-(2,3-difluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
59. 2-[(E)-3-(4-Chloro-2-fluoro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
60. 3-Cyano-2[(E)-3-(4-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
61. 3-Cyano-2[(E)-3-(3-chloro-2-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
62. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
63. 3-Cyano-2-[(E)-3-(2,6-dichloro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
64. 2-[(E)-3-(3-Chloro-thiophen-2-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
65. 3-Cyano-2-[(E)-3-(2,6-difluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
66. 2-[(E)-3-(2-Bromo-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
67. 2-[(E)-3-(2-Chloro-6-fluoro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
68. 3-Cyano-2-[(E)-3-(2,3,6-trifluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
69. 2-[(E)-3-(2-Acetoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
70. 3-Cyano-2-[(E)-3-(2-fluoro-4-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
71. 2-((E)-3-Benzo[b]thiophen-3-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
72. 2-[(E)-3-(5-Chloro-thiophen-2-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
73. 2-((E)-3-Biphenyl-2-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
74. 3-Cyano-2-[(E)-3-(5-methyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
75. 3-Cyano-2-[(E)-3-(3-methyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
76. 3-Cyano-2-[(E)-3-(5-methyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
77. 3-Cyano-2-[(E)-3-(5-ethyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
78. 2-[(E)-3-(5-Chloro-furan-2-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
79. 3-Cyano-2-[(E)-3-(5-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
80. 3-Cyano-2-[(E)-3-(3-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
81. 3-Cyano-2-[(E)-3-(3-phenoxy-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
82. 3-Cyano-2-[(E)-3-(2-ethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
83. 3-Cyano-2-[(E)-3-(2-cyano-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
84. 2-[(E)-3-Benzofuran-2-yl-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
85. 3-Cyano-2-[(E)-3-(5-phenyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
86. 3-Cyano-2-[(E)-3-(2,3-dimethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
87. 3-Cyano-2-[(E)-3-(2,3-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
88. 3-Cyano-2-[(E)-3-(2-morpholin-4-yl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
89. 3-Cyano-2-[(E)-3-(4-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
90. 2-[(E)-3-(4-Chloro-1-methyl-1H-pyrazol-3-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
91. 3-Cyano-2-[(E)-3-(5-phenyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
92. 3-Cyano-2[(E)-3-(2-morpholin-4-yl-pyridin-3-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
93. 3-Cyano-2[(E)-3-(4-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
94. 3-Cyano-2[(E)-3-(3-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
95. 3-Cyano-2[(E)-3-(2-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
96. 3-Cyano-2[(E)-3-(2-ethoxy-3-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
97. 3-Cyano-2[(E)-3-(1-methyl-1H-pyrrol-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
98. 3-Cyano-2[(E)-3-(2-isopropoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
99. 3-Cyano-2[(E)-3-(2-propoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
100. 3-Cyano-2-((E)-3-pyridin-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
101. 3-Cyano-2-((E)-3-pyridin-4-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
102. 3-Cyano-2-[(E)-3-(2,5-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
103. 3-Cyano-2-((E)-3-1-H-pyrrol-2-yl-allanoylamino)-4,7-dihydrdo-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethylester
104. 3-Cyano-2-[(E)-3-(2-phenoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
105. 3-Cyano-2-{(E)-3-[2-(2-hydroxy-ethoxy)-phenyl]-allanoylamino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
106. 5-Cyano-6-[(E)-3-(2,6-dimethoxy-phenyl)-allanoylamino]-1,3,4,7-tetrahydro-[2]pyrindine-2-carboxylic acid ethyl ester
107. 3-Cyano-2-{(E)-3-[3-(2-hydroxy-ethoxy)-phenyl]-allanoyl-amino}-4,7-dihydro-5H-thieno[2,3-c]-pyridine-6-carboxylic acid ethyl ester
108. 3-Cyano-2-[(E)-3-(2,6-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
109. 2-[(E)-3-(5-Bromo-2-ethoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
110. 2-[(E)-3-(5-Bromo-2-methoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
111. 2-((E)-3-Benzo[1,3]dioxol-4-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
112. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-morpholin-4-yl-ethyl ester
113. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-dimethylamino-ethyl ester
114. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyrrolidin-1-yl-ethyl ester
115. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-dimethylamino-propyl ester
116. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester
117. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-pyridin-4-yl-propyl ester
118. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
119. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-piperidin-1-yl-propyl ester
120. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-morpholin-4-yl-propyl ester
121. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-(4-methyl-piperazin-1-yl)-propyl ester
122. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester
123. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-nitro-phenoxy)-ethyl ester
124. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-pyridin-2-yl-propyl ester
125. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-pyridin-3-yl-propyl ester
126. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-4-yl-ethyl ester
127. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester
128. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester
129. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester
130. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-piperidin-1-yl-ethyl ester
131. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid carboxymethyl ester
132. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-methyl-piperazin-1-yl)-ethyl ester
133. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methoxycarbonylmethyl ester
134. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-acetylamino-ethyl ester
135. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-hydroxy-ethyl ester
136. 3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-imidazol-1-yl-ethyl ester
137. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
138. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester
139. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester
140. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester
141. 3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester
142. 2-[(E)-3-(2-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
143. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 4-methoxy-phenyl ester
144. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid benzyl ester
145. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid propyl ester
146. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(4-methoxy-phenyl)-ethyl ester
147. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-methoxy-benzyl ester
148. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-phenyl-propyl ester
149. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester
150. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester
151. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 4-methoxycarbonyl-phenyl ester
152. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(3-methoxy-phenyl)-ethyl ester
153. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-(2-methoxy-phenyl)-ethyl ester
154. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-yl ester
155. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid methyl ester
156. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-morpholin-4-yl-ethyl ester
157. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-pyridin-3-yl-propyl ester
158. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester
159. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-3-yl-ethyl ester
160. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester
161. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethoxycarbonylmethyl ester
162. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxycarbonyl-ethyl ester
163. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 3-dimethylamino-propyl ester
164. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester
165. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2,3-dihydroxy-propyl ester
166. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-benzyloxy-ethyl ester
167. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
168. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid cyclohexyl ester
169. (E)-N-(6-Acetyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
170. (E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide
171. (E)-N-[3-Cyano-6-(3-1H-indol-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
172. (E)-N-[3-Cyano-6-(4-1H-indol-3-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
173. 4-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyric acid methyl ester
174. (E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
175. (E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-acrylamide
176. 3-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-3-oxo-propionic acid ethyl ester
177. (E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
178. 4-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-N,N-dimethyl-4-oxo-butyramide
179. (E)-N-[3-Cyano-6-(3-ureido-propanoyl)-4,5,6,7-tetrahydro-thieno [2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
180. (E)-N-[3-Cyano-6-(3-guanidino-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
181. (E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
182. (E)-N-[3-Cyano-6-(2-1H-indol-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
183. (E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
184. (E)-N-{3-Cyano-6-[4-(4-methanesulfonyl-phenyl)-4-oxo-butanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-acrylamide
185. (E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
186. 5-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-5-oxo-pentanoic acid methyl ester
187. (E)-N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
188. (E)-N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
189. Acetic acid 2-[3-cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxo-ethyl ester
190. (E)-N-[3-Cyano-6-(4-imidazol-1-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
191. Acetic acid 4-[3-cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyl ester
192. (E)-N-[3-Cyano-6-(4-hydroxy-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide
193. (E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
194. (E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
195. (E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
196. (E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
197. (E)-N-[3-Cyano-6-(3-[1,2,4]triazol-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
198. (E)-N-[3-Cyano-6-(3-thiazol-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
199. 4-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyric acid
200. (E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-pyridin-3-yl-acrylamide
201. {3-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-3-oxo-propyl}-carbamic acid tert-butyl ester
202. {4-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyl}-carbamic acid tert-butyl ester
203. {2-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester
204. (E)-N-[6-(4-Amino-butanoyl)-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
205. (E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide
206. (E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide
207. (E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide
208. (E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide
209. (E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-acrylamide
210. (E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide
211. (E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide
212. (E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide
213. (E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide
214. (E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide
215. (E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide
216. (E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
217. (E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-acrylamide
218. (E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
219. (E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
220. (E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
221. (E)-N-[3-Cyano-6-(3-phenyl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
222. (E)-N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
223. (E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
224. (E)-N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide
225. (E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamide
226. (E)-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-acrylamide
227. (E)-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-acrylamide
228. (E)-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-acrylamide
229. (E)-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-acrylamide
230. 3-Cyano-2-[(E)-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
231. 3-Cyano-2-{(E)-3-[2-(1,1-difluoro-methoxy)-phenyl]-allanoylamino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
232. 2-[(E)-3-(4-Bromo-benzo[1,3]dioxol-5-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
233. 3-Cyano-2-[(E)-3-(2-trifluoromethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
234. 3-Cyano-2-((E)-3-2,3-dihydro-benzofuran-7-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester
235. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
236. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester
237. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester
238. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-ylmethyl ester
239. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester
240. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-methoxy-ethyl ester
241. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-2-ylmethyl ester
242. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-3-ylmethyl ester
243. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid 2-pyridin-2-yl-ethyl ester
244. 3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid pyridin-4-yl-methyl ester
245. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid ethylamide
246. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
247. 3-Cyano-2-[(E)-3-(furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-ethyl ester
248. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-(2-pyridin-4-yl-ethyl) ester
249. 3-Cyano-2-[(E)-3-(furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-(2-pyridin-4-yl-ethyl) ester
250. 3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-(2-pyridin-2-yl-ethyl) ester
251. 3-Cyano-2-[(E)-3-(furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic acid S-(2-pyridin-2-yl-ethyl) ester.

248 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/411,740Filed 26 Mar 2009 · division
Priority: 20 Nov 2006
Published: US 2009/0270378 A129 Oct 2009
Granted: 28 Sep 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 495/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
A61P 35/04
Antineoplastic agents: specific for metastasis
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Application11/597,142Parent of this division · filed 20 Nov 2006
US 2009/0270378 A1Pre-grant publication · published 29 Oct 2009
US 7,723,523 B2Parent of this division
US 2007/0244112 A1Published application
US 7,803,945 B2This patent

From the US filing history. Foreign family members aren’t listed.

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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/or apoptosis inducing activity.

wherein
Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, or —C(O)N(R3)R4;
Rb is Q-2-4C-alkenyl, in which
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;
in which
R1, R2 and R3 are the same or different and are independently selected from the group consisting of:
hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R5;
each R4 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted by at least one substituent independently selected from R5;
R5, Rba, Rbb, Rbc, Rca and Rcb are the same or different and are independently selected from the group consisting of:
1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,
halogen, trifluoromethyl, nitro, cyano, guanidino, amidino,
—C(O)R6, —C(O)OR7, —C(O)N(R8)R9, —S(O)2R6, —S(O)2N(R8)R9,
—N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9, —N(R10)S(O)2R6,
—N(R10)S(O)2N(R8)R9,
—OC(O)R6, —OC(O)N(R8)R9,
—OR7, —N(R8)R9 and —SR7,
wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R11;
R6, R7 and R8 are the same or different and are independently selected from the group consisting of:
hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by at least one substituent independently selected from R12;
each R9 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted by at least one substituent independently selected from R12;
each R10 is independently selected from the group consisting of:
hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl;
R11 is R5;
each R12 is independently selected from R5;
each Ar is independently selected from the group consisting of phenyl and naphthyl;
each Har is the same or different and independently a fully aromatic or partially aromatic mono- or fused bicyclic ring or ring system, which contains at least on heteroatom in the ring or ring system, wherein Har is 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 is attached via a substitutable ring carbon or ring nitrogen atom of Har;
each Het 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,
wherein the 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 benzo group, a 3-7C-cycloalkane group, or an additional heterocyclic ring B,
wherein said Het is attached via a substitutable ring carbon or ring nitrogen atom.

35 more elements

Facts

Application

12/411,740Filed 26 Mar 2009 · division

Priority

20 Nov 2006

Published

US 2009/0270378 A129 Oct 2009

Granted

28 Sep 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 495/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
A61P 35/04
Antineoplastic agents: specific for metastasis
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00