JP2017519729A5 - - Google Patents
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- Publication number
- JP2017519729A5 JP2017519729A5 JP2016567425A JP2016567425A JP2017519729A5 JP 2017519729 A5 JP2017519729 A5 JP 2017519729A5 JP 2016567425 A JP2016567425 A JP 2016567425A JP 2016567425 A JP2016567425 A JP 2016567425A JP 2017519729 A5 JP2017519729 A5 JP 2017519729A5
- Authority
- JP
- Japan
- Prior art keywords
- carboxamide
- oxabicyclo
- heptane
- pyridin
- biphenyl
- 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.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims description 86
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000001475 halogen functional group Chemical group 0.000 claims description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 25
- 125000002619 bicyclic group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 8
- 102100025668 Angiopoietin-related protein 3 Human genes 0.000 claims description 8
- 101710085848 Angiopoietin-related protein 3 Proteins 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 150000003431 steroids Chemical class 0.000 claims description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 102100035323 Fibroblast growth factor 18 Human genes 0.000 claims description 4
- 244000068988 Glycine max Species 0.000 claims description 4
- 235000010469 Glycine max Nutrition 0.000 claims description 4
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims description 4
- 101000878128 Homo sapiens Fibroblast growth factor 18 Proteins 0.000 claims description 4
- 244000025272 Persea americana Species 0.000 claims description 4
- 235000008673 Persea americana Nutrition 0.000 claims description 4
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 4
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 108010068072 salmon calcitonin Proteins 0.000 claims description 4
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 4
- 206010060820 Joint injury Diseases 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 210000001612 chondrocyte Anatomy 0.000 claims description 3
- 230000004069 differentiation Effects 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 206010071155 Autoimmune arthritis Diseases 0.000 claims description 2
- 206010048873 Traumatic arthritis Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- -1 salts compound Chemical class 0.000 claims 52
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 17
- DEOUZFWSQWEPGE-UHFFFAOYSA-N 2-methylheptanamide Chemical compound CCCCCC(C)C(N)=O DEOUZFWSQWEPGE-UHFFFAOYSA-N 0.000 claims 13
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 12
- SDCTXBJSIRBULY-UHFFFAOYSA-N 2-methylhept-2-enamide Chemical compound CCCCC=C(C)C(N)=O SDCTXBJSIRBULY-UHFFFAOYSA-N 0.000 claims 9
- 150000003857 carboxamides Chemical class 0.000 claims 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 7
- 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 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 2
- 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 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims 2
- 235000001968 nicotinic acid Nutrition 0.000 claims 2
- 239000011664 nicotinic acid Substances 0.000 claims 2
- 235000005282 vitamin D3 Nutrition 0.000 claims 2
- 239000011647 vitamin D3 Substances 0.000 claims 2
- 229940021056 vitamin d3 Drugs 0.000 claims 2
- RILLDHZUDOPEKX-CSGUBPAMSA-N (1R,2R,3R,4S)-3-(2,6-dichloropyridin-4-yl)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-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)C2=C(C=CC=C2)F)F)Cl RILLDHZUDOPEKX-CSGUBPAMSA-N 0.000 claims 1
- OBOVUOOHRHRXJM-JVSAHFFESA-N (1R,2R,3R,4S)-3-(2-aminopyridin-4-yl)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-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)C2=C(C=CC=C2)F)F OBOVUOOHRHRXJM-JVSAHFFESA-N 0.000 claims 1
- SAMYBFPISJORKJ-KEZOAJOQSA-N (1R,2R,3R,4S)-3-(2-cyanopyridin-4-yl)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-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)C2=C(C=CC=C2)F)F SAMYBFPISJORKJ-KEZOAJOQSA-N 0.000 claims 1
- 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 1
- RPNNJQWXRWPWPK-AFXVXQJMSA-N (1R,2R,3R,4S)-3-[2-(dimethylamino)pyrimidin-5-yl]-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-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]1C=1C=NC(=NC1)N(C)C)O2)C2=C(C=CC=C2)F RPNNJQWXRWPWPK-AFXVXQJMSA-N 0.000 claims 1
- 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 1
- FUGGGSUUMHGZBG-ABFRBSLYSA-N (1R,2R,3R,4S)-N-(3,4-dichlorophenyl)-3-[6-(trifluoromethyl)pyridin-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(=CC=C1)C(F)(F)F)O2 FUGGGSUUMHGZBG-ABFRBSLYSA-N 0.000 claims 1
- 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 1
- NWLYGROCUIDOIK-PSBKLILYSA-N (1R,2R,3R,4S)-N-(3-chloro-4-phenylphenyl)-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-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(=NN1C)C(F)(F)F)O2)C2=CC=CC=C2 NWLYGROCUIDOIK-PSBKLILYSA-N 0.000 claims 1
- 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 1
- SZUMGMNVGATLER-AFXVXQJMSA-N (1R,2R,3R,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-AFXVXQJMSA-N 0.000 claims 1
- VCYAZXUKSYKWPV-XNISGKROSA-N (1R,2R,3R,4S)-N-(5-chloropyridin-2-yl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=CC(=NC1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 VCYAZXUKSYKWPV-XNISGKROSA-N 0.000 claims 1
- XMJYLRLPAJIJFH-ABFRBSLYSA-N (1R,2R,3R,4S)-N-[2-fluoro-3-(trifluoromethoxy)phenyl]-3-(4-methylpyridin-2-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC=C1OC(F)(F)F)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@H]1C1=NC=CC(=C1)C)O2 XMJYLRLPAJIJFH-ABFRBSLYSA-N 0.000 claims 1
- 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 1
- DGEKGDKWPJXAQV-MXYBEHONSA-N (1R,2R,3R,4S)-N-[2-fluoro-3-(trifluoromethyl)phenyl]-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-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]1C1=CC(=NN1C)C(F)(F)F)O2 DGEKGDKWPJXAQV-MXYBEHONSA-N 0.000 claims 1
- NEZXZCSANMAKHG-YJNKXOJESA-N (1R,2R,3R,4S)-N-[2-fluoro-3-(trifluoromethyl)phenyl]-3-pyrazin-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]1C1=NC=CN=C1)O2 NEZXZCSANMAKHG-YJNKXOJESA-N 0.000 claims 1
- CXQJLMSKDPJIPA-NLJWQWLVSA-N (1R,2R,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-1,4-dimethyl-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC(=C1)NC(=O)[C@H]1[C@]2(CC[C@@]([C@H]1C1=CC=NC=C1)(O2)C)C)C2=C(C=CC=C2)F CXQJLMSKDPJIPA-NLJWQWLVSA-N 0.000 claims 1
- 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 1
- NGLXTRZPFFJNHF-KEZOAJOQSA-N (1R,2R,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-(4-methylpyridin-2-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=NC=CC(=C1)C)O2)C2=C(C=CC=C2)F NGLXTRZPFFJNHF-KEZOAJOQSA-N 0.000 claims 1
- BJJLVUWODRHRMY-PSBKLILYSA-N (1R,2R,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-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=CC(=NN1C)C(F)(F)F)O2)C2=C(C=CC=C2)F BJJLVUWODRHRMY-PSBKLILYSA-N 0.000 claims 1
- WOMWHEPQPATOAL-JVSAHFFESA-N (1R,2R,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-[6-(trifluoromethyl)pyridin-2-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=NC(=CC=C1)C(F)(F)F)O2)C2=C(C=CC=C2)F WOMWHEPQPATOAL-JVSAHFFESA-N 0.000 claims 1
- OBOVUOOHRHRXJM-MQFRRQCYSA-N (1R,2R,3S,4S)-3-(2-aminopyridin-4-yl)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-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)C2=C(C=CC=C2)F)F OBOVUOOHRHRXJM-MQFRRQCYSA-N 0.000 claims 1
- FUWRNBVXOZNPHN-XGUBFFRZSA-N (1R,2R,3S,4S)-3-(2-aminopyrimidin-5-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC1=NC=C(C=N1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl FUWRNBVXOZNPHN-XGUBFFRZSA-N 0.000 claims 1
- 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 1
- 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 1
- UMMQZCGSYBINEJ-MHORFTMASA-N (1R,2R,3S,4S)-3-(4-carbamoylphenyl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(N)(=O)C1=CC=C(C=C1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl UMMQZCGSYBINEJ-MHORFTMASA-N 0.000 claims 1
- WDBAVCVZUZDHNI-YVSFHVDLSA-N (1R,2R,3S,4S)-3-(5-aminopyridin-3-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC=1C=C(C=NC1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl WDBAVCVZUZDHNI-YVSFHVDLSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- KYNKJEVYTRHSEJ-MHORFTMASA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-(2-methylpyridin-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)C)O2 KYNKJEVYTRHSEJ-MHORFTMASA-N 0.000 claims 1
- DDIKLEUGLHMXHE-YVSFHVDLSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-(3,6-dihydro-2H-pyran-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=1CCOCC1)O2 DDIKLEUGLHMXHE-YVSFHVDLSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- FUGGGSUUMHGZBG-FSDCSDTHSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-[6-(trifluoromethyl)pyridin-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(=CC=C1)C(F)(F)F)O2 FUGGGSUUMHGZBG-FSDCSDTHSA-N 0.000 claims 1
- 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 1
- RNUVCPSPSMCUFS-FZKCQIBNSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-pyrimidin-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=NC=NC=C1)O2 RNUVCPSPSMCUFS-FZKCQIBNSA-N 0.000 claims 1
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- JASIXZBMIRNRJJ-BJESRGMDSA-N (1R,2R,3S,4S)-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-BJESRGMDSA-N 0.000 claims 1
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- WOMWHEPQPATOAL-MQFRRQCYSA-N (1R,2R,3S,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-[6-(trifluoromethyl)pyridin-2-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=NC(=CC=C1)C(F)(F)F)O2)C2=C(C=CC=C2)F WOMWHEPQPATOAL-MQFRRQCYSA-N 0.000 claims 1
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- OZUNIYHQPFHHHH-BJESRGMDSA-N (1R,2R,3S,4S)-N-[4-(2-chlorophenyl)-3-fluorophenyl]-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=C(C=C(C=C1)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC=NC=C1)O2)F OZUNIYHQPFHHHH-BJESRGMDSA-N 0.000 claims 1
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- KJNHKYLBKZMSPT-WREZULKGSA-N (1R,2R,4S,5S)-N-[3-chloro-4-(2-fluorophenyl)phenyl]-4-pyridin-4-yl-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide Chemical compound ClC1=C(C=CC(=C1)NC(=O)[C@]12[C@H]3CC[C@@H]([C@@]2(C1)C1=CC=NC=C1)O3)C3=C(C=CC=C3)F KJNHKYLBKZMSPT-WREZULKGSA-N 0.000 claims 1
- JCYXMWKTKSNTRF-WREZULKGSA-N (1R,2R,4S,5S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-4-pyridin-4-yl-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide Chemical compound FC1=C(C=CC(=C1)NC(=O)[C@]12[C@H]3CC[C@@H]([C@@]2(C1)C1=CC=NC=C1)O3)C3=C(C=CC=C3)F JCYXMWKTKSNTRF-WREZULKGSA-N 0.000 claims 1
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- HNLJEOAFXYIQQM-YLFCFFPRSA-N (1R,2S,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-YLFCFFPRSA-N 0.000 claims 1
- DQXMCYMFNXUVLN-BSDSXHPESA-N (1R,2S,3R,4S)-N-(4-chloro-2-cyanophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=CC(=C(C=C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)C#N DQXMCYMFNXUVLN-BSDSXHPESA-N 0.000 claims 1
- IXGBBZRJLYOPBY-SJXGUFTOSA-N (1R,2S,3R,4S)-N-(4-chloropyridin-2-yl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC1=CC(=NC=C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 IXGBBZRJLYOPBY-SJXGUFTOSA-N 0.000 claims 1
- 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 1
- KIHFNBUZIVCFRX-YLFCFFPRSA-N (1R,2S,3R,4S)-N-(5-chloro-2-fluorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=CC(=C(C1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)F KIHFNBUZIVCFRX-YLFCFFPRSA-N 0.000 claims 1
- KJRMJUGCXQWJCG-XOSAIJSUSA-N (1R,2S,3R,4S)-N-(5-chloro-4-methylpyridin-2-yl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C(=CC(=NC1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2)C KJRMJUGCXQWJCG-XOSAIJSUSA-N 0.000 claims 1
- XMJYLRLPAJIJFH-XOSAIJSUSA-N (1R,2S,3R,4S)-N-[2-fluoro-3-(trifluoromethoxy)phenyl]-3-(4-methylpyridin-2-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC=C1OC(F)(F)F)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=NC=CC(=C1)C)O2 XMJYLRLPAJIJFH-XOSAIJSUSA-N 0.000 claims 1
- NGVUSLBMZDNYEJ-SJXGUFTOSA-N (1R,2S,3R,4S)-N-[2-fluoro-3-(trifluoromethoxy)phenyl]-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=C(C=CC=C1OC(F)(F)F)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 NGVUSLBMZDNYEJ-SJXGUFTOSA-N 0.000 claims 1
- NGLXTRZPFFJNHF-OLKYXYMISA-N (1R,2S,3R,4S)-N-[3-fluoro-4-(2-fluorophenyl)phenyl]-3-(4-methylpyridin-2-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=NC=CC(=C1)C)O2)C2=C(C=CC=C2)F NGLXTRZPFFJNHF-OLKYXYMISA-N 0.000 claims 1
- BKRCVLBEXYBVIW-YLFCFFPRSA-N (1R,2S,3R,4S)-N-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC=1C=C(C=CC1OC(F)(F)F)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 BKRCVLBEXYBVIW-YLFCFFPRSA-N 0.000 claims 1
- 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 1
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- MEBDEENOPNHQIG-YLFCFFPRSA-N (1R,2S,3R,4S)-N-cyclohexyl-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1(CCCCC1)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC=NC=C1)O2 MEBDEENOPNHQIG-YLFCFFPRSA-N 0.000 claims 1
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- MUOZTEXGEGMYFG-ZEQRLZLVSA-N (1S,4S)-N-(3-chloro-4-phenylphenyl)-3-[2-(oxan-4-yl)pyrazol-3-yl]-7-oxabicyclo[2.2.1]hept-2-ene-2-carboxamide Chemical compound ClC1=C(C=CC(=C1)NC(=O)C=1[C@@H]2CC[C@@H](C1C1=CC=NN1C1CCOCC1)O2)C2=CC=CC=C2 MUOZTEXGEGMYFG-ZEQRLZLVSA-N 0.000 claims 1
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
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- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
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| 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 |
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