KR20140042814A - 신규의 헥사하이드로사이클로펜타피롤론, 헥사하이드로피롤로피롤론, 옥타하이드로피롤로피리딘온 및 옥타하이드로피리딘온 화합물 - Google Patents
신규의 헥사하이드로사이클로펜타피롤론, 헥사하이드로피롤로피롤론, 옥타하이드로피롤로피리딘온 및 옥타하이드로피리딘온 화합물 Download PDFInfo
- Publication number
- KR20140042814A KR20140042814A KR1020137033414A KR20137033414A KR20140042814A KR 20140042814 A KR20140042814 A KR 20140042814A KR 1020137033414 A KR1020137033414 A KR 1020137033414A KR 20137033414 A KR20137033414 A KR 20137033414A KR 20140042814 A KR20140042814 A KR 20140042814A
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- trifluoromethoxy
- pyrrolo
- octahydro
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 179
- DSILUGCORMLHPA-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,2-b]pyrrol-5-one Chemical compound N1CCC2NC(=O)CC21 DSILUGCORMLHPA-UHFFFAOYSA-N 0.000 title 1
- PMGSPDVTAKHCLW-UHFFFAOYSA-N 3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[b]pyrrol-2-one Chemical compound C1CCC2NC(=O)CC21 PMGSPDVTAKHCLW-UHFFFAOYSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 109
- -1 2-hydroxy-phenyl Chemical group 0.000 claims description 75
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 238000011282 treatment Methods 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 230000002265 prevention Effects 0.000 claims description 38
- 206010012601 diabetes mellitus Diseases 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 25
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 25
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 201000001320 Atherosclerosis Diseases 0.000 claims description 20
- 208000008589 Obesity Diseases 0.000 claims description 20
- 230000005856 abnormality Effects 0.000 claims description 20
- 230000002107 myocardial effect Effects 0.000 claims description 20
- 235000020824 obesity Nutrition 0.000 claims description 20
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 19
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 206010061218 Inflammation Diseases 0.000 claims description 19
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 19
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 19
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 19
- 230000004054 inflammatory process Effects 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 102000000019 Sterol Esterase Human genes 0.000 claims description 15
- 108010055297 Sterol Esterase Proteins 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- TZYWCWPNWKEQCG-ANEWXZNUSA-N (3ar,7as)-2-[2-(2,4-dichlorophenyl)-2-hydroxyethyl]-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)CC(O)C=2C(=CC(Cl)=CC=2)Cl)CN1C1=CC=C(OCC(F)(F)F)C=C1 TZYWCWPNWKEQCG-ANEWXZNUSA-N 0.000 claims description 4
- OOPXPUHSUWIQHN-PBHICJAKSA-N (3ar,7as)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-[2-(trifluoromethoxy)phenyl]sulfonyl-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)OC(F)(F)F)C[C@H]2CC1 OOPXPUHSUWIQHN-PBHICJAKSA-N 0.000 claims description 4
- ICURKDZAOKAZKG-OWQGQXMQSA-N (3as,5s,6ar)-5-(butoxymethyl)-5-hydroxy-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@@](C[C@@H]1C1=O)(O)COCCCC)N1C1=CC=C(OC(F)(F)F)C=C1 ICURKDZAOKAZKG-OWQGQXMQSA-N 0.000 claims description 4
- RUZIVNMLRPKBGI-KUBVQFIISA-N (3as,7ar)-1-(2-phenylacetyl)-5-[4-(trifluoromethoxy)phenyl]-2,3,3a,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@H](CNC2C(=O)CC=3C=CC=CC=3)[C@H]2CC1 RUZIVNMLRPKBGI-KUBVQFIISA-N 0.000 claims description 4
- IOHFWOZJENTFLA-XJKSGUPXSA-N (3as,7ar)-2-(2-chlorophenyl)sulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@@H]2CC1 IOHFWOZJENTFLA-XJKSGUPXSA-N 0.000 claims description 4
- 208000006454 hepatitis Diseases 0.000 claims description 4
- 231100000283 hepatitis Toxicity 0.000 claims description 4
- ZCLNJVVEHPLNDO-BSBHGOPBSA-N n-[(3as,6ar)-3-oxo-2-[4-(trifluoromethoxy)phenyl]-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrol-5-yl]-2-chlorobenzenesulfonamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@H]2CC(NS(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@H]2C1 ZCLNJVVEHPLNDO-BSBHGOPBSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- JWCAWYZVCBQCHU-PBHICJAKSA-N (3ar,7as)-2-(2-chlorophenyl)sulfonyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@H]2CC1 JWCAWYZVCBQCHU-PBHICJAKSA-N 0.000 claims description 3
- SNVFIFXXEAAXLK-XPFLZZBLSA-N (3as,6ar)-5-hydroxy-5-propyl-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1CC(C[C@@H]1C1=O)(O)CCC)N1C1=CC=C(OC(F)(F)F)C=C1 SNVFIFXXEAAXLK-XPFLZZBLSA-N 0.000 claims description 3
- MFAMMXPGEWSZTR-KBXCAEBGSA-N (3as,7ar)-2-(4-fluorobenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 MFAMMXPGEWSZTR-KBXCAEBGSA-N 0.000 claims description 3
- DXVHIIDHQSBIDF-HNAYVOBHSA-N (3as,7ar)-2-[(4-fluorophenyl)methyl]-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1CN1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 DXVHIIDHQSBIDF-HNAYVOBHSA-N 0.000 claims description 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- SDRXORFVMCHESD-CHEUHSMRSA-N (3ar,7as)-1-(2-phenylacetyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3,3a,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@@H](CNC2C(=O)CC=3C=CC=CC=3)[C@@H]2CC1 SDRXORFVMCHESD-CHEUHSMRSA-N 0.000 claims description 2
- URZPTRWITOLAHH-CJNGLKHVSA-N (3ar,7as)-2-(2-chloropyridin-3-yl)sulfonyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=NC=CC=3)Cl)C[C@H]2CC1 URZPTRWITOLAHH-CJNGLKHVSA-N 0.000 claims description 2
- TUTZPAJFLXAIQH-PBHICJAKSA-N (3ar,7as)-2-(3,3-dimethylbutanoyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)CC(C)(C)C)CN1C1=CC=C(OCC(F)(F)F)C=C1 TUTZPAJFLXAIQH-PBHICJAKSA-N 0.000 claims description 2
- QLGSFDRAOBTLSJ-BEFAXECRSA-N (3ar,7as)-2-(benzenesulfonyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C=CC=CC=3)C[C@H]2CC1 QLGSFDRAOBTLSJ-BEFAXECRSA-N 0.000 claims description 2
- BMTUEDGSYHQHFI-NQIIRXRSSA-N (3ar,7as)-2-[2-(4-methylphenyl)acetyl]-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(C)=CC=C1CC(=O)N1C[C@@H]2C(=O)N(C=3C=CC(OCC(F)(F)F)=CC=3)CC[C@@H]2C1 BMTUEDGSYHQHFI-NQIIRXRSSA-N 0.000 claims description 2
- BWVIKPJQQKIUGB-PBHICJAKSA-N (3ar,7as)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-[2-(trifluoromethyl)phenyl]sulfonyl-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)C(F)(F)F)C[C@H]2CC1 BWVIKPJQQKIUGB-PBHICJAKSA-N 0.000 claims description 2
- ZOSXIEYYQRCFQH-XEGUGMAKSA-N (3as,5s,6ar)-5-hydroxy-5-(2,2,2-trifluoroethoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@](C[C@@H]1C1=O)(COCC(F)(F)F)O)N1C1=CC=C(OC(F)(F)F)C=C1 ZOSXIEYYQRCFQH-XEGUGMAKSA-N 0.000 claims description 2
- FWMIDUCEURWGLJ-DCPHZVHLSA-N (3as,5s,6ar)-5-hydroxy-5-(phenoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@]1(O)C[C@@H]2C(=O)N(C[C@@H]2C1)C=1C=CC(OC(F)(F)F)=CC=1)OC1=CC=CC=C1 FWMIDUCEURWGLJ-DCPHZVHLSA-N 0.000 claims description 2
- UQTFGVGNOYPZBT-NUTKFTJISA-N (3as,5s,6ar)-5-hydroxy-5-(propoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@@](C[C@@H]1C1=O)(O)COCCC)N1C1=CC=C(OC(F)(F)F)C=C1 UQTFGVGNOYPZBT-NUTKFTJISA-N 0.000 claims description 2
- JQQBOTWLJXCTBZ-KEXXGOCASA-N (3as,6ar)-5-(anilinomethyl)-5-hydroxy-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C(=O)N(C[C@@H]1C1)C=2C=CC(OC(F)(F)F)=CC=2)C1(O)CNC1=CC=CC=C1 JQQBOTWLJXCTBZ-KEXXGOCASA-N 0.000 claims description 2
- NGLACRZGEXFSMJ-SJKOYZFVSA-N (3as,6as)-4-oxo-n,5-bis[4-(trifluoromethoxy)phenyl]-3,3a,6,6a-tetrahydro-1h-pyrrolo[3,4-c]pyrrole-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)C[C@H]2C1 NGLACRZGEXFSMJ-SJKOYZFVSA-N 0.000 claims description 2
- BVXPXCFIGDWPIB-DNVCBOLYSA-N (3as,6as)-5-(4-ethylphenyl)-4-oxo-n-[4-(trifluoromethoxy)phenyl]-3,3a,6,6a-tetrahydro-1h-pyrrolo[3,4-c]pyrrole-2-carboxamide Chemical compound C1=CC(CC)=CC=C1N1C(=O)[C@@H]2CN(C(=O)NC=3C=CC(OC(F)(F)F)=CC=3)C[C@@H]2C1 BVXPXCFIGDWPIB-DNVCBOLYSA-N 0.000 claims description 2
- UTWATDQGGKALAL-SUMWQHHRSA-N (3as,7ar)-2-(2-chlorobenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(C(=O)C=3C(=CC=CC=3)Cl)C[C@@H]2CC1 UTWATDQGGKALAL-SUMWQHHRSA-N 0.000 claims description 2
- YXAQHOMOMXWBST-XJKSGUPXSA-N (3as,7ar)-2-(2-methylpropylsulfonyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)S(=O)(=O)CC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 YXAQHOMOMXWBST-XJKSGUPXSA-N 0.000 claims description 2
- FIADIBYFRWITEN-XJKSGUPXSA-N (3as,7ar)-2-(3-methylbutanoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)C(=O)CC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 FIADIBYFRWITEN-XJKSGUPXSA-N 0.000 claims description 2
- TWMYWSDGOVHDKS-WMLDXEAASA-N (3as,7ar)-2-(3-methylbutylsulfonyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)S(=O)(=O)CCC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 TWMYWSDGOVHDKS-WMLDXEAASA-N 0.000 claims description 2
- WPSQOKLLQVOTBZ-SCLBCKFNSA-N (3as,7ar)-2-(4-fluorophenyl)sulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 WPSQOKLLQVOTBZ-SCLBCKFNSA-N 0.000 claims description 2
- UVQXTGZXMGDYMH-GHTZIAJQSA-N (3as,7ar)-2-(4-propan-2-ylbenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(C(C)C)=CC=C1C(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 UVQXTGZXMGDYMH-GHTZIAJQSA-N 0.000 claims description 2
- ABDCELHRYJDOPX-QFBILLFUSA-N (3as,7ar)-2-benzylsulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(S(=O)(=O)CC=3C=CC=CC=3)C[C@@H]2CC1 ABDCELHRYJDOPX-QFBILLFUSA-N 0.000 claims description 2
- VTFOQHWGMPFGSF-SCLBCKFNSA-N (3as,7ar)-4-oxo-n,5-bis[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 VTFOQHWGMPFGSF-SCLBCKFNSA-N 0.000 claims description 2
- RPGIAZHLHQUFBN-SCLBCKFNSA-N (3as,7ar)-n-(4-fluorophenyl)-4-oxo-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 RPGIAZHLHQUFBN-SCLBCKFNSA-N 0.000 claims description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- SDRNBXQJIXBCGH-QWLMFLSESA-N 2-[(3ar,7as)-4-oxo-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-2-yl]-n-(4-fluorophenyl)-3-methylbutanamide Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(C(C)C)C(=O)NC=2C=CC(F)=CC=2)CN1C1=CC=C(OCC(F)(F)F)C=C1 SDRNBXQJIXBCGH-QWLMFLSESA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- NYMDZLNOQPHCMN-CJNGLKHVSA-N tert-butyl (3ar,7as)-4-oxo-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)OC(C)(C)C)CN1C1=CC=C(OCC(F)(F)F)C=C1 NYMDZLNOQPHCMN-CJNGLKHVSA-N 0.000 claims description 2
- LMSUQMJAMATPBV-DOMZBBRYSA-N tert-butyl (3ar,7as)-4-oxo-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)OC(C)(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 LMSUQMJAMATPBV-DOMZBBRYSA-N 0.000 claims description 2
- 208000010706 fatty liver disease Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 103
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 55
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11166437 | 2011-05-17 | ||
| EP11166437.1 | 2011-05-17 | ||
| PCT/EP2012/058852 WO2012156339A1 (en) | 2011-05-17 | 2012-05-14 | New hexahydrocyclopentapyrrolone, hexahydropyrrolopyrrolone, octahydropyrrolopyridinone and octahydropyridinone compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140042814A true KR20140042814A (ko) | 2014-04-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020137033414A Withdrawn KR20140042814A (ko) | 2011-05-17 | 2012-05-14 | 신규의 헥사하이드로사이클로펜타피롤론, 헥사하이드로피롤로피롤론, 옥타하이드로피롤로피리딘온 및 옥타하이드로피리딘온 화합물 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8501768B2 (https=) |
| EP (1) | EP2709984B1 (https=) |
| JP (1) | JP2014513703A (https=) |
| KR (1) | KR20140042814A (https=) |
| CN (1) | CN103562180B (https=) |
| BR (1) | BR112013028368A2 (https=) |
| CA (1) | CA2832334A1 (https=) |
| ES (1) | ES2537591T3 (https=) |
| MX (1) | MX346980B (https=) |
| RU (1) | RU2013153898A (https=) |
| WO (1) | WO2012156339A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8497288B2 (en) * | 2011-05-09 | 2013-07-30 | Hoffmann-La Roche Inc. | Hexahydropyrroloimidazolone compounds |
| AR097794A1 (es) | 2013-09-26 | 2016-04-13 | Mnemosyne Pharmaceuticals Inc | Moduladores octahidro-ciclopenta[c]pirrol negativos de nr2b |
| JO3579B1 (ar) | 2014-09-26 | 2020-07-05 | Luc Therapeutics Inc | مُعدِلات تفاغرية سالبة لمستقبل nr2b من المركب n-ألكيل أريل-5-أوكسي أريل-ثامن هيدرو-خماسي الحلقة [c] بيرول |
| JP2018507900A (ja) * | 2015-03-13 | 2018-03-22 | アッヴィ・インコーポレイテッド | （インダゾール−４−イル）ヘキサヒドロピロロピロロン及び使用方法 |
| NZ754161A (en) | 2016-11-10 | 2025-11-28 | Keros Therapeutics Inc | Activin receptor type iia variants and methods of use thereof |
| IL320014A (en) | 2018-01-12 | 2025-06-01 | Keros Therapeutics Inc | Activin receptor type iib variants and methods of use thereof |
| WO2021189010A1 (en) | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| WO2021189019A1 (en) | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Activin receptor type ii chimeras and methods of use thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19942354A1 (de) * | 1999-09-04 | 2001-03-08 | Aventis Pharma Gmbh | Substituierte 3-Phenyl-5-alkoxi-1,3,4-oxdiazol-2-one, ihre Herstellung und Verwendung in Arzneimitteln |
| TR200401217T4 (tr) * | 2000-03-07 | 2004-06-21 | Aventis Pharma Deutschland Gmbh | İkameli 3-Fenil-5-Alkoksi-1,3,4-Oksdiazol-2-one (ve) hormona duyarlı lipazın önlenmesinde kullanılması |
| JP2004519435A (ja) * | 2000-12-01 | 2004-07-02 | ブリストル−マイヤーズ スクイブ カンパニー | 抗炎症性薬物として有用なヒダントイン化合物 |
| CN101115741A (zh) * | 2005-02-15 | 2008-01-30 | 诺和诺德公司 | 3,4-二氢-1h-异喹啉-2-羧酸5-氨基吡啶-2-基酯 |
| CN101336243A (zh) * | 2005-12-05 | 2008-12-31 | 因塞特公司 | 内酰胺化合物和其使用方法 |
| CN101432265B (zh) * | 2006-04-25 | 2011-12-14 | 伊莱利利公司 | 11-β-羟类固醇脱氢酶1的抑制剂 |
| BRPI0810858A2 (pt) * | 2007-04-27 | 2014-10-29 | Sanofi Aventis | Derivados de 2-heteroaril-pirrolo[3,4-c] pirrol e seus usos como inibidores de scd |
| US20120010186A1 (en) | 2009-03-23 | 2012-01-12 | Merck Frosst Canada Ltd. | Heterocyclic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| ME03452B (me) * | 2009-10-23 | 2020-01-20 | Janssen Pharmaceutica Nv | Disupstituisani oktahi-dropirolo[3,4-c]piroli kao modulatori oreksin receptora |
| UY33227A (es) * | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
-
2012
- 2012-05-04 US US13/463,863 patent/US8501768B2/en not_active Expired - Fee Related
- 2012-05-14 CN CN201280023662.XA patent/CN103562180B/zh not_active Expired - Fee Related
- 2012-05-14 WO PCT/EP2012/058852 patent/WO2012156339A1/en not_active Ceased
- 2012-05-14 ES ES12721814.7T patent/ES2537591T3/es active Active
- 2012-05-14 JP JP2014510758A patent/JP2014513703A/ja active Pending
- 2012-05-14 KR KR1020137033414A patent/KR20140042814A/ko not_active Withdrawn
- 2012-05-14 MX MX2013011628A patent/MX346980B/es active IP Right Grant
- 2012-05-14 CA CA2832334A patent/CA2832334A1/en not_active Abandoned
- 2012-05-14 BR BR112013028368A patent/BR112013028368A2/pt not_active IP Right Cessation
- 2012-05-14 EP EP12721814.7A patent/EP2709984B1/en not_active Not-in-force
- 2012-05-14 RU RU2013153898/04A patent/RU2013153898A/ru not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2537591T3 (es) | 2015-06-09 |
| CA2832334A1 (en) | 2012-11-22 |
| US8501768B2 (en) | 2013-08-06 |
| EP2709984A1 (en) | 2014-03-26 |
| BR112013028368A2 (pt) | 2017-01-24 |
| MX346980B (es) | 2017-04-07 |
| MX2013011628A (es) | 2013-10-25 |
| RU2013153898A (ru) | 2015-06-27 |
| WO2012156339A1 (en) | 2012-11-22 |
| HK1191942A1 (zh) | 2014-08-08 |
| US20120295934A1 (en) | 2012-11-22 |
| EP2709984B1 (en) | 2015-03-18 |
| JP2014513703A (ja) | 2014-06-05 |
| CN103562180B (zh) | 2016-04-20 |
| CN103562180A (zh) | 2014-02-05 |
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