EA031609B1 - Соединения и композиции для стимулирования хондрогенеза - Google Patents
Соединения и композиции для стимулирования хондрогенеза Download PDFInfo
- Publication number
- EA031609B1 EA031609B1 EA201692292A EA201692292A EA031609B1 EA 031609 B1 EA031609 B1 EA 031609B1 EA 201692292 A EA201692292 A EA 201692292A EA 201692292 A EA201692292 A EA 201692292A EA 031609 B1 EA031609 B1 EA 031609B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- carboxamide
- heptane
- oxabicyclo
- pyridin
- biphenyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 362
- 230000001939 inductive effect Effects 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title description 130
- 230000022159 cartilage development Effects 0.000 title description 9
- 238000000034 method Methods 0.000 claims abstract description 92
- 150000003839 salts Chemical class 0.000 claims abstract description 85
- 210000001612 chondrocyte Anatomy 0.000 claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 31
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims abstract description 28
- 230000004069 differentiation Effects 0.000 claims abstract description 23
- 206010060820 Joint injury Diseases 0.000 claims abstract description 20
- 241000124008 Mammalia Species 0.000 claims abstract description 18
- -1 (1R, 2S, 3R, 4S) -3- (3- (4-chlorophenyl) -1,2,4-oxadiazol-5-yl) -7-oxabicyclo [2.2.1] heptane-2 carboxamido Chemical group 0.000 claims description 217
- 125000000217 alkyl group Chemical group 0.000 claims description 171
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 121
- 125000001424 substituent group Chemical group 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 90
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 84
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical class 0.000 claims description 77
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 64
- 125000001072 heteroaryl group Chemical group 0.000 claims description 64
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 60
- 239000012634 fragment Substances 0.000 claims description 58
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 53
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 46
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 38
- 210000004027 cell Anatomy 0.000 claims description 37
- 125000002619 bicyclic group Chemical group 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 206010003246 arthritis Diseases 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 239000004305 biphenyl Substances 0.000 claims description 23
- 125000004429 atom Chemical group 0.000 claims description 21
- 210000000845 cartilage Anatomy 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 201000008482 osteoarthritis Diseases 0.000 claims description 18
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 16
- DEOUZFWSQWEPGE-UHFFFAOYSA-N 2-methylheptanamide Chemical compound CCCCCC(C)C(N)=O DEOUZFWSQWEPGE-UHFFFAOYSA-N 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 230000004936 stimulating effect Effects 0.000 claims description 16
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 15
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- SDCTXBJSIRBULY-UHFFFAOYSA-N 2-methylhept-2-enamide Chemical compound CCCCC=C(C)C(N)=O SDCTXBJSIRBULY-UHFFFAOYSA-N 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 206010048873 Traumatic arthritis Diseases 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- OVKXDANNQWXYKF-UHFFFAOYSA-N 2-methyloctanamide Chemical compound CCCCCCC(C)C(N)=O OVKXDANNQWXYKF-UHFFFAOYSA-N 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- JBBWIOOUTUWSMJ-FSDCSDTHSA-N (1R,2R,3S,4S)-3-(2-aminopyridin-4-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC1=NC=CC(=C1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl JBBWIOOUTUWSMJ-FSDCSDTHSA-N 0.000 claims description 4
- RSVHECROVCKUGC-YVSFHVDLSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-[2-(dimethylamino)pyrimidin-5-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C=1C=NC(=NC1)N(C)C)O2 RSVHECROVCKUGC-YVSFHVDLSA-N 0.000 claims description 4
- HNLJEOAFXYIQQM-YVSFHVDLSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-YVSFHVDLSA-N 0.000 claims description 4
- HNLJEOAFXYIQQM-YYIAUSFCSA-N (1S,2S,3R,4R)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@@H]1[C@@H]2CC[C@H]([C@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-YYIAUSFCSA-N 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 206010071155 Autoimmune arthritis Diseases 0.000 claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
- RUJMSTTXGZTEFM-YLFCFFPRSA-N (1R,2S,3R,4S)-N-(4-chloro-3-fluorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=C(C=C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)F RUJMSTTXGZTEFM-YLFCFFPRSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- KPLOPVKRBXYRPR-BQJUDKOJSA-N (1R,2R,3R,4S)-3-(3-chloro-2-fluoropyridin-4-yl)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C(=NC=CC1[C@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)C2=C(C=CC=C2)F)F)F KPLOPVKRBXYRPR-BQJUDKOJSA-N 0.000 claims description 2
- QXWURMRTXWCESK-ZWQIFLOQSA-N (1R,2R,3R,4S)-3-cyano-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(#N)[C@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)C2=C(C=CC=C2)F)F QXWURMRTXWCESK-ZWQIFLOQSA-N 0.000 claims description 2
- HNLJEOAFXYIQQM-HZMVEIRTSA-N (1R,2R,3R,4S)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-HZMVEIRTSA-N 0.000 claims description 2
- RUJMSTTXGZTEFM-HZMVEIRTSA-N (1R,2R,3R,4S)-N-(4-chloro-3-fluorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=C(C=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)F RUJMSTTXGZTEFM-HZMVEIRTSA-N 0.000 claims description 2
- VOBYFPMODSAXHI-KPHFQPKLSA-N (1R,2R,3R,4S)-N-[2-fluoro-3-(trifluoromethyl)phenyl]-3-[(2R)-6-(trifluoromethyl)piperidin-2-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC=C1C(F)(F)F)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1[C@@H]1NC(CCC1)C(F)(F)F)O2 VOBYFPMODSAXHI-KPHFQPKLSA-N 0.000 claims description 2
- OZXSVCPNECNUNQ-QUMGSSFMSA-N (1R,2R,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-(2-methylindazol-5-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC(=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1C1=CC3=CN(N=C3C=C1)C)O2)C2=C(C=CC=C2)F OZXSVCPNECNUNQ-QUMGSSFMSA-N 0.000 claims description 2
- RZKJGFLWJHMPRP-FSDCSDTHSA-N (1R,2R,3S,4S)-3-(2-chloropyridin-4-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=NC=CC(=C1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl RZKJGFLWJHMPRP-FSDCSDTHSA-N 0.000 claims description 2
- JUOLPQPINGHKQE-MHORFTMASA-N (1R,2R,3S,4S)-3-(2-cyanopyridin-4-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(#N)C1=NC=CC(=C1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl JUOLPQPINGHKQE-MHORFTMASA-N 0.000 claims description 2
- BNJVNFLIRFNJLF-NBMJBFSESA-N (1R,2R,3S,4S)-3-(6-acetamidopyridin-3-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(C)(=O)NC1=CC=C(C=N1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl BNJVNFLIRFNJLF-NBMJBFSESA-N 0.000 claims description 2
- AUBKTPZIYBUQEK-FSDCSDTHSA-N (1R,2R,3S,4S)-3-(6-aminopyridin-3-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC1=CC=C(C=N1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl AUBKTPZIYBUQEK-FSDCSDTHSA-N 0.000 claims description 2
- WHDIWQYRADUTJD-YVSFHVDLSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C=1CCNCC1)O2 WHDIWQYRADUTJD-YVSFHVDLSA-N 0.000 claims description 2
- WPOALLSIKAOFQJ-XGUBFFRZSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-(1H-pyrazol-4-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C=1C=NNC1)O2 WPOALLSIKAOFQJ-XGUBFFRZSA-N 0.000 claims description 2
- QQSYRHRAPSZWPV-NBMJBFSESA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-[2-(ethylsulfonylamino)pyridin-4-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC(=NC=C1)NS(=O)(=O)CC)O2 QQSYRHRAPSZWPV-NBMJBFSESA-N 0.000 claims description 2
- VNWLFRNEPGTWGX-JSJNYSNDSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-[2-(propanoylamino)pyridin-4-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC(=NC=C1)NC(CC)=O)O2 VNWLFRNEPGTWGX-JSJNYSNDSA-N 0.000 claims description 2
- SYKWPWSROSZFSK-WKZKVMAPSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-[2-[di(propanoyl)amino]pyridin-4-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC(=NC=C1)N(C(CC)=O)C(CC)=O)O2 SYKWPWSROSZFSK-WKZKVMAPSA-N 0.000 claims description 2
- NDBXTTIPHAMYPH-MQFRRQCYSA-N (1R,2R,3S,4S)-N-(3-chloro-4-phenylphenyl)-3-[6-(trifluoromethyl)pyridin-2-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=CC(=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=NC(=CC=C1)C(F)(F)F)O2)C2=CC=CC=C2 NDBXTTIPHAMYPH-MQFRRQCYSA-N 0.000 claims description 2
- SZUMGMNVGATLER-BJESRGMDSA-N (1R,2R,3S,4S)-N-(4-phenylphenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1(=CC=C(C=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC=NC=C1)O2)C2=CC=CC=C2 SZUMGMNVGATLER-BJESRGMDSA-N 0.000 claims description 2
- PMKYMQNCNVMDEK-MQFRRQCYSA-N (1R,2R,3S,4S)-N-[3-chloro-4-(2-fluorophenyl)phenyl]-3-[6-(trifluoromethyl)pyridin-2-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=CC(=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=NC(=CC=C1)C(F)(F)F)O2)C2=C(C=CC=C2)F PMKYMQNCNVMDEK-MQFRRQCYSA-N 0.000 claims description 2
- PAIQAKBTYYBSKX-SJXGUFTOSA-N (1R,2S,3R,4S)-N-(3,4-dichlorophenyl)-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC(=NN1C)C(F)(F)F)O2 PAIQAKBTYYBSKX-SJXGUFTOSA-N 0.000 claims description 2
- IMDAQWXKAOBUTA-ZJIFWQFVSA-N (1R,2S,3R,4S)-N-(3-chloro-2-fluorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C(=C(C=CC1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)F IMDAQWXKAOBUTA-ZJIFWQFVSA-N 0.000 claims description 2
- ROKVOUUZKUEBKF-WBADGQHESA-N (1R,2S,3R,4S)-N-(3-chloro-4-phenylphenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=CC(=C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)C2=CC=CC=C2 ROKVOUUZKUEBKF-WBADGQHESA-N 0.000 claims description 2
- FLWIAHAGHQVMBD-BSDSXHPESA-N (1R,2S,3R,4S)-N-(4-cyanophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 FLWIAHAGHQVMBD-BSDSXHPESA-N 0.000 claims description 2
- FDRZFNZLUYEGRG-WBADGQHESA-N (1R,2S,3R,4S)-N-[4-(2,4-difluorophenyl)-3-fluorophenyl]-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound N1=CC=C(C=C1)[C@H]1[C@@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)C2=C(C=C(C=C2)F)F)F FDRZFNZLUYEGRG-WBADGQHESA-N 0.000 claims description 2
- QXWURMRTXWCESK-DQEVTTJGSA-N (1S,2R,3R,4R)-3-cyano-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(#N)[C@H]1[C@H]([C@@H]2CC[C@H]1O2)C(=O)NC2=CC(=C(C=C2)C2=C(C=CC=C2)F)F QXWURMRTXWCESK-DQEVTTJGSA-N 0.000 claims description 2
- BDLPESNKYNGDQC-JONQDZQNSA-N (1S,2R,3R,4S)-N-(3,4-dichlorophenyl)-3-pyrazin-2-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@@H]2CC[C@@H]([C@H]1C1=NC=CN=C1)O2 BDLPESNKYNGDQC-JONQDZQNSA-N 0.000 claims description 2
- ZMSTUJPMLPIMKA-MWDXBVQZSA-N (1S,2S,3R,4S)-N-(1-methylsulfonylpiperidin-4-yl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound CS(=O)(=O)N1CCC(CC1)NC(=O)[C@@H]1[C@@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 ZMSTUJPMLPIMKA-MWDXBVQZSA-N 0.000 claims description 2
- KODIOVHGSTVKJH-CLAROIROSA-N (1S,2S,3S,4R)-3-(1-methylpyrazol-3-yl)-N-(4-phenylphenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1(=CC=C(C=C1)NC(=O)[C@@H]1[C@@H]2CC[C@H]([C@@H]1C1=NN(C=C1)C)O2)C2=CC=CC=C2 KODIOVHGSTVKJH-CLAROIROSA-N 0.000 claims description 2
- JASIXZBMIRNRJJ-WZYRSQIMSA-N (1S,2S,3S,4R)-N-(4-phenylphenyl)-3-pyridin-3-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1(=CC=C(C=C1)NC(=O)[C@@H]1[C@@H]2CC[C@H]([C@@H]1C=1C=NC=CC1)O2)C2=CC=CC=C2 JASIXZBMIRNRJJ-WZYRSQIMSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- DWVSVHKBLSVJFW-UHFFFAOYSA-N 3-oxatricyclo[3.2.1.02,4]octane-2-carboxamide Chemical compound C12C3(OC3C(CC1)C2)C(=O)N DWVSVHKBLSVJFW-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
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- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1346—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells
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| PCT/US2015/030303 WO2015175487A1 (en) | 2014-05-13 | 2015-05-12 | Compounds and compositions for inducing chondrogenesis |
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| WO2014151953A1 (en) | 2013-03-15 | 2014-09-25 | The California Institute For Biomedical Research | Compounds and methods for inducing chondrogenesis |
| UY36118A (es) * | 2014-05-13 | 2016-01-08 | Novartis Ag | Compuestos y composiciones para inducir condrogénesis |
| IL266361B2 (en) * | 2016-11-14 | 2024-02-01 | Novartis Ag | Methods and preparations for the treatment of cartilage damage and arthritis |
| CN110809468A (zh) * | 2017-04-24 | 2020-02-18 | 斯克利普斯研究所 | 诱导软骨发生的方法 |
| JOP20190282A1 (ar) * | 2017-06-09 | 2019-12-05 | Novartis Ag | مركبات وتركيبات لحث تكوّن الغضاريف |
| ES2981903T3 (es) * | 2017-11-10 | 2024-10-14 | Novartis Ag | Formulaciones de liberación prolongada para aplicaciones intraarticulares |
| CN112424207B (zh) | 2018-07-25 | 2024-03-19 | 诺华股份有限公司 | Nlrp3炎性小体抑制剂 |
| US12365692B2 (en) * | 2018-12-06 | 2025-07-22 | Novartis Ag | 6-hydroxy-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide derivatives for inducing chondrogenesis for treating joint damage |
| WO2020115683A1 (en) | 2018-12-06 | 2020-06-11 | Novartis Ag | 5-hydroxy-7-oxabicyclo[2.2.1]heptane-2-carboxamide derivatives for inducing chondrogenesis for treating joint damage |
| CN111601789A (zh) * | 2018-12-20 | 2020-08-28 | 江苏凯迪恩医药科技有限公司 | 一种含氮杂环化合物、其制备方法及应用 |
| UY38687A (es) | 2019-05-17 | 2023-05-15 | Novartis Ag | Inhibidores del inflamasoma nlrp3, composiciones, combinaciones de los mismos y métodos para su uso |
| RU2733472C1 (ru) * | 2020-02-26 | 2020-10-01 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | N-Ацилгидразон фенхона с фрагментом эпоксиизоиндола, используемый в качестве ингибитора репродукции вируса Хантаан |
| CN114763347B (zh) * | 2021-01-15 | 2024-06-21 | 华东师范大学 | 一类用于诱导间充质干细胞向软骨分化的化合物及其应用 |
| UY40374A (es) | 2022-08-03 | 2024-02-15 | Novartis Ag | Inhibidores de inflamasoma nlrp3 |
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