KR20180029204A - 치환된 피리딘 및 사용 방법 - Google Patents
치환된 피리딘 및 사용 방법 Download PDFInfo
- Publication number
- KR20180029204A KR20180029204A KR1020177037457A KR20177037457A KR20180029204A KR 20180029204 A KR20180029204 A KR 20180029204A KR 1020177037457 A KR1020177037457 A KR 1020177037457A KR 20177037457 A KR20177037457 A KR 20177037457A KR 20180029204 A KR20180029204 A KR 20180029204A
- Authority
- KR
- South Korea
- Prior art keywords
- amino
- sulfonyl
- phenyl
- carboxamide
- pyridine
- 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- Withdrawn
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- 238000000034 method Methods 0.000 title claims abstract description 94
- 150000003222 pyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 325
- 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 116
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- -1 2 -cyclopropyl Chemical group 0.000 claims description 374
- 125000001153 fluoro group Chemical group F* 0.000 claims description 197
- 125000000217 alkyl group Chemical group 0.000 claims description 181
- 125000003545 alkoxy group Chemical group 0.000 claims description 179
- 125000005843 halogen group Chemical group 0.000 claims description 160
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 156
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 154
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 145
- 229910052757 nitrogen Inorganic materials 0.000 claims description 128
- 125000005842 heteroatom Chemical group 0.000 claims description 93
- 229910052760 oxygen Inorganic materials 0.000 claims description 93
- 229910052717 sulfur Inorganic materials 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 87
- CTBWWPIIRKWDDL-UHFFFAOYSA-N 3-amino-n,n-diethylbenzenesulfonamide Chemical compound CCN(CC)S(=O)(=O)C1=CC=CC(N)=C1 CTBWWPIIRKWDDL-UHFFFAOYSA-N 0.000 claims description 76
- 239000003814 drug Substances 0.000 claims description 65
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 64
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 59
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 58
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 229910052731 fluorine Inorganic materials 0.000 claims description 54
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 47
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 38
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 35
- 229940124597 therapeutic agent Drugs 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 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
- 125000002393 azetidinyl group Chemical group 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 235000007164 Oryza sativa Nutrition 0.000 claims description 20
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 20
- 235000009566 rice Nutrition 0.000 claims description 20
- 125000003386 piperidinyl group Chemical group 0.000 claims description 18
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 17
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 15
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 12
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003566 oxetanyl 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 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- INVJBYOXKDTRAB-UHFFFAOYSA-N 3,3-difluoroazetidine-1-carbaldehyde Chemical compound FC1(F)CN(C=O)C1 INVJBYOXKDTRAB-UHFFFAOYSA-N 0.000 claims description 4
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- NBJLTLGVBUBVLA-UHFFFAOYSA-N 1-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carbonyl]azetidine-3-carbonitrile 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#N NBJLTLGVBUBVLA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[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
- XILTWMLLALZONO-VIFPVBQESA-N 3-amino-5-[cyclobutyl(methyl)sulfamoyl]-N-[(2S)-2-hydroxypropyl]pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(N(C)C1CCC1)(=O)=O)C(=O)NC[C@H](C)O XILTWMLLALZONO-VIFPVBQESA-N 0.000 claims description 2
- VUECFWYLDITMCU-UHFFFAOYSA-N 3-amino-5-[cyclopropyl(2-methoxyethyl)sulfamoyl]-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(N(CCOC)C1CC1)(=O)=O)C(=O)NCC(C(F)(F)F)O VUECFWYLDITMCU-UHFFFAOYSA-N 0.000 claims description 2
- HDUZWBIERYJQSD-UHFFFAOYSA-N 3-amino-5-[cyclopropyl(methyl)sulfamoyl]-N-(3,3,3-trifluoro-2-hydroxypropyl)pyridine-2-carboxamide Chemical compound NC=1C(=NC=C(C=1)S(N(C)C1CC1)(=O)=O)C(=O)NCC(C(F)(F)F)O HDUZWBIERYJQSD-UHFFFAOYSA-N 0.000 claims description 2
- QBAFPUXVDIHRPD-UHFFFAOYSA-N 3-amino-N'-(2-hydroxyacetyl)-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carbohydrazide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)NNC(CO)=O QBAFPUXVDIHRPD-UHFFFAOYSA-N 0.000 claims description 2
- IQCYMBASMSUAKP-UHFFFAOYSA-N 3-amino-N'-(2-methoxyacetyl)-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carbohydrazide Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)NNC(COC)=O IQCYMBASMSUAKP-UHFFFAOYSA-N 0.000 claims description 2
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- LQXDPBBWNPNZCC-UHFFFAOYSA-N [3-amino-5-(3-fluorophenyl)sulfonylpyridin-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)F)C(=O)N1CC(C1)(C(F)(F)F)O LQXDPBBWNPNZCC-UHFFFAOYSA-N 0.000 claims description 2
- ZCHBGZYGDTWRDD-UHFFFAOYSA-N [3-amino-5-(4-fluorophenyl)sulfonylpyridin-2-yl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)F)C(=O)N1CC(C1)(C(F)(F)F)O ZCHBGZYGDTWRDD-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- BFJMRZZEASICIF-VIFPVBQESA-N [3-amino-5-[(2S)-2-methylpyrrolidin-1-yl]sulfonylpyridin-2-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)N1[C@H](CCC1)C)C(=O)N1CC(C1)O BFJMRZZEASICIF-VIFPVBQESA-N 0.000 claims description 2
- JAOBEDWSNMFKSH-UHFFFAOYSA-N [3-amino-5-[2-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3,3-difluoroazetidin-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)(F)F JAOBEDWSNMFKSH-UHFFFAOYSA-N 0.000 claims description 2
- LOTSMTAUTSQGJT-UHFFFAOYSA-N [3-amino-5-[2-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-hydroxyazetidin-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)O LOTSMTAUTSQGJT-UHFFFAOYSA-N 0.000 claims description 2
- RXPRJNXJDMYOQE-UHFFFAOYSA-N [3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3,3-dimethylazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)N1CC(C1)(C)C RXPRJNXJDMYOQE-UHFFFAOYSA-N 0.000 claims description 2
- AMFVXRKYHFEKMP-UHFFFAOYSA-N [3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)OC(F)(F)F)F)C(=O)N1CC(C1)O AMFVXRKYHFEKMP-UHFFFAOYSA-N 0.000 claims description 2
- LLVZTOOPOYYUGO-UHFFFAOYSA-N [3-amino-5-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonylpyridin-2-yl]-(3,3-dimethylazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)C(=O)N1CC(C1)(C)C LLVZTOOPOYYUGO-UHFFFAOYSA-N 0.000 claims description 2
- GIQTYQUBLIRQBU-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC2(COC2)C1 GIQTYQUBLIRQBU-UHFFFAOYSA-N 0.000 claims description 2
- QTAGZTFIFSKHRU-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3,3-difluoroazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)(F)F QTAGZTFIFSKHRU-UHFFFAOYSA-N 0.000 claims description 2
- OTPCPSZQNKTJTL-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3,3-difluoropyrrolidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(CC1)(F)F OTPCPSZQNKTJTL-UHFFFAOYSA-N 0.000 claims description 2
- KZKAXUGPEJBPKS-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3,3-dimethylazetidin-1-yl)methanone 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)C KZKAXUGPEJBPKS-UHFFFAOYSA-N 0.000 claims description 2
- YOSZXSLQQAARFX-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-cyclopropyl-3-hydroxyazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)(O)C1CC1 YOSZXSLQQAARFX-UHFFFAOYSA-N 0.000 claims description 2
- SUKBWPIPJJKQNG-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-ethyl-3-fluoroazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)(F)CC SUKBWPIPJJKQNG-UHFFFAOYSA-N 0.000 claims description 2
- YUKZQFUVNQVEKI-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-fluoroazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)F YUKZQFUVNQVEKI-UHFFFAOYSA-N 0.000 claims description 2
- HGCACXFIBVYVCN-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)O HGCACXFIBVYVCN-UHFFFAOYSA-N 0.000 claims description 2
- PSPNKTCMQOEXIF-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-hydroxypyrrolidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(CC1)O PSPNKTCMQOEXIF-UHFFFAOYSA-N 0.000 claims description 2
- YVHMLBFGBNPACU-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-methoxyazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)OC YVHMLBFGBNPACU-UHFFFAOYSA-N 0.000 claims description 2
- NBFVNHQZCJPOFJ-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-methylazetidin-1-yl)methanone 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 NBFVNHQZCJPOFJ-UHFFFAOYSA-N 0.000 claims description 2
- DRAVIGYHAYWPFZ-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(3-morpholin-4-ylazetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC(C1)N1CCOCC1 DRAVIGYHAYWPFZ-UHFFFAOYSA-N 0.000 claims description 2
- OMLFWZZCVXJEAS-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(6-oxa-2-azaspiro[3.4]octan-2-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC2(C1)COCC2 OMLFWZZCVXJEAS-UHFFFAOYSA-N 0.000 claims description 2
- BREHFWWRDWJRNC-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(6-oxa-2-azaspiro[3.5]nonan-2-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CC2(C1)COCCC2 BREHFWWRDWJRNC-UHFFFAOYSA-N 0.000 claims description 2
- MLEPOEJQYVNKAV-UHFFFAOYSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-(azetidin-1-yl)methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1CCC1 MLEPOEJQYVNKAV-UHFFFAOYSA-N 0.000 claims description 2
- LFCREYLRFWPTOE-SNVBAGLBSA-N [3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridin-2-yl]-[(3R)-3-fluoropyrrolidin-1-yl]methanone Chemical compound NC=1C(=NC=C(C=1)S(=O)(=O)C1=CC=C(C=C1)OC(F)(F)F)C(=O)N1C[C@@H](CC1)F LFCREYLRFWPTOE-SNVBAGLBSA-N 0.000 claims description 2
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- MDUSUFIKBUMDTJ-UHFFFAOYSA-N sodium;1h-1,2,4-triazole Chemical compound [Na].C=1N=CNN=1 MDUSUFIKBUMDTJ-UHFFFAOYSA-N 0.000 description 1
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- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
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- 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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- 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
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- 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
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-
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- 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
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- 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
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-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
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- 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
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- 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)
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| 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 |
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| US20190154661A1 (en) * | 2016-05-09 | 2019-05-23 | Proteostasis Therapeutics, Inc. | Methods of identifying cftr modulators |
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| US10047051B2 (en) | 2018-08-14 |
| HK1253581A1 (zh) | 2019-06-21 |
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