TW201713621A - 經取代之吡啶及其使用方法 - Google Patents
經取代之吡啶及其使用方法 Download PDFInfo
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- TW201713621A TW201713621A TW105117470A TW105117470A TW201713621A TW 201713621 A TW201713621 A TW 201713621A TW 105117470 A TW105117470 A TW 105117470A TW 105117470 A TW105117470 A TW 105117470A TW 201713621 A TW201713621 A TW 201713621A
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- TW
- Taiwan
- Prior art keywords
- amino
- sulfonyl
- pyridine
- phenyl
- carboxamide
- Prior art date
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- 238000000034 method Methods 0.000 title abstract description 56
- 150000003222 pyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 320
- 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 116
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 36
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 181
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 171
- -1 hexahydropyridyl Chemical group 0.000 claims description 170
- 125000000217 alkyl group Chemical group 0.000 claims description 159
- 229910052731 fluorine Inorganic materials 0.000 claims description 148
- 125000005843 halogen group Chemical group 0.000 claims description 135
- 235000019000 fluorine Nutrition 0.000 claims description 132
- 229910052757 nitrogen Inorganic materials 0.000 claims description 130
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 112
- 125000000623 heterocyclic group Chemical group 0.000 claims description 108
- 125000001153 fluoro group Chemical group F* 0.000 claims description 105
- 125000002950 monocyclic group Chemical group 0.000 claims description 96
- 239000011737 fluorine Substances 0.000 claims description 93
- 229910052717 sulfur Inorganic materials 0.000 claims description 93
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 91
- 150000003839 salts Chemical class 0.000 claims description 90
- 229910052760 oxygen Inorganic materials 0.000 claims description 85
- 125000001424 substituent group Chemical group 0.000 claims description 70
- 239000003814 drug Substances 0.000 claims description 60
- 125000005842 heteroatom Chemical group 0.000 claims description 60
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 49
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 47
- 229940124597 therapeutic agent Drugs 0.000 claims description 37
- 239000003795 chemical substances by application Substances 0.000 claims description 36
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 33
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 26
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 238000006467 substitution reaction Methods 0.000 claims description 21
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 14
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 11
- 125000002393 azetidinyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 10
- 125000003566 oxetanyl group Chemical group 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 230000003321 amplification Effects 0.000 claims description 6
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- WNAMNXHPDLFKCW-JTQLQIEISA-N 3-amino-6-(4-fluorophenyl)-5-(2-hydroxyethylsulfonyl)-N-[(2S)-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC(=C(C=1)S(=O)(=O)CCO)C1=CC=C(C=C1)F)C(=O)NC[C@H](C)O WNAMNXHPDLFKCW-JTQLQIEISA-N 0.000 claims description 4
- FFAIBRXUCVJHIU-NSHDSACASA-N 3-amino-6-(4-fluorophenyl)-N-[(2S)-2-hydroxypropyl]-5-(2-methoxyethylsulfonyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC(=C(C=1)S(=O)(=O)CCOC)C1=CC=C(C=C1)F)C(=O)NC[C@H](C)O FFAIBRXUCVJHIU-NSHDSACASA-N 0.000 claims description 4
- BXLCENGNDVFRAZ-UHFFFAOYSA-N 3-hydroxyazetidine-1-carbaldehyde Chemical compound OC1CN(C=O)C1 BXLCENGNDVFRAZ-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- HPJZDAUEHSAWEB-GFCCVEGCSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NC[C@H](C(F)(F)F)O HPJZDAUEHSAWEB-GFCCVEGCSA-N 0.000 claims description 3
- LPCJNBWBKMLOOK-UHFFFAOYSA-N 3-amino-5-(benzenesulfonyl)-6-cyclopropyl-N-(2-hydroxyethyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC(=C(C=1)S(=O)(=O)C1=CC=CC=C1)C1CC1)C(=O)NCCO LPCJNBWBKMLOOK-UHFFFAOYSA-N 0.000 claims description 3
- GMCWWPFLRCXFKB-UHFFFAOYSA-N 3-amino-5-(benzenesulfonyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=CC=C1)C(=O)NCC(C(F)(F)F)O GMCWWPFLRCXFKB-UHFFFAOYSA-N 0.000 claims description 3
- ZOUVITOIQXPFHQ-JTQLQIEISA-N 3-amino-5-ethylsulfonyl-6-(4-fluorophenyl)-N-[(2S)-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC(=C(C=1)S(=O)(=O)CC)C1=CC=C(C=C1)F)C(=O)NC[C@H](C)O ZOUVITOIQXPFHQ-JTQLQIEISA-N 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- XDADNLHUFALPBV-UHFFFAOYSA-N [3-amino-5-(benzenesulfonyl)pyridin-2-yl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=CC=C1)C(=O)N1CC(C1)(C(F)(F)F)O XDADNLHUFALPBV-UHFFFAOYSA-N 0.000 claims description 3
- PDUMTJUIZPPPLP-UHFFFAOYSA-N [3-amino-5-[2-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=CC=C1)OC(F)(F)F)C(=O)N1CC(C1)(C(F)(F)F)O PDUMTJUIZPPPLP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- SUDKICROUMHBPV-UHFFFAOYSA-N 1-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carbonyl]-N,N-dimethylazetidine-3-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)C(=O)N(C)C SUDKICROUMHBPV-UHFFFAOYSA-N 0.000 claims description 2
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 2
- BCBVQAPXIZMHCU-UHFFFAOYSA-N 3-amino-5-(2,3-dihydro-1,4-benzoxazin-4-ylsulfonyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CCOC2=C1C=CC=C2)C(=O)NCC(C(F)(F)F)O BCBVQAPXIZMHCU-UHFFFAOYSA-N 0.000 claims description 2
- FZJSJYFWYIPIKS-UHFFFAOYSA-N 3-amino-5-(3,3-difluoropyrrolidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CC(CC1)(F)F)C(=O)NCC(C(F)(F)F)O FZJSJYFWYIPIKS-UHFFFAOYSA-N 0.000 claims description 2
- IRWJIESVAQQVTG-UHFFFAOYSA-N 3-amino-5-(3,3-dimethylazetidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CC(C1)(C)C)C(=O)NCC(C(F)(F)F)O IRWJIESVAQQVTG-UHFFFAOYSA-N 0.000 claims description 2
- UIGDHBJBRFGZNX-UHFFFAOYSA-N 3-amino-5-(3-fluorophenyl)sulfonyl-N-(2-hydroxy-2-methylpropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC(=CC=C1)F)C(=O)NCC(C)(C)O UIGDHBJBRFGZNX-UHFFFAOYSA-N 0.000 claims description 2
- NRMAOHMDPQNWHA-UHFFFAOYSA-N 3-amino-5-(3-fluoropiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CC(CCC1)F)C(=O)NCC(C(F)(F)F)O NRMAOHMDPQNWHA-UHFFFAOYSA-N 0.000 claims description 2
- ZYTUSLWLOMZNRO-UHFFFAOYSA-N 3-amino-5-(3-methylpiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CC(CCC1)C)C(=O)NCC(C(F)(F)F)O ZYTUSLWLOMZNRO-UHFFFAOYSA-N 0.000 claims description 2
- DAMDGCGBHYXPIN-UHFFFAOYSA-N 3-amino-5-(4,4-difluoropiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CCC(CC1)(F)F)C(=O)NCC(C(F)(F)F)O DAMDGCGBHYXPIN-UHFFFAOYSA-N 0.000 claims description 2
- XSZZEYRGUJNCAG-UHFFFAOYSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-(2-hydroxy-2-methylpropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NCC(C)(C)O XSZZEYRGUJNCAG-UHFFFAOYSA-N 0.000 claims description 2
- IITDENOGJSUHHE-UHFFFAOYSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxy-2-methylpropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NCC(C(F)(F)F)(C)O IITDENOGJSUHHE-UHFFFAOYSA-N 0.000 claims description 2
- YYCIYZHXBQHIHR-UHFFFAOYSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-(4,4,4-trifluoro-3-hydroxybutyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NCCC(C(F)(F)F)O YYCIYZHXBQHIHR-UHFFFAOYSA-N 0.000 claims description 2
- NAXPHBUQEPZMOO-UHFFFAOYSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-[(1-hydroxycyclopropyl)methyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NCC1(CC1)O NAXPHBUQEPZMOO-UHFFFAOYSA-N 0.000 claims description 2
- HPJZDAUEHSAWEB-LBPRGKRZSA-N 3-amino-5-(4-fluorophenyl)sulfonyl-N-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)NC[C@@H](C(F)(F)F)O HPJZDAUEHSAWEB-LBPRGKRZSA-N 0.000 claims description 2
- HVEHFAFPCHWBMN-UHFFFAOYSA-N 3-amino-5-(4-fluoropiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CCC(CC1)F)C(=O)NCC(C(F)(F)F)O HVEHFAFPCHWBMN-UHFFFAOYSA-N 0.000 claims description 2
- HCKNBBXZPJOPAX-UHFFFAOYSA-N 3-amino-5-(4-methoxyphenyl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC)C(=O)NCC(C(F)(F)F)O HCKNBBXZPJOPAX-UHFFFAOYSA-N 0.000 claims description 2
- HBLCKYQDJRPZDB-UHFFFAOYSA-N 3-amino-5-(4-methoxypiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CCC(CC1)OC)C(=O)NCC(C(F)(F)F)O HBLCKYQDJRPZDB-UHFFFAOYSA-N 0.000 claims description 2
- RTNNHXCBUKFIAY-UHFFFAOYSA-N 3-amino-5-(4-methylphenyl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)C)C(=O)NCC(C(F)(F)F)O RTNNHXCBUKFIAY-UHFFFAOYSA-N 0.000 claims description 2
- UHWZQSFHJLZORE-UHFFFAOYSA-N 3-amino-5-(4-methylpiperidin-1-yl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1CCC(CC1)C)C(=O)NCC(C(F)(F)F)O UHWZQSFHJLZORE-UHFFFAOYSA-N 0.000 claims description 2
- VGGNZRBONOBUCO-UHFFFAOYSA-N 3-amino-5-(4-propan-2-ylphenyl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)C(C)C)C(=O)NCC(C(F)(F)F)O VGGNZRBONOBUCO-UHFFFAOYSA-N 0.000 claims description 2
- BOZBBQFELBFTOV-UHFFFAOYSA-N 3-amino-5-(4-tert-butylphenyl)sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C(=O)NCC(C(F)(F)F)O BOZBBQFELBFTOV-UHFFFAOYSA-N 0.000 claims description 2
- YKUUVHSAJNAIMN-UHFFFAOYSA-N 3-amino-5-(oxolan-2-ylmethylsulfonyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)CC1OCCC1)C(=O)NCC(C(F)(F)F)O YKUUVHSAJNAIMN-UHFFFAOYSA-N 0.000 claims description 2
- UIOIXAQSHNKKBN-RZZZFEHKSA-N 3-amino-5-[(2R)-2-methylpyrrolidin-1-yl]sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1[C@@H](CCC1)C)C(=O)NCC(C(F)(F)F)O UIOIXAQSHNKKBN-RZZZFEHKSA-N 0.000 claims description 2
- UIOIXAQSHNKKBN-YMNIQAILSA-N 3-amino-5-[(2S)-2-methylpyrrolidin-1-yl]sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1[C@H](CCC1)C)C(=O)NCC(C(F)(F)F)O UIOIXAQSHNKKBN-YMNIQAILSA-N 0.000 claims description 2
- DGWZMXAZEBQJHS-BYDSUWOYSA-N 3-amino-5-[(3S)-3-fluoropyrrolidin-1-yl]sulfonyl-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1C[C@H](CC1)F)C(=O)NCC(C(F)(F)F)O DGWZMXAZEBQJHS-BYDSUWOYSA-N 0.000 claims description 2
- CSUHOXZSLFDKHJ-RGURZIINSA-N 3-amino-5-[2-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-N-[(2S)-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1C(CCC1)CO)C(=O)NC[C@H](C)O CSUHOXZSLFDKHJ-RGURZIINSA-N 0.000 claims description 2
- UPSNTELSQOJKHL-GFCCVEGCSA-N 3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonyl-N-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)NC[C@H](C(F)(F)F)O UPSNTELSQOJKHL-GFCCVEGCSA-N 0.000 claims description 2
- JQBOVGKRVFDOOS-UHFFFAOYSA-N 3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonyl-N-[2-hydroxy-3-(2-methylpropoxy)propyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)NCC(COCC(C)C)O JQBOVGKRVFDOOS-UHFFFAOYSA-N 0.000 claims description 2
- UIZPMUABDHMTPW-SNVBAGLBSA-N 3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonyl-N-[[(3R)-oxolan-3-yl]methyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)NC[C@@H]1COCC1 UIZPMUABDHMTPW-SNVBAGLBSA-N 0.000 claims description 2
- UIZPMUABDHMTPW-JTQLQIEISA-N 3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonyl-N-[[(3S)-oxolan-3-yl]methyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)NC[C@H]1COCC1 UIZPMUABDHMTPW-JTQLQIEISA-N 0.000 claims description 2
- UWCCWOYLZVSVHM-UHFFFAOYSA-N 3-amino-5-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-N-(2-hydroxy-3-propan-2-yloxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)C(=O)NCC(COC(C)C)O UWCCWOYLZVSVHM-UHFFFAOYSA-N 0.000 claims description 2
- MTWQKALFSZVBGR-UHFFFAOYSA-N 3-amino-5-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-N-(2-hydroxyethyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)C(=O)NCCO MTWQKALFSZVBGR-UHFFFAOYSA-N 0.000 claims description 2
- XKLDRUOEMRSYCZ-SNVBAGLBSA-N 3-amino-5-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-N-[(2R)-2-hydroxy-3-methoxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)C(=O)NC[C@H](COC)O XKLDRUOEMRSYCZ-SNVBAGLBSA-N 0.000 claims description 2
- RKQZTIZCDBARFG-UHFFFAOYSA-N 3-amino-5-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-N-[2-hydroxy-3-(2,2,2-trifluoroethoxy)propyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)C(=O)NCC(COCC(F)(F)F)O RKQZTIZCDBARFG-UHFFFAOYSA-N 0.000 claims description 2
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- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 1
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- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
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- IKVDXUFZJARKPF-UHFFFAOYSA-M zinc;cyclopropane;bromide Chemical compound Br[Zn+].C1C[CH-]1 IKVDXUFZJARKPF-UHFFFAOYSA-M 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- C07D491/02—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 two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562169881P | 2015-06-02 | 2015-06-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201713621A true TW201713621A (zh) | 2017-04-16 |
Family
ID=57440295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW105117470A TW201713621A (zh) | 2015-06-02 | 2016-06-02 | 經取代之吡啶及其使用方法 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US10047051B2 (OSRAM) |
| EP (1) | EP3303294A1 (OSRAM) |
| JP (1) | JP2018516932A (OSRAM) |
| KR (1) | KR20180029204A (OSRAM) |
| CN (1) | CN107922338A (OSRAM) |
| AR (1) | AR106865A1 (OSRAM) |
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| US20210401869A1 (en) * | 2015-02-20 | 2021-12-30 | Rosalind Franklin University Of Medicine And Science | Antisense Compounds Targeting Genes Associated with Cystic Fibrosis |
| US10138227B2 (en) * | 2016-06-03 | 2018-11-27 | Abbvie S.Á.R.L. | Heteroaryl substituted pyridines and methods of use |
| TW201811766A (zh) | 2016-08-29 | 2018-04-01 | 瑞士商諾華公司 | N-(吡啶-2-基)吡啶-磺醯胺衍生物及其用於疾病治療之用途 |
| US10399940B2 (en) | 2016-10-07 | 2019-09-03 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
| US9981910B2 (en) | 2016-10-07 | 2018-05-29 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
| US20200123137A1 (en) | 2016-12-20 | 2020-04-23 | AbbVie S.à.r.l. | Deuterated cftr modulators and methods of use |
| TW201831471A (zh) | 2017-02-24 | 2018-09-01 | 盧森堡商艾伯維公司 | 囊腫纖化症跨膜傳導調節蛋白的調節劑及其使用方法 |
| US10988454B2 (en) | 2017-09-14 | 2021-04-27 | Abbvie Overseas S.À.R.L. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| WO2019193062A1 (en) | 2018-04-03 | 2019-10-10 | Abbvie S.Á.R.L | Substituted pyrrolidines and their use |
| US20220127247A1 (en) * | 2019-02-06 | 2022-04-28 | Novartis Ag | N-(pyridin-2-yl)pyridine-sulfonamide derivatives and their use in the treatment of disease |
| US11345691B2 (en) | 2019-06-03 | 2022-05-31 | AbbVie Global Enterprises Ltd. | Prodrug modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| US11236067B2 (en) | 2019-07-12 | 2022-02-01 | Orphomed, Inc. | Compound for treating cystic fibrosis |
| WO2022150173A1 (en) | 2021-01-06 | 2022-07-14 | AbbVie Global Enterprises Ltd. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| US20220211692A1 (en) | 2021-01-06 | 2022-07-07 | AbbVie Global Enterprises Ltd. | Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of Use |
| IL309501A (en) | 2021-08-19 | 2024-02-01 | Syngenta Crop Protection Ag | Method for controlling pests resistant to diamide and compounds therefor |
| WO2023034946A1 (en) * | 2021-09-03 | 2023-03-09 | Genzyme Corporation | Indole compounds and uses thereof in the treatement of cystic fibrosis |
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| US7939558B2 (en) | 2004-06-04 | 2011-05-10 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof |
| US8354427B2 (en) | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
| HUE032540T2 (en) | 2004-06-24 | 2017-09-28 | Vertex Pharma | Modulators of ATP-binding cassette transporters |
| ES2548292T3 (es) | 2007-05-25 | 2015-10-15 | Vertex Pharmaceuticals Incorporated | Moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| PL2444120T3 (pl) | 2007-12-10 | 2018-02-28 | Novartis Ag | Spirocyklicze analogi amiloridu jako blokery ENac |
| CN101925603B (zh) | 2007-12-13 | 2013-12-04 | 沃泰克斯药物股份有限公司 | 囊性纤维化跨膜通道调节因子的调节剂 |
| NZ592504A (en) | 2008-10-23 | 2013-04-26 | Vertex Pharma | Solid forms of n-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide |
| US8367660B2 (en) | 2008-12-30 | 2013-02-05 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| US8247436B2 (en) * | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| ES2882807T3 (es) | 2011-09-16 | 2021-12-02 | Novartis Ag | Heterociclil carboxamidas N-sustituidas |
| ES2558457T3 (es) | 2011-09-16 | 2016-02-04 | Novartis Ag | Compuestos heterocíclicos para el tratamiento de fibrosis quística |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| AU2012312520A1 (en) | 2011-09-20 | 2014-05-08 | The University Of North Carolina At Chapel Hill | Regulation of sodium channels by PLUNC proteins |
| WO2014180562A1 (en) * | 2013-05-07 | 2014-11-13 | Galapagos Nv | Novel compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis |
| US9133210B2 (en) | 2013-08-08 | 2015-09-15 | Galapagos Nv | Compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis |
| CA2942386A1 (en) | 2014-03-13 | 2015-09-17 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| CA2942387A1 (en) | 2014-03-13 | 2015-09-17 | Proteostasis Therapeutics, Inc. | Compounds, compositions and methods of increasing cftr actvity |
| US20190154661A1 (en) * | 2016-05-09 | 2019-05-23 | Proteostasis Therapeutics, Inc. | Methods of identifying cftr modulators |
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2016
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- 2016-05-25 RU RU2017146661A patent/RU2017146661A/ru not_active Application Discontinuation
- 2016-05-25 CR CR20170595A patent/CR20170595A/es unknown
- 2016-05-25 CN CN201680043914.3A patent/CN107922338A/zh active Pending
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- 2016-05-25 KR KR1020177037457A patent/KR20180029204A/ko not_active Withdrawn
- 2016-05-25 EP EP16736610.3A patent/EP3303294A1/en not_active Withdrawn
- 2016-05-25 US US15/164,317 patent/US10047051B2/en active Active
- 2016-05-25 AU AU2016272702A patent/AU2016272702A1/en not_active Abandoned
- 2016-05-25 HK HK18112786.3A patent/HK1253581A1/zh unknown
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- 2016-06-02 AR ARP160101620A patent/AR106865A1/es unknown
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2017
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| JP2018516932A (ja) | 2018-06-28 |
| BR112017026132A2 (pt) | 2018-08-28 |
| RU2017146661A (ru) | 2019-07-15 |
| DOP2017000278A (es) | 2018-01-15 |
| US20160355480A1 (en) | 2016-12-08 |
| PE20180457A1 (es) | 2018-03-05 |
| PH12017502201A1 (en) | 2018-06-11 |
| ECSP17085494A (es) | 2019-03-29 |
| MX2017015591A (es) | 2018-04-30 |
| CL2017003067A1 (es) | 2018-06-01 |
| CR20170595A (es) | 2018-04-27 |
| CN107922338A (zh) | 2018-04-17 |
| CO2017012566A2 (es) | 2018-03-09 |
| EP3303294A1 (en) | 2018-04-11 |
| AR106865A1 (es) | 2018-02-28 |
| IL256032A (en) | 2018-01-31 |
| WO2016193812A1 (en) | 2016-12-08 |
| CA2988046A1 (en) | 2016-12-08 |
| KR20180029204A (ko) | 2018-03-20 |
| AU2016272702A1 (en) | 2017-12-21 |
| UY36702A (es) | 2016-12-30 |
| US10047051B2 (en) | 2018-08-14 |
| HK1253581A1 (zh) | 2019-06-21 |
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