BRPI0719221A2 - Derivados de pirrolidina como inibidores de iap - Google Patents
Derivados de pirrolidina como inibidores de iap Download PDFInfo
- Publication number
- BRPI0719221A2 BRPI0719221A2 BRPI0719221-5A BRPI0719221A BRPI0719221A2 BR PI0719221 A2 BRPI0719221 A2 BR PI0719221A2 BR PI0719221 A BRPI0719221 A BR PI0719221A BR PI0719221 A2 BRPI0719221 A2 BR PI0719221A2
- Authority
- BR
- Brazil
- Prior art keywords
- pyrrolidin
- methylamino
- cyclohexyl
- propionamide
- ethyl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title description 2
- 150000003235 pyrrolidines Chemical class 0.000 title 1
- 229940080818 propionamide Drugs 0.000 claims description 240
- -1 mercapto, sulfo Chemical group 0.000 claims description 227
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 125000003118 aryl group Chemical group 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 239000000460 chlorine Substances 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000001589 carboacyl group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 3
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- BUMQMCDLYZAZNA-UHFFFAOYSA-N n'-methylpropanehydrazide Chemical compound CCC(=O)NNC BUMQMCDLYZAZNA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- TXHPORRYUKITDP-UHFFFAOYSA-N sulfamoylsulfamic acid Chemical compound NS(=O)(=O)NS(O)(=O)=O TXHPORRYUKITDP-UHFFFAOYSA-N 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims 5
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 3
- LSMBOQAQZPPBCL-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(1h-indol-3-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C3=CC=CC=C3NC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 LSMBOQAQZPPBCL-UHFFFAOYSA-N 0.000 claims 2
- XAYZUCXGUHTJRQ-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(2-isoquinolin-4-ylpyridin-4-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(N=CC=2)C=2C3=CC=CC=C3C=NC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 XAYZUCXGUHTJRQ-UHFFFAOYSA-N 0.000 claims 2
- FVAHQZJOBROOQE-UHFFFAOYSA-N 2-(methylamino)-n-[3-methyl-1-[2-[2-(3-methylindol-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-1-oxobutan-2-yl]propanamide Chemical compound CNC(C)C(=O)NC(C(C)C)C(=O)N1CCCC1C1=CC=NC(N2C3=CC=CC=C3C(C)=C2)=C1 FVAHQZJOBROOQE-UHFFFAOYSA-N 0.000 claims 1
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 claims 1
- VXFMMEINZOLOJN-UHFFFAOYSA-N 3-[5-[1-[2-cyclohexyl-2-[2-(methylamino)propanoylamino]acetyl]pyrrolidin-2-yl]pyridin-3-yl]-n,n-dimethylindole-1-carboxamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C3=CC=CC=C3N(C(=O)N(C)C)C=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 VXFMMEINZOLOJN-UHFFFAOYSA-N 0.000 claims 1
- NIXTXVUBGUOWBD-UHFFFAOYSA-N 3-[6-[1-[2-cyclohexyl-2-[2-(methylamino)propanoylamino]acetyl]pyrrolidin-2-yl]pyrimidin-4-yl]-n,n-dimethylindole-1-carboxamide Chemical compound C1CCC(C=2N=CN=C(C=2)C=2C3=CC=CC=C3N(C(=O)N(C)C)C=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 NIXTXVUBGUOWBD-UHFFFAOYSA-N 0.000 claims 1
- 150000007945 N-acyl ureas Chemical class 0.000 claims 1
- 125000002431 aminoalkoxy group Chemical group 0.000 claims 1
- 230000009702 cancer cell proliferation Effects 0.000 claims 1
- LHTMPBRWDGGNAC-UHFFFAOYSA-N n-[1-[2-[2-(6-fluoroindol-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-(methylamino)propanamide Chemical compound CNC(C)C(=O)NC(C(C)C)C(=O)N1CCCC1C1=CC=NC(N2C3=CC(F)=CC=C3C=C2)=C1 LHTMPBRWDGGNAC-UHFFFAOYSA-N 0.000 claims 1
- FUQJVCQDMIKMLZ-UHFFFAOYSA-N n-[1-[2-[2-(benzimidazol-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-(methylamino)propanamide Chemical compound CNC(C)C(=O)NC(C(C)C)C(=O)N1CCCC1C1=CC=NC(N2C3=CC=CC=C3N=C2)=C1 FUQJVCQDMIKMLZ-UHFFFAOYSA-N 0.000 claims 1
- PABVNKBDVGYEGT-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(1h-indol-2-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2NC3=CC=CC=C3C=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 PABVNKBDVGYEGT-UHFFFAOYSA-N 0.000 claims 1
- YWHNNGLUPMDTAP-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(2-indazol-1-ylpyridin-4-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(N=CC=2)N2C3=CC=CC=C3C=N2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 YWHNNGLUPMDTAP-UHFFFAOYSA-N 0.000 claims 1
- XGAQLJAHEOQJEK-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(5-indazol-1-ylpyridin-3-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)N2C3=CC=CC=C3C=N2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 XGAQLJAHEOQJEK-UHFFFAOYSA-N 0.000 claims 1
- QEHNETHUVPZVRJ-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(5-indol-1-ylpyridin-3-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)N2C3=CC=CC=C3C=C2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 QEHNETHUVPZVRJ-UHFFFAOYSA-N 0.000 claims 1
- DARHYVJGJLVNAH-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(5-naphthalen-1-ylpyridin-3-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C3=CC=CC=C3C=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 DARHYVJGJLVNAH-UHFFFAOYSA-N 0.000 claims 1
- NPQDDJGXKMNGIB-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(5-naphthalen-2-ylpyridin-3-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C=C3C=CC=CC3=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 NPQDDJGXKMNGIB-UHFFFAOYSA-N 0.000 claims 1
- WJJLAEHIBHIQTF-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-(6-indol-1-ylpyrimidin-4-yl)pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=CN=C(C=2)N2C3=CC=CC=C3C=C2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 WJJLAEHIBHIQTF-UHFFFAOYSA-N 0.000 claims 1
- RYQZLLHAEKDYPO-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[2-(5-fluoro-2,3-dihydroindol-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(N=CC=2)N2C3=CC=C(F)C=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 RYQZLLHAEKDYPO-UHFFFAOYSA-N 0.000 claims 1
- OBLWQJQGEVUUAC-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[2-(6-fluoro-2,3-dihydroindol-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(N=CC=2)N2C3=CC(F)=CC=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 OBLWQJQGEVUUAC-UHFFFAOYSA-N 0.000 claims 1
- JFTXWJNBANATPA-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[2-(6-fluoro-3,4-dihydro-2h-quinolin-1-yl)pyridin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(N=CC=2)N2C3=CC=C(F)C=C3CCC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 JFTXWJNBANATPA-UHFFFAOYSA-N 0.000 claims 1
- JTOWFBKWYKKKGN-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[2-methyl-6-(2-methylphenyl)pyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=C(C)N=C(C=2)C=2C(=CC=CC=2)C)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 JTOWFBKWYKKKGN-UHFFFAOYSA-N 0.000 claims 1
- JDFZCHCBSAUWRF-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[4-(5-fluoro-2,3-dihydroindol-1-yl)pyridin-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=CC=C(C=2)N2C3=CC=C(F)C=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 JDFZCHCBSAUWRF-UHFFFAOYSA-N 0.000 claims 1
- HMIOFHDDBLYHBH-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[5-(2-methylphenyl)pyridin-3-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C(=CC=CC=2)C)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 HMIOFHDDBLYHBH-UHFFFAOYSA-N 0.000 claims 1
- ODAZZDHNXJTOEM-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[5-(3-methylphenyl)pyridin-3-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C=C(C)C=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 ODAZZDHNXJTOEM-UHFFFAOYSA-N 0.000 claims 1
- FHVDRECTOYZHFS-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[5-(4-fluorophenyl)pyridin-3-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C=CC(F)=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 FHVDRECTOYZHFS-UHFFFAOYSA-N 0.000 claims 1
- VYSMMNAWNFFIFE-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[5-(4-methylphenyl)pyridin-3-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C=CC(C)=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 VYSMMNAWNFFIFE-UHFFFAOYSA-N 0.000 claims 1
- NXDAGBCECRKCGY-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[5-(5-fluoro-2,3-dihydroindol-1-yl)pyridin-3-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)N2C3=CC=C(F)C=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 NXDAGBCECRKCGY-UHFFFAOYSA-N 0.000 claims 1
- XQILTTPTKSWFGF-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[6-(1h-indol-3-yl)-2-methylpyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=C(C)N=C(C=2)C=2C3=CC=CC=C3NC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 XQILTTPTKSWFGF-UHFFFAOYSA-N 0.000 claims 1
- IVMUAGOPSXOMJW-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[6-(2,3-dihydroindol-1-yl)-2-methylpyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=C(C)N=C(C=2)N2C3=CC=CC=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 IVMUAGOPSXOMJW-UHFFFAOYSA-N 0.000 claims 1
- AEOVQBQKSAHDAB-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[6-(2-methylphenyl)pyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=CN=C(C=2)C=2C(=CC=CC=2)C)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 AEOVQBQKSAHDAB-UHFFFAOYSA-N 0.000 claims 1
- OEGRLTUDZRPJQO-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[6-(5-fluoro-2,3-dihydroindol-1-yl)pyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=CN=C(C=2)N2C3=CC=C(F)C=C3CC2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 OEGRLTUDZRPJQO-UHFFFAOYSA-N 0.000 claims 1
- SIRHPGRSGCAACR-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[6-(5-fluoro-3-methylindol-1-yl)-2-methylpyrimidin-4-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2N=C(C)N=C(C=2)N2C3=CC=C(F)C=C3C(C)=C2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 SIRHPGRSGCAACR-UHFFFAOYSA-N 0.000 claims 1
- NODCRGNTDODBIR-UHFFFAOYSA-N n-[1-cyclohexyl-2-[2-[7-(4-fluorophenyl)-1,3-benzothiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2SC3=C(C=4C=CC(F)=CC=4)C=CC=C3N=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 NODCRGNTDODBIR-UHFFFAOYSA-N 0.000 claims 1
- OUHAEMWXPWJNIQ-UHFFFAOYSA-N n-[1-cyclohexyl-2-oxo-2-[2-(1-phenylisoquinolin-7-yl)pyrrolidin-1-yl]ethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C3C(C=4C=CC=CC=4)=NC=CC3=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 OUHAEMWXPWJNIQ-UHFFFAOYSA-N 0.000 claims 1
- YDIHYDFUZAPBPN-UHFFFAOYSA-N n-[1-cyclohexyl-2-oxo-2-[2-(5-pyridin-2-ylpyridin-3-yl)pyrrolidin-1-yl]ethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2N=CC=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 YDIHYDFUZAPBPN-UHFFFAOYSA-N 0.000 claims 1
- YEYOELVULLXEEQ-UHFFFAOYSA-N n-[1-cyclohexyl-2-oxo-2-[2-(5-pyridin-3-ylpyridin-3-yl)pyrrolidin-1-yl]ethyl]-2-(methylamino)propanamide Chemical compound C1CCC(C=2C=C(C=NC=2)C=2C=NC=CC=2)N1C(=O)C(NC(=O)C(C)NC)C1CCCCC1 YEYOELVULLXEEQ-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US82923406P | 2006-10-12 | 2006-10-12 | |
| US60/829,234 | 2006-10-12 | ||
| PCT/US2007/080875 WO2008045905A1 (en) | 2006-10-12 | 2007-10-10 | Pyrrolydine derivatives as iap inhibitors |
Publications (1)
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|---|---|
| BRPI0719221A2 true BRPI0719221A2 (pt) | 2014-03-18 |
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|---|---|---|---|
| BRPI0719221-5A BRPI0719221A2 (pt) | 2006-10-12 | 2007-10-10 | Derivados de pirrolidina como inibidores de iap |
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| Country | Link |
|---|---|
| US (1) | US8044209B2 (enExample) |
| EP (1) | EP2102229B1 (enExample) |
| JP (1) | JP5190062B2 (enExample) |
| KR (1) | KR20090065548A (enExample) |
| CN (1) | CN101595121A (enExample) |
| AU (1) | AU2007307763A1 (enExample) |
| BR (1) | BRPI0719221A2 (enExample) |
| CA (1) | CA2666112A1 (enExample) |
| MX (1) | MX2009003834A (enExample) |
| RU (1) | RU2009117701A (enExample) |
| WO (1) | WO2008045905A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120127754A (ko) | 2004-12-20 | 2012-11-23 | 제넨테크, 인크. | Ｉａｐ의 피롤리딘 억제제 |
| JP4954983B2 (ja) | 2005-05-18 | 2012-06-20 | ファーマサイエンス・インコーポレイテッド | Ｂｉｒドメイン結合化合物 |
| RU2418807C2 (ru) | 2005-10-25 | 2011-05-20 | Аегера Терапьютикс Инк. | Соединения, связывающие bir домены iap |
| RU2451025C2 (ru) | 2005-12-19 | 2012-05-20 | Дженентек, Инк. | Ингибиторы iap |
| TWI543988B (zh) | 2006-03-16 | 2016-08-01 | 科學製藥股份有限公司 | 結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物 |
| US8110681B2 (en) | 2006-03-17 | 2012-02-07 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Compounds for the treatment of spinal muscular atrophy and other uses |
| SG10201407457UA (en) | 2006-05-16 | 2014-12-30 | Pharmascience Inc | Iap bir domain binding compounds |
| PE20110218A1 (es) * | 2006-08-02 | 2011-04-01 | Novartis Ag | DERIVADOS DE 2-OXO-ETIL-AMINO-PROPIONAMIDA-PIRROLIDIN-2-IL-SUSTITUIDOS COMO INHIBIDORES DEL ENLACE DE LA PROTEINA Smac AL INHIBIDOR DE LA PROTEINA DE APOPTOSIS |
| RU2466131C2 (ru) * | 2006-12-19 | 2012-11-10 | Дженентек, Инк. | Имидазопиридиновые ингибиторы iap |
| NZ598890A (en) | 2007-04-30 | 2013-10-25 | Genentech Inc | Inhibitors of iap |
| WO2009140447A1 (en) * | 2008-05-16 | 2009-11-19 | Novartis Ag | Immunomodulation by iap inhibitors |
| CA2730448A1 (en) | 2008-08-02 | 2010-02-11 | Genentech, Inc. | Inhibitors of iap |
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|---|---|---|---|---|
| EP1283827A2 (en) | 2000-05-23 | 2003-02-19 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
| US7718600B2 (en) * | 2000-09-29 | 2010-05-18 | The Trustees Of Princeton University | IAP binding compounds |
| CN100384819C (zh) | 2002-07-02 | 2008-04-30 | 诺瓦提斯公司 | 与细胞凋亡蛋白抑制剂结合的smac蛋白的肽抑制剂 |
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| CA2570321C (en) | 2004-07-02 | 2013-10-08 | Genentech, Inc. | Inhibitors of iap |
| KR20120127754A (ko) | 2004-12-20 | 2012-11-23 | 제넨테크, 인크. | Ｉａｐ의 피롤리딘 억제제 |
| RU2451025C2 (ru) * | 2005-12-19 | 2012-05-20 | Дженентек, Инк. | Ингибиторы iap |
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2007
- 2007-10-10 US US12/445,435 patent/US8044209B2/en not_active Expired - Fee Related
- 2007-10-10 EP EP07844058.3A patent/EP2102229B1/en not_active Not-in-force
- 2007-10-10 JP JP2009532544A patent/JP5190062B2/ja not_active Expired - Fee Related
- 2007-10-10 WO PCT/US2007/080875 patent/WO2008045905A1/en not_active Ceased
- 2007-10-10 RU RU2009117701/04A patent/RU2009117701A/ru not_active Application Discontinuation
- 2007-10-10 CN CNA2007800458268A patent/CN101595121A/zh active Pending
- 2007-10-10 KR KR1020097009617A patent/KR20090065548A/ko not_active Withdrawn
- 2007-10-10 AU AU2007307763A patent/AU2007307763A1/en not_active Abandoned
- 2007-10-10 BR BRPI0719221-5A patent/BRPI0719221A2/pt not_active Application Discontinuation
- 2007-10-10 MX MX2009003834A patent/MX2009003834A/es unknown
- 2007-10-10 CA CA002666112A patent/CA2666112A1/en not_active Abandoned
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|---|---|
| US8044209B2 (en) | 2011-10-25 |
| EP2102229A1 (en) | 2009-09-23 |
| JP5190062B2 (ja) | 2013-04-24 |
| RU2009117701A (ru) | 2010-11-20 |
| WO2008045905A1 (en) | 2008-04-17 |
| MX2009003834A (es) | 2009-04-22 |
| AU2007307763A1 (en) | 2008-04-17 |
| KR20090065548A (ko) | 2009-06-22 |
| CA2666112A1 (en) | 2008-04-17 |
| CN101595121A (zh) | 2009-12-02 |
| US20110015232A1 (en) | 2011-01-20 |
| JP2010506847A (ja) | 2010-03-04 |
| EP2102229B1 (en) | 2014-03-26 |
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