CA2866015A1 - Thiazole derivatives as alpha 7 nachr modulators - Google Patents
Thiazole derivatives as alpha 7 nachr modulators Download PDFInfo
- Publication number
- CA2866015A1 CA2866015A1 CA2866015A CA2866015A CA2866015A1 CA 2866015 A1 CA2866015 A1 CA 2866015A1 CA 2866015 A CA2866015 A CA 2866015A CA 2866015 A CA2866015 A CA 2866015A CA 2866015 A1 CA2866015 A1 CA 2866015A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- alkyl
- unsubstituted
- thiazol
- benzenesulfonamide
- 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.)
- Abandoned
Links
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- 150000001875 compounds Chemical class 0.000 claims abstract description 246
- 238000000034 method Methods 0.000 claims abstract description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 57
- 150000003839 salts Chemical class 0.000 claims abstract description 34
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- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims abstract description 11
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims abstract description 11
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- 125000000217 alkyl group Chemical group 0.000 claims description 155
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 150
- -1 cyano, hydroxy Chemical group 0.000 claims description 107
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 73
- 125000004432 carbon atom Chemical group C* 0.000 claims description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
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- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
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- HHPRYROIORWJNO-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.2.1]octane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CCC(C3)C2)S1 HHPRYROIORWJNO-UHFFFAOYSA-N 0.000 claims description 3
- QABSWFDRJDYHHS-UHFFFAOYSA-N 4-[2-(8-azabicyclo[3.2.1]octane-8-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3CCC2CCC3)S1 QABSWFDRJDYHHS-UHFFFAOYSA-N 0.000 claims description 3
- IUFIXLZAMRLPCO-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,5-dimethylpiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1C(C)CC(C)CN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IUFIXLZAMRLPCO-UHFFFAOYSA-N 0.000 claims description 3
- YRBJUBCAOVBLRM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3CCC2COC3)S1 YRBJUBCAOVBLRM-UHFFFAOYSA-N 0.000 claims description 3
- DCXLWPYCCHASCW-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CCC(O3)C2)S1 DCXLWPYCCHASCW-UHFFFAOYSA-N 0.000 claims description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- KDNUUYOYBHDNDM-UHFFFAOYSA-N C12CN(CC(O1)C2)C(=O)C=2SC(=C(N2)C2=CC=C(C=C2)Cl)C2=CC=C(C=C2)S(=O)(=O)N Chemical compound C12CN(CC(O1)C2)C(=O)C=2SC(=C(N2)C2=CC=C(C=C2)Cl)C2=CC=C(C=C2)S(=O)(=O)N KDNUUYOYBHDNDM-UHFFFAOYSA-N 0.000 claims description 3
- AQEIATKGDMRYRX-CQSZACIVSA-N C[C@@H]1CN(CCN1C)C(=O)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 Chemical compound C[C@@H]1CN(CCN1C)C(=O)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 AQEIATKGDMRYRX-CQSZACIVSA-N 0.000 claims description 3
- QVQPGNFBJIKHRW-CQSZACIVSA-N C[C@@H]1CN(CCN1C)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 Chemical compound C[C@@H]1CN(CCN1C)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 QVQPGNFBJIKHRW-CQSZACIVSA-N 0.000 claims description 3
- 208000015943 Coeliac disease Diseases 0.000 claims description 3
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- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
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- IEVWKUXXENKPFC-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2CC3CC3C2)S1 IEVWKUXXENKPFC-UHFFFAOYSA-N 0.000 claims description 2
- VNIOUJLTHHFDDZ-YPXDRJKUSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C12CN(CC2C1)C(=O)C=1SC(=C(N1)N1C[C@@H](O[C@@H](C1)C)C)C1=CC=C(C=C1)S(=O)(=O)N VNIOUJLTHHFDDZ-YPXDRJKUSA-N 0.000 claims description 2
- RQYTUIALCMVIGO-OKILXGFUSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-fluorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 RQYTUIALCMVIGO-OKILXGFUSA-N 0.000 claims description 2
- HXHCOMLCGVBEMM-IYBDPMFKSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-methylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(C)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 HXHCOMLCGVBEMM-IYBDPMFKSA-N 0.000 claims description 2
- SDUPQAWNTFPSPW-BETUJISGSA-N 4-[4-(2,4-difluorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C(=CC(F)=CC=2)F)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 SDUPQAWNTFPSPW-BETUJISGSA-N 0.000 claims description 2
- IHGKJDJXIMUVIE-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(2-oxopiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(CCCC2)=O)S1 IHGKJDJXIMUVIE-UHFFFAOYSA-N 0.000 claims description 2
- OPTQOTSMHGTWRS-OKILXGFUSA-N 4-[4-(4-chlorophenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound ClC1=CC=C(C=C1)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C OPTQOTSMHGTWRS-OKILXGFUSA-N 0.000 claims description 2
- IUFIXLZAMRLPCO-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(3r,5s)-3,5-dimethylpiperidin-1-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)C[C@@H](C)CN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IUFIXLZAMRLPCO-GASCZTMLSA-N 0.000 claims description 2
- ZNTASJHFBDFQDH-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(3s,5r)-3,5-dimethylpiperidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)C[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 ZNTASJHFBDFQDH-GASCZTMLSA-N 0.000 claims description 2
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 29
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 3
- QAXOZZQNRMADMD-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-3-yl-[4-(4-chlorophenyl)-5-(4-piperidin-1-ylsulfonylphenyl)-1,3-thiazol-2-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C1=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCCCC2)SC(C(=O)N2CC3CC3C2)=N1 QAXOZZQNRMADMD-UHFFFAOYSA-N 0.000 claims 1
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- PTVBZABDPBNCCM-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chloro-3-methylphenyl)-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1=C(Cl)C(C)=CC(C2=C(SC(=N2)C(=O)N2CC3CC3C2)C=2C=C(F)C(=CC=2)S(N)(=O)=O)=C1 PTVBZABDPBNCCM-UHFFFAOYSA-N 0.000 claims 1
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- MIAZICXDLFGPCN-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.2.1]octan-3-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CCC(C3)C2)S1 MIAZICXDLFGPCN-UHFFFAOYSA-N 0.000 claims 1
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- XJOJJWZDTJKVNT-UHFFFAOYSA-N 4-[2-(5-azaspiro[2.5]octan-5-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3(CC3)CCC2)S1 XJOJJWZDTJKVNT-UHFFFAOYSA-N 0.000 claims 1
- PKFDOEZPBHUKHR-UHFFFAOYSA-N 4-[2-(5-azaspiro[2.5]octane-5-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3(CC3)CCC2)S1 PKFDOEZPBHUKHR-UHFFFAOYSA-N 0.000 claims 1
- TWPBEZZDBVJXSD-UHFFFAOYSA-N 4-[2-(6-azaspiro[2.5]octan-6-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCC3(CC3)CC2)S1 TWPBEZZDBVJXSD-UHFFFAOYSA-N 0.000 claims 1
- FDYIEEYOPXIXIK-UHFFFAOYSA-N 4-[2-(6-azaspiro[2.5]octane-6-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCC3(CC3)CC2)S1 FDYIEEYOPXIXIK-UHFFFAOYSA-N 0.000 claims 1
- MFYGYYLTOHYNNM-UHFFFAOYSA-N 4-[2-(8-azabicyclo[3.2.1]octan-8-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3CCC2CCC3)S1 MFYGYYLTOHYNNM-UHFFFAOYSA-N 0.000 claims 1
- JAMMKRPUIDPFTG-IYBDPMFKSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(1-methylindol-5-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3C=CN(C)C3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 JAMMKRPUIDPFTG-IYBDPMFKSA-N 0.000 claims 1
- KGTVYBWNGBGBLQ-GASCZTMLSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(1h-indol-5-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3C=CNC3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 KGTVYBWNGBGBLQ-GASCZTMLSA-N 0.000 claims 1
- MQTUZZYWTJLHLF-GASCZTMLSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-methylsulfonylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)S(C)(=O)=O)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 MQTUZZYWTJLHLF-GASCZTMLSA-N 0.000 claims 1
- CCZSJZCJSWRKLZ-OKILXGFUSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)C(F)(F)F)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 CCZSJZCJSWRKLZ-OKILXGFUSA-N 0.000 claims 1
- CMEQUZWIYUHYFF-UHFFFAOYSA-N 4-[2-[2,6-bis(fluoromethyl)morpholine-4-carbonyl]-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC(CF)OC(CF)C2)S1 CMEQUZWIYUHYFF-UHFFFAOYSA-N 0.000 claims 1
- NEACZCRXQGHXKS-UHFFFAOYSA-N 4-[4-(1-acetyl-2,3-dihydroindol-5-yl)-2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1C=1N=C(C(=O)N2CC3CC3C2)SC=1C1=CC=C(S(N)(=O)=O)C=C1 NEACZCRXQGHXKS-UHFFFAOYSA-N 0.000 claims 1
- IFKBWQYSWMSHJE-IYBDPMFKSA-N 4-[4-(1-acetyl-2,3-dihydroindol-5-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3CCN(C3=CC=2)C(C)=O)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IFKBWQYSWMSHJE-IYBDPMFKSA-N 0.000 claims 1
- HDVJPHGVKBJOLQ-IYBDPMFKSA-N 4-[4-(2,3-dihydro-1h-inden-5-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3CCCC3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 HDVJPHGVKBJOLQ-IYBDPMFKSA-N 0.000 claims 1
- UEBYLRSONWTNEI-BETUJISGSA-N 4-[4-(3,4-difluorophenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound FC=1C=C(C=CC1F)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C UEBYLRSONWTNEI-BETUJISGSA-N 0.000 claims 1
- NZZPVZIOAQKPHI-GASCZTMLSA-N 4-[4-(4-chloro-2,3-dihydroindol-1-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(N2C3=C(C(=CC=C3)Cl)CC2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 NZZPVZIOAQKPHI-GASCZTMLSA-N 0.000 claims 1
- GMWBLASSFYGVGG-GASCZTMLSA-N 4-[4-(4-chloro-3-cyclopropylphenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound ClC1=C(C=C(C=C1)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C)C1CC1 GMWBLASSFYGVGG-GASCZTMLSA-N 0.000 claims 1
- QHFAVPQTOJLULP-UHFFFAOYSA-N 4-[4-(4-chloro-3-methylphenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(C)=CC(C2=C(SC(=N2)C(=O)N2CCCC2)C=2C=CC(=CC=2)S(N)(=O)=O)=C1 QHFAVPQTOJLULP-UHFFFAOYSA-N 0.000 claims 1
- SYODNVDXNGZXCD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(2-oxopyrrolidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(CCC2)=O)S1 SYODNVDXNGZXCD-UHFFFAOYSA-N 0.000 claims 1
- QTCVHVBCVNRHRW-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,3-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC(F)(F)CCC2)S1 QTCVHVBCVNRHRW-UHFFFAOYSA-N 0.000 claims 1
- AOHRWSRNFNZKOD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-1h-isoquinolin-2-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3=CC=CC=C3CC2)S1 AOHRWSRNFNZKOD-UHFFFAOYSA-N 0.000 claims 1
- SJVXUXCUVBLGGF-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3=CC=CC=C3CC2)S1 SJVXUXCUVBLGGF-UHFFFAOYSA-N 0.000 claims 1
- AULNCWIVHQPAQL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-2h-quinolin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3=CC=CC=C3CCC2)S1 AULNCWIVHQPAQL-UHFFFAOYSA-N 0.000 claims 1
- WPXARWUIISVXRJ-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-2h-quinoline-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3=CC=CC=C3CCC2)S1 WPXARWUIISVXRJ-UHFFFAOYSA-N 0.000 claims 1
- ZNTASJHFBDFQDH-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,5-dimethylpiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1C(C)CC(C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 ZNTASJHFBDFQDH-UHFFFAOYSA-N 0.000 claims 1
- UXADRPPBRNCNIG-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3CCC2COC3)S1 UXADRPPBRNCNIG-UHFFFAOYSA-N 0.000 claims 1
- PVCWAUMYAZEZEO-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxomorpholin-4-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(COCC2)=O)S1 PVCWAUMYAZEZEO-UHFFFAOYSA-N 0.000 claims 1
- UUBINWDQLDCNHK-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4,4-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]-2-methylbenzenesulfonamide Chemical compound C1=C(S(N)(=O)=O)C(C)=CC(C2=C(N=C(S2)C(=O)N2CCC(F)(F)CC2)C=2C=CC(Cl)=CC=2)=C1 UUBINWDQLDCNHK-UHFFFAOYSA-N 0.000 claims 1
- FXYICNFGXADGMB-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4,4-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCC(F)(F)CC2)S1 FXYICNFGXADGMB-UHFFFAOYSA-N 0.000 claims 1
- XKAZMQLDGJPZNL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4-phenylpiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCC(CC2)C=2C=CC=CC=2)S1 XKAZMQLDGJPZNL-UHFFFAOYSA-N 0.000 claims 1
- FKJVBFOGHYDWCE-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CC(O3)C2)S1 FKJVBFOGHYDWCE-UHFFFAOYSA-N 0.000 claims 1
- ORRSAEAVTRLDDG-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CCC(O3)C2)S1 ORRSAEAVTRLDDG-UHFFFAOYSA-N 0.000 claims 1
- JMRPASLWEHEDQD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(morpholine-4-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCOCC2)S1 JMRPASLWEHEDQD-UHFFFAOYSA-N 0.000 claims 1
- ZFMBUEKNELBRKL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(piperidine-1-carbonyl)-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCCC2)S1 ZFMBUEKNELBRKL-UHFFFAOYSA-N 0.000 claims 1
- ZWTPORONWDKZGA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(piperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCCC2)S1 ZWTPORONWDKZGA-UHFFFAOYSA-N 0.000 claims 1
- CSXODYWJASTLNM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 CSXODYWJASTLNM-UHFFFAOYSA-N 0.000 claims 1
- HTUMOEGBXYRUNR-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 HTUMOEGBXYRUNR-UHFFFAOYSA-N 0.000 claims 1
- OBNPWWMQBOKERA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 OBNPWWMQBOKERA-UHFFFAOYSA-N 0.000 claims 1
- CNROLYYCONHXGT-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-[(2-oxopiperidin-1-yl)methyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2C(CCCC2)=O)S1 CNROLYYCONHXGT-UHFFFAOYSA-N 0.000 claims 1
- FZVJATOSCCZIAA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-[(2-oxopyrrolidin-1-yl)methyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2C(CCC2)=O)S1 FZVJATOSCCZIAA-UHFFFAOYSA-N 0.000 claims 1
- STINCJLJSYRNAX-INIZCTEOSA-N 4-[4-(4-chlorophenyl)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2[C@@H](CCC2)C#N)S1 STINCJLJSYRNAX-INIZCTEOSA-N 0.000 claims 1
- PIJNYIPTGOMPIA-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-(trifluoromethyl)benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(C(=CC=2)S(N)(=O)=O)C(F)(F)F)S1 PIJNYIPTGOMPIA-BETUJISGSA-N 0.000 claims 1
- NABONUMFCNUCIL-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(F)C(=CC=2)S(N)(=O)=O)S1 NABONUMFCNUCIL-BETUJISGSA-N 0.000 claims 1
- PBTFUHYZJJLKKL-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-methylbenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(C)C(=CC=2)S(N)(=O)=O)S1 PBTFUHYZJJLKKL-GASCZTMLSA-N 0.000 claims 1
- KKACYNBLQLCBEM-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C(=CC(=CC=2)S(N)(=O)=O)F)S1 KKACYNBLQLCBEM-BETUJISGSA-N 0.000 claims 1
- CPOAHPILTHHLOX-IYBDPMFKSA-N 4-[4-(4-chlorophenyl)-2-[(3r,5s)-3,5-difluoropiperidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C[C@H](F)C[C@H](F)C2)S1 CPOAHPILTHHLOX-IYBDPMFKSA-N 0.000 claims 1
- HQQDTFLZRUUATI-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-morpholin-4-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCOCC2)S1 HQQDTFLZRUUATI-UHFFFAOYSA-N 0.000 claims 1
- JGNLVVXJSKGKBU-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-piperidin-1-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCCCC2)S1 JGNLVVXJSKGKBU-UHFFFAOYSA-N 0.000 claims 1
- RXFBZQNOQLCMSJ-GASCZTMLSA-N 4-[4-(4-cyanophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)C#N)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 RXFBZQNOQLCMSJ-GASCZTMLSA-N 0.000 claims 1
- DISYJFOTLSTWJF-IYBDPMFKSA-N 4-[4-(4-cyclopropylphenyl)-2-[(2r,6s)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)C2CC2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 DISYJFOTLSTWJF-IYBDPMFKSA-N 0.000 claims 1
- IZMPDWSNIQNZSR-IYBDPMFKSA-N 4-[4-[4-(dimethylamino)phenyl]-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)N(C)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IZMPDWSNIQNZSR-IYBDPMFKSA-N 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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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
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- 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
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- 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
- A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D417/06—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 only aliphatic carbon atoms
-
- 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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- Chemical & Material Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
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| IN236/KOL/2012 | 2012-03-06 | ||
| IN237KO2012 | 2012-03-06 | ||
| IN237/KOL/2012 | 2012-03-06 | ||
| IN235/KOL/2012 | 2012-03-06 | ||
| IN235KO2012 | 2012-03-06 | ||
| IN236KO2012 | 2012-03-06 | ||
| IN1307KO2012 | 2012-11-12 | ||
| IN1307/KOL/2012 | 2012-11-12 | ||
| PCT/IB2013/051455 WO2013132380A1 (en) | 2012-03-06 | 2013-02-22 | Thiazole derivatives as alpha 7 nachr modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2866015A1 true CA2866015A1 (en) | 2013-09-12 |
Family
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Family Applications (1)
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| CA2866015A Abandoned CA2866015A1 (en) | 2012-03-06 | 2013-02-22 | Thiazole derivatives as alpha 7 nachr modulators |
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| US (1) | US9388196B2 (forum.php) |
| EP (1) | EP2822946A1 (forum.php) |
| AU (1) | AU2013229177B2 (forum.php) |
| CA (1) | CA2866015A1 (forum.php) |
| IN (1) | IN2014MN01756A (forum.php) |
| NZ (1) | NZ629453A (forum.php) |
| SG (1) | SG11201405239WA (forum.php) |
| WO (1) | WO2013132380A1 (forum.php) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2014014614A (es) | 2012-05-31 | 2015-02-12 | Phenex Pharmaceuticals Ag | Tiazoles sustituidos por carboxamida o sulfonamida y derivados relacionados como moduladores para el receptor nuclear huerfano ror [gamma). |
| WO2014072957A1 (en) * | 2012-11-12 | 2014-05-15 | Lupin Limited | Thiazole derivatives as alpha 7 nachr modulators |
| WO2014141091A1 (en) | 2013-03-13 | 2014-09-18 | Lupin Limited | Pyrrole derivatives as alpha 7 nachr modulators |
| TW201446243A (zh) | 2013-06-03 | 2014-12-16 | Lupin Ltd | 4-(5-(4-氯苯基)-2-(2-環丙基乙醯基)-1,4-二甲基-1氫-吡咯-3-基)苯磺醯胺作為α7尼古丁乙醯膽鹼受體調節劑 |
| AU2014282886A1 (en) | 2013-06-17 | 2015-12-17 | Lupin Limited | Pyrrole derivatives as alpha 7 nAChR modulators |
| BR112017000043A2 (pt) * | 2014-07-03 | 2018-07-17 | Celgene Quanticel Research, Inc. | inibidores da desmetilase específica de lisina-1 |
| EP3623371A1 (en) | 2014-12-16 | 2020-03-18 | Axovant Sciences GmbH | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| AU2016274694A1 (en) | 2015-06-10 | 2018-01-18 | Axovant Sciences Gmbh | Aminobenzisoxazole compounds as agonists of A7-nicotinic acetylcholine receptors |
| EP3325473A4 (en) | 2015-07-22 | 2019-06-26 | The Royal Institution for the Advancement of Learning / McGill University | Compounds and uses thereof in the treatment of cancer and other medical disorders |
| EP3334740A4 (en) | 2015-08-12 | 2019-02-06 | Axovant Sciences GmbH | GEMINAL SUBSTITUTED AMINOBENZISOXAZOLE COMPOUNDS AS AGONISTS OF ALPHA 7-NICOTINIC ACETYLCHOLINE RECEPTORS |
| CN108101860B (zh) * | 2018-02-08 | 2021-11-23 | 苏州敬业医药化工有限公司 | 顺式-2，6-二甲基吗啉的制备方法 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3953596A (en) | 1973-06-14 | 1976-04-27 | Ici United States Inc. | 8-Oxa-3-azabicyclo(3.2.1)octane analgesic compositions and method of alleviating pain in animals |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| JPH10504542A (ja) * | 1994-07-27 | 1998-05-06 | ジー．ディー．サール アンド カンパニー | 炎症処置用の置換チアゾール化合物 |
| US5608082A (en) | 1994-07-28 | 1997-03-04 | Agouron Pharmaceuticals, Inc. | Compounds useful as antiproliferative agents and GARFT inhibitors |
| ES2226167T3 (es) | 1997-09-12 | 2005-03-16 | MERCK FROSST CANADA & CO. | Piridinas 2,3,5-sustituidas como inhibidores de ciclooxigenasa 2. |
| US7514452B2 (en) | 2002-02-01 | 2009-04-07 | Dainippon Pharmaceutical Co., Ltd | 2-furancarboxylic acid hydrazides and pharmaceutical compositions containing the same |
| US7202367B2 (en) | 2002-05-31 | 2007-04-10 | Rhodia Chimie | Process for arylating or vinylating or alkynating a nucleophilic compound |
| SE0201938D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New process |
| DE10244810A1 (de) | 2002-09-26 | 2004-04-08 | Bayer Ag | Neue Morpholin-überbrückte Indazolderivate |
| US7129235B2 (en) | 2003-07-11 | 2006-10-31 | Abbott Laboratories | Amides useful for treating pain |
| US7442805B2 (en) | 2003-09-25 | 2008-10-28 | Wyeth | Substituted sulfonamide-indoles |
| GB0403038D0 (en) | 2004-02-11 | 2004-03-17 | Novartis Ag | Organic compounds |
| EP1732883A1 (en) | 2004-03-29 | 2006-12-20 | Neurosearch A/S | Novel urea derivatives and their medical use |
| ITTO20040264A1 (it) | 2004-04-28 | 2004-07-28 | Rotta Res Lab Spa | Nuovi derivati pirrolici ad attivita' angiotensina-ii antagonista |
| CN101048381A (zh) | 2004-09-09 | 2007-10-03 | 中外制药株式会社 | 新型四氢咪唑衍生物及其用途 |
| US20060142349A1 (en) | 2004-12-23 | 2006-06-29 | Pfizer Inc | Methods of modulating the activities of alpha-7 nicotinic acetylcholine receptor |
| EP1866314B1 (en) | 2005-02-16 | 2010-09-15 | NeuroSearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| FR2885616B1 (fr) | 2005-05-12 | 2007-06-22 | Servier Lab | Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US20070032531A1 (en) | 2005-08-04 | 2007-02-08 | Apogee Biotechnology Corporation | Sphingosine kinase inhibitors and methods of their use |
| EA015034B1 (ru) | 2005-09-13 | 2011-04-29 | Янссен Фармацевтика Н.В. | 2-анилин-4-арилзамещенные тиазольные производные |
| US7863302B2 (en) | 2006-02-03 | 2011-01-04 | Eli Lilly And Company | Compounds and methods for modulating FX-receptors |
| WO2007093602A1 (en) | 2006-02-16 | 2007-08-23 | Neurosearch A/S | Enantiopure quinuclidinyloxy pyridazines and their use as nicotinic acetylcholine receptor ligands |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| AU2007265116A1 (en) * | 2006-06-27 | 2008-01-03 | Abbott Laboratories | Pyrrole derivatives and their methods of use |
| TW200813000A (en) | 2006-06-27 | 2008-03-16 | Abbott Lab | Thiazoline and oxazoline derivatives and their methods of use |
| JP2010509216A (ja) | 2006-11-02 | 2010-03-25 | メルク エンド カムパニー インコーポレーテッド | ヘテロシクリル置換抗高コレステロール血症化合物 |
| US20080287479A1 (en) | 2006-12-20 | 2008-11-20 | Pfizer Inc | Inhibitors of serine palmitoyltransferase |
| MX2010001135A (es) | 2007-08-08 | 2010-03-09 | Neurosearch As | Nuevos derivados de 1,2,3-triazol, utiles como modulares de receptores de acetilcolina nicotinicos. |
| GB0718735D0 (en) | 2007-09-25 | 2007-11-07 | Prolysis Ltd | Antibacterial agents |
| CN101821246B (zh) | 2007-10-04 | 2013-05-01 | 弗·哈夫曼-拉罗切有限公司 | 四唑取代的芳基酰胺衍生物及其用途 |
| AU2008307195B2 (en) | 2007-10-04 | 2012-11-22 | F. Hoffmann-La Roche Ag | Cyclopropyl aryl amide derivatives and uses thereof |
| JO2784B1 (en) | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| CL2009000662A1 (es) | 2008-03-19 | 2010-02-05 | Janssen Pharmaceutica Nv | Compuestos derivados de 1,2,4-triazol trisustituidos, moduladores del receptor de acetilcolina nicotinicos; composicion farmaceutica; su proceso de preparacion; y uso para la prevencion o el tratamiento de trastornos psicoticos, trastornos o enfermedades de daño intelectual, o enfermedades o trastornos inflamatorios. |
| US7786171B2 (en) | 2008-04-04 | 2010-08-31 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
| CN102066356B (zh) | 2008-04-17 | 2014-06-11 | 葛兰素集团有限公司 | 作为α7烟碱型乙酰胆碱受体亚型调节剂的吲哚衍生物 |
| CN102015655A (zh) | 2008-05-09 | 2011-04-13 | 詹森药业有限公司 | 作为乙酰胆碱受体调节剂的三取代吡唑类 |
| WO2010083444A1 (en) | 2009-01-15 | 2010-07-22 | Anvyl, Llc | Alpha7 nicotinic acetylcholine receptor allosteric modulators, their derivatives and uses thereof |
| WO2010120854A1 (en) | 2009-04-15 | 2010-10-21 | Glaxosmithkline Llc | Chemical compounds |
| US20120071469A1 (en) | 2009-05-14 | 2012-03-22 | Neurosearch A/S | Novel 1,4-diaza-bicyclo[3.2.1]octane derivatives useful as nicotinic acetylcholine receptor modulators |
| TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α７活化劑之用途 |
| JO3078B1 (ar) | 2009-11-27 | 2017-03-15 | Janssen Pharmaceutica Nv | مورفولينوثيازولات بصفتها منظمات الوستيرية نوع الفا 7 موجبة |
| US20130310419A1 (en) | 2011-02-03 | 2013-11-21 | Lupin Limited | Pyrrole derivatives used as modulators of alpha7 nachr |
| PH12013501727A1 (en) | 2011-02-23 | 2013-10-07 | Lupin Ltd | Heteroaryl derivatives as alpha7 nachr modulators |
| SG193387A1 (en) | 2011-03-31 | 2013-10-30 | Lupin Ltd | Pyrrole derivatives as nicotinic acetylcholine receptor modulators for use in the treatment of neurodegenerative disorders such as alzheimer's and parkinson's disease |
| WO2013005153A1 (en) | 2011-07-05 | 2013-01-10 | Lupin Limited | Biaryl derivatives as nachr modulators |
-
2013
- 2013-02-22 AU AU2013229177A patent/AU2013229177B2/en not_active Expired - Fee Related
- 2013-02-22 NZ NZ629453A patent/NZ629453A/en not_active IP Right Cessation
- 2013-02-22 US US14/379,134 patent/US9388196B2/en not_active Expired - Fee Related
- 2013-02-22 WO PCT/IB2013/051455 patent/WO2013132380A1/en active Application Filing
- 2013-02-22 EP EP13711972.3A patent/EP2822946A1/en not_active Withdrawn
- 2013-02-22 IN IN1756MUN2014 patent/IN2014MN01756A/en unknown
- 2013-02-22 SG SG11201405239WA patent/SG11201405239WA/en unknown
- 2013-02-22 CA CA2866015A patent/CA2866015A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013229177B2 (en) | 2017-03-23 |
| EP2822946A1 (en) | 2015-01-14 |
| US20150291617A1 (en) | 2015-10-15 |
| WO2013132380A1 (en) | 2013-09-12 |
| NZ629453A (en) | 2016-04-29 |
| IN2014MN01756A (forum.php) | 2015-07-03 |
| SG11201405239WA (en) | 2014-09-26 |
| US9388196B2 (en) | 2016-07-12 |
| AU2013229177A1 (en) | 2014-09-18 |
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