JP7221944B2 - ニコチン性アセチルコリン受容体のヘテロアリールアロステリックモジュレーター - Google Patents
ニコチン性アセチルコリン受容体のヘテロアリールアロステリックモジュレーター Download PDFInfo
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- JP7221944B2 JP7221944B2 JP2020515942A JP2020515942A JP7221944B2 JP 7221944 B2 JP7221944 B2 JP 7221944B2 JP 2020515942 A JP2020515942 A JP 2020515942A JP 2020515942 A JP2020515942 A JP 2020515942A JP 7221944 B2 JP7221944 B2 JP 7221944B2
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- Prior art keywords
- pyridine
- sulfonamide
- oxadiazol
- dimethylcyclopropyl
- alkyl
- 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.)
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- 125000001072 heteroaryl group Chemical group 0.000 title claims description 35
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title description 18
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 title description 18
- 230000003281 allosteric effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 206
- -1 NR 7 R 8 Chemical group 0.000 claims description 118
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 201000000980 schizophrenia Diseases 0.000 claims description 32
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 28
- 208000024827 Alzheimer disease Diseases 0.000 claims description 26
- 208000018737 Parkinson disease Diseases 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 208000010877 cognitive disease Diseases 0.000 claims description 24
- 208000028698 Cognitive impairment Diseases 0.000 claims description 21
- 239000003112 inhibitor Substances 0.000 claims description 20
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 15
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 15
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
- 229940124597 therapeutic agent Drugs 0.000 claims description 15
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 claims description 14
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 claims description 14
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 14
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
- 125000002971 oxazolyl group Chemical group 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- SYLXOKNUTSJDHC-LSDHHAIUSA-N 5-[(1S,3S)-3-(1,3-benzoxazol-2-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound O1C(=NC2=C1C=CC=C2)[C@@H]1C([C@H]1C=1C=CC(=NC=1)S(=O)(=O)N)(C)C SYLXOKNUTSJDHC-LSDHHAIUSA-N 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- SDZKOCYXPVZBIZ-QWHCGFSZSA-N 5-[(1R,2R)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound C1(=CC=CC=C1)C1=NOC(=N1)[C@H]1[C@@H](C1)C=1C=CC(=NC=1)S(=O)(=O)N SDZKOCYXPVZBIZ-QWHCGFSZSA-N 0.000 claims description 10
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 10
- IKXIGKUKPQKRNQ-ROUUACIJSA-N 5-[(1S,3S)-3-[5-(3-fluorophenyl)-1,2-oxazol-3-yl]-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound FC=1C=C(C=CC=1)C1=CC(=NO1)[C@@H]1C([C@H]1C=1C=CC(=NC=1)S(=O)(=O)N)(C)C IKXIGKUKPQKRNQ-ROUUACIJSA-N 0.000 claims description 9
- 102000010909 Monoamine Oxidase Human genes 0.000 claims description 9
- 108010062431 Monoamine oxidase Proteins 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 claims description 6
- 239000000164 antipsychotic agent Substances 0.000 claims description 6
- 229940005529 antipsychotics Drugs 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 229960004502 levodopa Drugs 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- GUEZCKQCMRKKGB-LSDHHAIUSA-N 5-[(1S,3S)-2,2-dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound C1(S(=O)(=O)N)=CC=C(C=N1)[C@H]1[C@H](C2=NC(=NO2)C2=CC=CC=C2)C1(C)C GUEZCKQCMRKKGB-LSDHHAIUSA-N 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- RHUCEFXXFYPRCA-VXGBXAGGSA-N 2-[(1S,3S)-2,2-dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound C1=CC=CC=C1C=1N=C([C@H]2[C@H](C3=NC=C(S(=O)(=O)N)S3)C2(C)C)ON=1 RHUCEFXXFYPRCA-VXGBXAGGSA-N 0.000 claims description 4
- BCCTVWZDKGLOBF-CABCVRRESA-N 5-[(1R,3R)-3-(3-cyclohexyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1CCCCC1 BCCTVWZDKGLOBF-CABCVRRESA-N 0.000 claims description 4
- SKXUNOWFUSLUHP-CVEARBPZSA-N 5-[(1R,3R)-3-(5-cyclopentyl-1,3-thiazol-2-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC=C(S1)C1CCCC1 SKXUNOWFUSLUHP-CVEARBPZSA-N 0.000 claims description 4
- BQZBENPENYNZRY-DLBZAZTESA-N 5-[(1S,3S)-2,2-dimethyl-3-(5-phenyl-1,3-oxazol-2-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound O=S(=O)(C1=NC=C(C=C1)[C@H]1[C@H](C=2OC(=CN=2)C2=CC=CC=C2)C1(C)C)N BQZBENPENYNZRY-DLBZAZTESA-N 0.000 claims description 4
- MBJLGTTZWPULDI-LSDHHAIUSA-N 5-[(1S,3S)-3-[5-(2,4-difluorophenyl)-1,3,4-thiadiazol-2-yl]-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound FC1=C(C=CC(=C1)F)C1=NN=C(S1)[C@@H]1C([C@H]1C=1C=CC(=NC=1)S(=O)(=O)N)(C)C MBJLGTTZWPULDI-LSDHHAIUSA-N 0.000 claims description 4
- KBLNCNFALKXIEG-LSDHHAIUSA-N 6-[(1S,3S)-2,2-dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-3-sulfonamide Chemical compound CC1([C@H]([C@@H]1C1=NC(=NO1)C1=CC=CC=C1)C1=CC=C(C=N1)S(=O)(=O)N)C KBLNCNFALKXIEG-LSDHHAIUSA-N 0.000 claims description 4
- ROPQAPAHCICQER-QWHCGFSZSA-N 6-[(1S,3S)-3-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-3-sulfonamide Chemical compound C1(CCC1)C1=NOC(=N1)[C@@H]1C([C@H]1C1=CC=C(C=N1)S(=O)(=O)N)(C)C ROPQAPAHCICQER-QWHCGFSZSA-N 0.000 claims description 4
- UUVXPCYCLCJBHQ-LSDHHAIUSA-N 6-[(1S,3S)-3-(3-cyclohexyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-3-sulfonamide Chemical compound O=S(=O)(C1=CN=C(C=C1)[C@H]1[C@@H](C1(C)C)C=1ON=C(N=1)C1CCCCC1)N UUVXPCYCLCJBHQ-LSDHHAIUSA-N 0.000 claims description 4
- SSOXAJCMKKQKJD-NWDGAFQWSA-N 6-[(1S,3S)-3-[3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]pyridine-3-sulfonamide Chemical class FC1(CC(C1)C1=NOC(=N1)[C@@H]1C([C@H]1C1=CC=C(C=N1)S(=O)(=O)N)(C)C)F SSOXAJCMKKQKJD-NWDGAFQWSA-N 0.000 claims description 4
- 229930194542 Keto Natural products 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000468 ketone group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- WGUBXAZEWVTJLK-IRXDYDNUSA-N 5-[(1S,3S)-3-(3-cyclopentyl-1,2-oxazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound C1(CCCC1)C1=NOC(=C1)[C@@H]1C([C@H]1C=1C=CC(=NC=1)S(=O)(=O)N)(C)C WGUBXAZEWVTJLK-IRXDYDNUSA-N 0.000 claims description 3
- NXHITWZDNFAGTQ-UONOGXRCSA-N 6-methyl-5-[(1R,2R)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1=C(C=CC(=N1)S(=O)(=O)N)[C@H]1[C@@H](C1)C1=NC(=NO1)C1=CC=CC=C1 NXHITWZDNFAGTQ-UONOGXRCSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- ZURYJDDVGAOKKK-NXEZZACHSA-N 2-[(1R,2R)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound C1(=CC=CC=C1)C1=NOC(=N1)[C@H]1[C@@H](C1)C=1SC(=CN=1)S(=O)(=O)N ZURYJDDVGAOKKK-NXEZZACHSA-N 0.000 claims description 2
- RHUCEFXXFYPRCA-RYUDHWBXSA-N 2-[(1R,3R)-2,2-dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=NC=C(S1)S(N)(=O)=O)C1=NC(=NO1)C1=CC=CC=C1 RHUCEFXXFYPRCA-RYUDHWBXSA-N 0.000 claims description 2
- HXBPPHLXYXHCAC-RKDXNWHRSA-N 2-[(1S,3S)-2,2-dimethyl-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)cyclopropyl]-1,3-thiazole-5-sulfonamide Chemical class CC1([C@H]([C@@H]1C1=NC(=NO1)C(C)C)C=1SC(=CN=1)S(=O)(=O)N)C HXBPPHLXYXHCAC-RKDXNWHRSA-N 0.000 claims description 2
- GNPKHWGYXFNRSK-VXGBXAGGSA-N 2-[(1S,3S)-3-(1,3-benzoxazol-2-yl)-2,2-dimethylcyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound O1C(=NC2=C1C=CC=C2)[C@@H]1C([C@H]1C=1SC(=CN=1)S(=O)(=O)N)(C)C GNPKHWGYXFNRSK-VXGBXAGGSA-N 0.000 claims description 2
- XLPXQBROYKPTPZ-NXEZZACHSA-N 2-[(1S,3S)-3-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound C1(CCC1)C1=NOC(=N1)[C@@H]1C([C@H]1C=1SC(=CN=1)S(=O)(=O)N)(C)C XLPXQBROYKPTPZ-NXEZZACHSA-N 0.000 claims description 2
- DZGGJEJBNFZMBV-RKDXNWHRSA-N 2-[(1S,3S)-3-[3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound FC1(CC(C1)C1=NOC(=N1)[C@@H]1C([C@H]1C=1SC(=CN=1)S(=O)(=O)N)(C)C)F DZGGJEJBNFZMBV-RKDXNWHRSA-N 0.000 claims description 2
- FWNBKMNABVPWPR-CHWSQXEVSA-N 2-[(1S,3S)-3-[3-(5-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound ClC=1C=CC(=C(C=1)C1=NOC(=N1)[C@@H]1C([C@H]1C=1SC(=CN=1)S(=O)(=O)N)(C)C)OC FWNBKMNABVPWPR-CHWSQXEVSA-N 0.000 claims description 2
- NXBOTBFWHAYCJM-GHMZBOCLSA-N 2-[(1S,3S)-3-[3-(5-fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]-1,3-thiazole-5-sulfonamide Chemical compound FC=1C=C(C=NC=1)C1=NOC(=N1)[C@@H]1C([C@H]1C=1SC(=CN=1)S(=O)(=O)N)(C)C NXBOTBFWHAYCJM-GHMZBOCLSA-N 0.000 claims description 2
- QXPRDUQWYCZOAN-NWDGAFQWSA-N 5-[(1R,2R)-2-(3-cyclopentyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound C1(CCCC1)C1=NOC(=N1)[C@H]1[C@@H](C1)C=1C=CC(=NC=1)S(=O)(=O)N QXPRDUQWYCZOAN-NWDGAFQWSA-N 0.000 claims description 2
- NPUOTYQKHOQNPW-QWHCGFSZSA-N 5-[(1R,2R)-2-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl]pyridine-2-sulfonamide Chemical compound FC=1C=C(C=CC=1)C1=NOC(=N1)[C@H]1[C@@H](C1)C=1C=CC(=NC=1)S(=O)(=O)N NPUOTYQKHOQNPW-QWHCGFSZSA-N 0.000 claims description 2
- GUEZCKQCMRKKGB-CABCVRRESA-N 5-[(1R,3R)-2,2-dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1=CC=CC=C1 GUEZCKQCMRKKGB-CABCVRRESA-N 0.000 claims description 2
- BQZBENPENYNZRY-SJORKVTESA-N 5-[(1R,3R)-2,2-dimethyl-3-(5-phenyl-1,3-oxazol-2-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC=C(O1)C1=CC=CC=C1 BQZBENPENYNZRY-SJORKVTESA-N 0.000 claims description 2
- JPFRLXKLJAYNLH-SJORKVTESA-N 5-[(1R,3R)-2,2-dimethyl-3-(5-phenyl-1,3-thiazol-2-yl)cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC=C(S1)C1=CC=CC=C1 JPFRLXKLJAYNLH-SJORKVTESA-N 0.000 claims description 2
- PCSPIBGWLBQLNV-CABCVRRESA-N 5-[(1R,3R)-2,2-dimethyl-3-[3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1=CC(=CC=C1)C(F)(F)F PCSPIBGWLBQLNV-CABCVRRESA-N 0.000 claims description 2
- UUGUOQXIMMBRIJ-KGLIPLIRSA-N 5-[(1R,3R)-2,2-dimethyl-3-[3-[5-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl]cyclopropyl]pyridine-2-sulfonamide Chemical compound CC1([C@@H]([C@H]1C1=NC(=NO1)C=1C=NC=C(C=1)C(F)(F)F)C=1C=CC(=NC=1)S(=O)(=O)N)C UUGUOQXIMMBRIJ-KGLIPLIRSA-N 0.000 claims description 2
- ARBCZKGQKCSGDR-OLZOCXBDSA-N 5-[(1R,3R)-3-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1CCC1 ARBCZKGQKCSGDR-OLZOCXBDSA-N 0.000 claims description 2
- DTJKVPXEOYTNRO-KGLIPLIRSA-N 5-[(1R,3R)-3-(3-cyclopentyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1CCCC1 DTJKVPXEOYTNRO-KGLIPLIRSA-N 0.000 claims description 2
- CSTTZLDCWWMAKN-CVEARBPZSA-N 5-[(1R,3R)-3-(5-cyclopentyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC=C(O1)C1CCCC1 CSTTZLDCWWMAKN-CVEARBPZSA-N 0.000 claims description 2
- RBXQVQOYVHNOCB-CABCVRRESA-N 5-[(1R,3R)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical class CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1=C(F)C=C(F)C=C1 RBXQVQOYVHNOCB-CABCVRRESA-N 0.000 claims description 2
- ZRGVFWRGFNCAJR-NEPJUHHUSA-N 5-[(1R,3R)-3-[3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical class CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1CC(F)(F)C1 ZRGVFWRGFNCAJR-NEPJUHHUSA-N 0.000 claims description 2
- AQLZBNMVDOOKRU-CABCVRRESA-N 5-[(1R,3R)-3-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl]pyridine-2-sulfonamide Chemical compound CC1(C)[C@@H]([C@H]1C1=CN=C(C=C1)S(N)(=O)=O)C1=NC(=NO1)C1=CC(F)=CC=C1 AQLZBNMVDOOKRU-CABCVRRESA-N 0.000 claims description 2
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Classifications
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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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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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
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- Hospice & Palliative Care (AREA)
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- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| US201762560444P | 2017-09-19 | 2017-09-19 | |
| US62/560,444 | 2017-09-19 | ||
| PCT/US2018/050975 WO2019060210A1 (en) | 2017-09-19 | 2018-09-14 | HETEROARYLIC ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS |
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| JP2020535127A JP2020535127A (ja) | 2020-12-03 |
| JP2020535127A5 JP2020535127A5 (enExample) | 2021-10-21 |
| JP7221944B2 true JP7221944B2 (ja) | 2023-02-14 |
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| US (1) | US11198687B2 (enExample) |
| EP (1) | EP3684357B1 (enExample) |
| JP (1) | JP7221944B2 (enExample) |
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| CA (1) | CA3073212A1 (enExample) |
| WO (1) | WO2019060210A1 (enExample) |
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| US11512092B2 (en) * | 2015-10-16 | 2022-11-29 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
| US11780848B2 (en) * | 2015-10-16 | 2023-10-10 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1- carboxamide and solid state forms thereof |
| US10357493B2 (en) | 2017-03-10 | 2019-07-23 | Selenity Therapeutics (Bermuda), Ltd. | Metalloenzyme inhibitor compounds |
| CN114727974A (zh) | 2019-07-30 | 2022-07-08 | 艾科尼佐治疗股份有限公司 | Hdac6抑制剂及其用途 |
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| WO2012103583A1 (en) | 2011-02-02 | 2012-08-09 | Bionomics Limited | Positive allosteric modulators of the alpha 7 nicotinic acetylcholine receptor and uses thereof. |
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| JP2015529651A (ja) | 2012-08-01 | 2015-10-08 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | α７ニコチン性アセチルコリン受容体モジュレーターおよびそれらの使用−Ｉ |
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| JP2012524752A (ja) | 2009-04-25 | 2012-10-18 | エフ．ホフマン−ラ ロシュ アーゲー | 複素環式抗ウイルス化合物 |
| WO2012103583A1 (en) | 2011-02-02 | 2012-08-09 | Bionomics Limited | Positive allosteric modulators of the alpha 7 nicotinic acetylcholine receptor and uses thereof. |
| JP2015529651A (ja) | 2012-08-01 | 2015-10-08 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | α７ニコチン性アセチルコリン受容体モジュレーターおよびそれらの使用−Ｉ |
| WO2015191799A1 (en) | 2014-06-13 | 2015-12-17 | Merck Sharp & Dohme Corp. | Alpha-7 nicotinic acetylcholine receptor modulators and uses thereof |
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| EP3684357A1 (en) | 2020-07-29 |
| EP3684357A4 (en) | 2021-01-20 |
| CA3073212A1 (en) | 2019-03-28 |
| WO2019060210A1 (en) | 2019-03-28 |
| CN111107846A (zh) | 2020-05-05 |
| US11198687B2 (en) | 2021-12-14 |
| US20200262826A1 (en) | 2020-08-20 |
| EP3684357B1 (en) | 2022-12-28 |
| JP2020535127A (ja) | 2020-12-03 |
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