JP2001506646A - スルホンアミド誘導体、それらの製造方法、および医薬としてのそれらの使用 - Google Patents
スルホンアミド誘導体、それらの製造方法、および医薬としてのそれらの使用Info
- Publication number
- JP2001506646A JP2001506646A JP52734798A JP52734798A JP2001506646A JP 2001506646 A JP2001506646 A JP 2001506646A JP 52734798 A JP52734798 A JP 52734798A JP 52734798 A JP52734798 A JP 52734798A JP 2001506646 A JP2001506646 A JP 2001506646A
- Authority
- JP
- Japan
- Prior art keywords
- methoxy
- phenyl
- methylpiperazin
- benzenesulfonamide
- chloro
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 43
- 229940124530 sulfonamide Drugs 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 239000003814 drug Substances 0.000 title abstract description 8
- 150000003456 sulfonamides Chemical class 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 117
- -1 Hydroxy, hydroxy Chemical group 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 54
- 150000001408 amides Chemical class 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- GXWGRQOMOLFZDN-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2C(C)=C(S(O)(=O)=O)SC2=C1 GXWGRQOMOLFZDN-UHFFFAOYSA-N 0.000 claims description 26
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052717 sulfur Chemical group 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 8
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- PAVQGEMIVJDBJU-UHFFFAOYSA-N 1-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]-5-methoxy-6-(4-methylpiperazin-1-yl)-2,3-dihydroindole Chemical compound COC1=CC=2CCN(S(=O)(=O)C3=C(C4=CC(Cl)=CC=C4S3)C)C=2C=C1N1CCN(C)CC1 PAVQGEMIVJDBJU-UHFFFAOYSA-N 0.000 claims description 3
- ZFZRYSSNJATGEN-UHFFFAOYSA-N 2,3-dichloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(Cl)=C1Cl ZFZRYSSNJATGEN-UHFFFAOYSA-N 0.000 claims description 3
- MZDBZBQDHGJUCJ-UHFFFAOYSA-N 5-chloro-n-[3-[2-(dimethylamino)ethoxy]-4-iodophenyl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound C1=C(I)C(OCCN(C)C)=CC(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)=C1 MZDBZBQDHGJUCJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- FGBDZGNJGHTZCH-UHFFFAOYSA-N n-[3-(4-benzylpiperazin-1-yl)-4-methoxyphenyl]-5-chloro-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)C=C1N(CC1)CCN1CC1=CC=CC=C1 FGBDZGNJGHTZCH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 150000004885 piperazines Chemical group 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- BSXLLFUSNQCWJP-UHFFFAOYSA-N thiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-N 0.000 claims description 3
- DHRIBEBTNXSRGD-UHFFFAOYSA-N 1-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]-6-(4-methylpiperazin-1-yl)-2,3-dihydroindole Chemical compound C1CN(C)CCN1C1=CC=C(CCN2S(=O)(=O)C3=C(C4=CC(Cl)=CC=C4S3)C)C2=C1 DHRIBEBTNXSRGD-UHFFFAOYSA-N 0.000 claims description 2
- LFQDZSZMCJKAHG-UHFFFAOYSA-N 1-benzofuran-2-sulfonic acid Chemical compound C1=CC=C2OC(S(=O)(=O)O)=CC2=C1 LFQDZSZMCJKAHG-UHFFFAOYSA-N 0.000 claims description 2
- LIQUPAWMSXBLKH-UHFFFAOYSA-N 2,3,4-trichloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(Cl)C(Cl)=C1Cl LIQUPAWMSXBLKH-UHFFFAOYSA-N 0.000 claims description 2
- LILAGPSTPBGPKR-UHFFFAOYSA-N 2,5-dichloro-n-(4-methoxy-3-piperazin-1-ylphenyl)thiophene-3-sulfonamide Chemical compound C1=C(N2CCNCC2)C(OC)=CC=C1NS(=O)(=O)C=1C=C(Cl)SC=1Cl LILAGPSTPBGPKR-UHFFFAOYSA-N 0.000 claims description 2
- BNTOKXVZDOERDS-UHFFFAOYSA-N 2,5-dichloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]thiophene-3-sulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C=1C=C(Cl)SC=1Cl BNTOKXVZDOERDS-UHFFFAOYSA-N 0.000 claims description 2
- GZBPVVJNBJRWDU-UHFFFAOYSA-N 2,5-dimethoxy-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound COC1=CC=C(OC)C(S(=O)(=O)NC=2C=C(C(OC)=CC=2)N2CCN(C)CC2)=C1 GZBPVVJNBJRWDU-UHFFFAOYSA-N 0.000 claims description 2
- OVRVKGKPURKVHI-UHFFFAOYSA-N 2-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC=C1Cl OVRVKGKPURKVHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- ZGQQPCNPKWFNJZ-UHFFFAOYSA-N 3,4-dimethoxy-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)NC1=CC=C(OC)C(N2CCN(C)CC2)=C1 ZGQQPCNPKWFNJZ-UHFFFAOYSA-N 0.000 claims description 2
- UDJMZYLDIFOZMO-UHFFFAOYSA-N 3,5-dichloro-n-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide Chemical compound C1=C(N2CCNCC2)C(OC)=CC=C1NS(=O)(=O)C1=CC(Cl)=CC(Cl)=C1 UDJMZYLDIFOZMO-UHFFFAOYSA-N 0.000 claims description 2
- UCVPQLPCDDLJEJ-UHFFFAOYSA-N 3-bromo-5-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]thiophene-2-sulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C=1SC(Cl)=CC=1Br UCVPQLPCDDLJEJ-UHFFFAOYSA-N 0.000 claims description 2
- YFYIBXVPGOQPQR-UHFFFAOYSA-N 3-bromo-5-chloro-n-[7-(4-methylpiperazin-1-yl)-2,3-dihydro-1-benzofuran-5-yl]thiophene-2-sulfonamide Chemical compound C1CN(C)CCN1C1=CC(NS(=O)(=O)C2=C(C=C(Cl)S2)Br)=CC2=C1OCC2 YFYIBXVPGOQPQR-UHFFFAOYSA-N 0.000 claims description 2
- FPCXZHNKUCICKB-UHFFFAOYSA-N 3-bromo-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(Br)=C1 FPCXZHNKUCICKB-UHFFFAOYSA-N 0.000 claims description 2
- RUWCPIWOUKKUHW-UHFFFAOYSA-N 3-chloro-n-(4-methoxy-3-piperazin-1-ylphenyl)-4-methylbenzenesulfonamide Chemical compound C1=C(N2CCNCC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(C)C(Cl)=C1 RUWCPIWOUKKUHW-UHFFFAOYSA-N 0.000 claims description 2
- FOJBAYHRQHCRAZ-UHFFFAOYSA-N 3-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-methylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(C)C(Cl)=C1 FOJBAYHRQHCRAZ-UHFFFAOYSA-N 0.000 claims description 2
- GMGHATXHJRZOAP-UHFFFAOYSA-N 3-fluoro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(F)=C1 GMGHATXHJRZOAP-UHFFFAOYSA-N 0.000 claims description 2
- JVMYDAKCSRHLEK-UHFFFAOYSA-N 3-iodo-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-methylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(C)C(I)=C1 JVMYDAKCSRHLEK-UHFFFAOYSA-N 0.000 claims description 2
- SCIAZBXOVPXAAS-UHFFFAOYSA-N 3-iodo-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(I)=C1 SCIAZBXOVPXAAS-UHFFFAOYSA-N 0.000 claims description 2
- OUTSIUGMFSQICJ-UHFFFAOYSA-N 4-amino-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(N)C=C1 OUTSIUGMFSQICJ-UHFFFAOYSA-N 0.000 claims description 2
- QKLWJACYWLHEAQ-UHFFFAOYSA-N 4-bromo-5-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]thiophene-2-sulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC(Br)=C(Cl)S1 QKLWJACYWLHEAQ-UHFFFAOYSA-N 0.000 claims description 2
- PBXGNYAIGYTWMO-UHFFFAOYSA-N 4-bromo-5-chlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC(Br)=C(Cl)S1 PBXGNYAIGYTWMO-UHFFFAOYSA-N 0.000 claims description 2
- DJYPFUNKOIGNDV-UHFFFAOYSA-N 4-bromo-n-[4-methoxy-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)phenyl]benzenesulfonamide Chemical compound C1=C(C=2CCN(C)CC=2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(Br)C=C1 DJYPFUNKOIGNDV-UHFFFAOYSA-N 0.000 claims description 2
- OZYPUQNRUYTZDI-UHFFFAOYSA-N 4-bromo-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(Br)C=C1 OZYPUQNRUYTZDI-UHFFFAOYSA-N 0.000 claims description 2
- KDWOPRGKLIGEMV-UHFFFAOYSA-N 4-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-nitrobenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 KDWOPRGKLIGEMV-UHFFFAOYSA-N 0.000 claims description 2
- FRASUHRYTBHUSF-UHFFFAOYSA-N 4-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(Cl)C=C1 FRASUHRYTBHUSF-UHFFFAOYSA-N 0.000 claims description 2
- IHSKRXGUPGHJRL-UHFFFAOYSA-N 4-fluoro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=C(F)C=C1 IHSKRXGUPGHJRL-UHFFFAOYSA-N 0.000 claims description 2
- 108091005435 5-HT6 receptors Proteins 0.000 claims description 2
- FKHDVURVQRRQMC-UHFFFAOYSA-N 5-chloro-2-methoxy-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC(Cl)=CC=C1OC FKHDVURVQRRQMC-UHFFFAOYSA-N 0.000 claims description 2
- XIQLIQVRKNMMHE-UHFFFAOYSA-N 5-chloro-3-methyl-n-[3-(4-methylpiperazin-1-yl)-4-propan-2-yloxyphenyl]-1-benzothiophene-2-sulfonamide Chemical compound CC(C)OC1=CC=C(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)C=C1N1CCN(C)CC1 XIQLIQVRKNMMHE-UHFFFAOYSA-N 0.000 claims description 2
- CSXCGXMJPAIVSL-UHFFFAOYSA-N 5-chloro-3-methyl-n-[7-(4-methylpiperazin-1-yl)-2,3-dihydro-1-benzofuran-5-yl]-1-benzothiophene-2-sulfonamide Chemical compound C1CN(C)CCN1C1=CC(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)=CC2=C1OCC2 CSXCGXMJPAIVSL-UHFFFAOYSA-N 0.000 claims description 2
- OPAGNFGYYZRBMY-UHFFFAOYSA-N 5-chloro-n-(4-methoxy-3-piperazin-1-ylphenyl)naphthalene-1-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C=2C3=CC=CC(Cl)=C3C=CC=2)C=C1N1CCNCC1 OPAGNFGYYZRBMY-UHFFFAOYSA-N 0.000 claims description 2
- ZNLVVHRYRJURIX-UHFFFAOYSA-N 5-chloro-n-(4-methoxy-3-piperazin-1-ylphenyl)naphthalene-2-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C=2C=C3C=CC=C(Cl)C3=CC=2)C=C1N1CCNCC1 ZNLVVHRYRJURIX-UHFFFAOYSA-N 0.000 claims description 2
- LNNVCHDELSXIJX-UHFFFAOYSA-N 5-chloro-n-[1-[2-(dimethylamino)ethyl]-2,3-dihydroindol-6-yl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound S1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)NC1=CC=C2CCN(CCN(C)C)C2=C1 LNNVCHDELSXIJX-UHFFFAOYSA-N 0.000 claims description 2
- VMXPBOWBAUBBKW-UHFFFAOYSA-N 5-chloro-n-[3-[4-(cyclopropylmethyl)piperazin-1-yl]-4-methoxyphenyl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)C=C1N(CC1)CCN1CC1CC1 VMXPBOWBAUBBKW-UHFFFAOYSA-N 0.000 claims description 2
- ZINLARKOVIPOJW-UHFFFAOYSA-N 5-chloro-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)C=C1N1CCN(C)CC1 ZINLARKOVIPOJW-UHFFFAOYSA-N 0.000 claims description 2
- LVFWTBJPVUYJFU-UHFFFAOYSA-N 5-iodo-n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-methylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC(I)=CC=C1C LVFWTBJPVUYJFU-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- SFXNPFJCLQYFAX-UHFFFAOYSA-N n-[2-bromo-5-(4-methylpiperazin-1-yl)phenyl]naphthalene-2-sulfonamide Chemical compound C1CN(C)CCN1C1=CC=C(Br)C(NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)=C1 SFXNPFJCLQYFAX-UHFFFAOYSA-N 0.000 claims description 2
- LFCAFAUBHUEPPF-UHFFFAOYSA-N n-[4-bromo-3-(4-methylpiperazin-1-yl)phenyl]naphthalene-2-sulfonamide Chemical compound C1CN(C)CCN1C1=CC(NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)=CC=C1Br LFCAFAUBHUEPPF-UHFFFAOYSA-N 0.000 claims description 2
- ZUAHTVLOPRODJH-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-1-benzofuran-2-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C=2OC3=CC=CC=C3C=2)C=C1N1CCN(C)CC1 ZUAHTVLOPRODJH-UHFFFAOYSA-N 0.000 claims description 2
- SPWDRGXBRZSIHU-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2,1,3-benzothiadiazole-4-sulfonamide Chemical compound COC1=CC=C(NS(=O)(=O)C=2C3=NSN=C3C=CC=2)C=C1N1CCN(C)CC1 SPWDRGXBRZSIHU-UHFFFAOYSA-N 0.000 claims description 2
- BNHPPXTUWQTEEE-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2,3,5,6-tetramethylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=C(C)C(C)=CC(C)=C1C BNHPPXTUWQTEEE-UHFFFAOYSA-N 0.000 claims description 2
- BEPNNIXIAODVKF-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-(trifluoromethyl)benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC=C1C(F)(F)F BEPNNIXIAODVKF-UHFFFAOYSA-N 0.000 claims description 2
- BPLWOIRQKQJYCW-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-(trifluoromethyl)benzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(C(F)(F)F)=C1 BPLWOIRQKQJYCW-UHFFFAOYSA-N 0.000 claims description 2
- ZAUCQVUCRQZMRT-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C1=CC=CC(C)=C1 ZAUCQVUCRQZMRT-UHFFFAOYSA-N 0.000 claims description 2
- XYKOEYVUPFAGKY-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-phenylbenzenesulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C1=CC=CC=C1 XYKOEYVUPFAGKY-UHFFFAOYSA-N 0.000 claims description 2
- ODETWRWNUJHYEY-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-5-pyridin-2-ylthiophene-2-sulfonamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NS(=O)(=O)C(S1)=CC=C1C1=CC=CC=N1 ODETWRWNUJHYEY-UHFFFAOYSA-N 0.000 claims description 2
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- KCRWOXITFISNTG-UHFFFAOYSA-N n-[7-(4-methylpiperazin-1-yl)-2,3-dihydro-1-benzofuran-5-yl]naphthalene-1-sulfonamide Chemical compound C1CN(C)CCN1C1=CC(NS(=O)(=O)C=2C3=CC=CC=C3C=CC=2)=CC2=C1OCC2 KCRWOXITFISNTG-UHFFFAOYSA-N 0.000 description 1
- MNBUYYFUFDJDRM-UHFFFAOYSA-N n-[7-(4-methylpiperazin-1-yl)-2,3-dihydro-1-benzofuran-5-yl]thiophene-2-sulfonamide Chemical compound C1CN(C)CCN1C1=CC(NS(=O)(=O)C=2SC=CC=2)=CC2=C1OCC2 MNBUYYFUFDJDRM-UHFFFAOYSA-N 0.000 description 1
- NSBIQPJIWUJBBX-UHFFFAOYSA-N n-methoxyaniline Chemical compound CONC1=CC=CC=C1 NSBIQPJIWUJBBX-UHFFFAOYSA-N 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000003751 serotonin 6 antagonist Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- BPSUJSDZHLTNJR-UHFFFAOYSA-N sulfamide;hydrochloride Chemical compound Cl.NS(N)(=O)=O BPSUJSDZHLTNJR-UHFFFAOYSA-N 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- FYFXFHWPEFYDKI-UHFFFAOYSA-N tert-butyl 4-(5-amino-2-methoxyphenyl)piperazine-1-carboxylate Chemical compound COC1=CC=C(N)C=C1N1CCN(C(=O)OC(C)(C)C)CC1 FYFXFHWPEFYDKI-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
- C07D261/14—Nitrogen atoms
- C07D261/16—Benzene-sulfonamido isoxazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Pyridine Compounds (AREA)
- Steroid Compounds (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9626377.7A GB9626377D0 (en) | 1996-12-19 | 1996-12-19 | Novel compounds |
| GBGB9700901.3A GB9700901D0 (en) | 1997-01-17 | 1997-01-17 | Novel compounds |
| GB9626377.7 | 1997-10-27 | ||
| GBGB9722757.3A GB9722757D0 (en) | 1997-10-27 | 1997-10-27 | Novel compounds |
| GB9722757.3 | 1997-10-27 | ||
| GB9700901.3 | 1997-10-27 | ||
| PCT/EP1997/007159 WO1998027081A1 (en) | 1996-12-19 | 1997-12-15 | Sulphonamide derivatives, process for their preparation, and their use as medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001506646A true JP2001506646A (ja) | 2001-05-22 |
| JP2001506646A5 JP2001506646A5 (https=) | 2005-08-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52734798A Ceased JP2001506646A (ja) | 1996-12-19 | 1997-12-15 | スルホンアミド誘導体、それらの製造方法、および医薬としてのそれらの使用 |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US6423717B1 (https=) |
| EP (1) | EP0946539B1 (https=) |
| JP (1) | JP2001506646A (https=) |
| KR (1) | KR20000069554A (https=) |
| CN (1) | CN1246116A (https=) |
| AP (1) | AP1277A (https=) |
| AR (1) | AR010795A1 (https=) |
| AT (1) | ATE247099T1 (https=) |
| AU (1) | AU729056B2 (https=) |
| BG (1) | BG103530A (https=) |
| BR (1) | BR9713734A (https=) |
| CA (1) | CA2275492A1 (https=) |
| CZ (1) | CZ220399A3 (https=) |
| DE (1) | DE69724142T2 (https=) |
| DZ (1) | DZ2376A1 (https=) |
| EA (1) | EA002351B1 (https=) |
| ES (1) | ES2203831T3 (https=) |
| HU (1) | HUP0000658A3 (https=) |
| ID (1) | ID22821A (https=) |
| IL (1) | IL130297A0 (https=) |
| MA (1) | MA24426A1 (https=) |
| NO (1) | NO993003L (https=) |
| NZ (1) | NZ335970A (https=) |
| OA (1) | OA11066A (https=) |
| PE (1) | PE46899A1 (https=) |
| PL (1) | PL334337A1 (https=) |
| SK (1) | SK80899A3 (https=) |
| TR (1) | TR199901361T2 (https=) |
| TW (1) | TW418205B (https=) |
| UY (1) | UY24819A1 (https=) |
| WO (1) | WO1998027081A1 (https=) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004536080A (ja) * | 2001-06-11 | 2004-12-02 | ビオヴィトルム・アクチボラゲット | 置換スルホンアミド化合物、cns障害、肥満およびii型糖尿病の処置のための医薬としてのそれらの使用方法 |
| JP2005517705A (ja) * | 2002-02-13 | 2005-06-16 | グラクソ グループ リミテッド | ベンゼンスルホンアミド誘導体ならびにドーパミンd3およびd2受容体リガンドとしてのその使用 |
| JP2005522452A (ja) * | 2002-02-13 | 2005-07-28 | グラクソ グループ リミテッド | Cns疾患の治療のための、5−ht6受容体アフィニティーを有する7−アリールスルホンアミド−2,3,4,5−テトラヒドロ−1h−ベンゾ’ジアゼピン誘導体 |
| JP2005526724A (ja) * | 2002-02-13 | 2005-09-08 | グラクソ グループ リミテッド | 抗精神病剤としてのベンゼンスルホンアミド誘導体 |
| JP2005536551A (ja) * | 2002-06-20 | 2005-12-02 | ビオヴィトルム・アクチボラゲット | 肥満症、ii型糖尿病およびcns障害の治療に有用な新規化合物 |
| JP2006519785A (ja) * | 2003-02-20 | 2006-08-31 | エンサイシブ・ファーマシューティカルズ・インコーポレイテッド | フェニレンジアミンウロテンシン−ii受容体拮抗薬およびccr−9拮抗薬 |
| JP2007514745A (ja) * | 2003-12-19 | 2007-06-07 | ビオヴィトルム・アクチボラゲット | 5−ht6受容体関連疾患の予防または処置に用いられ得る新規ベンゾフラン誘導体 |
| JP2008508221A (ja) * | 2004-07-28 | 2008-03-21 | グラクソ グループ リミテッド | 消化器疾患の治療に有用なピペラジン誘導体 |
| JP2008516918A (ja) * | 2004-10-14 | 2008-05-22 | アボット ゲーエムベーハー ウント カンパニー カーゲー | ドーパミンd3受容体の調節に応答する障害の治療に好適な複素環化合物 |
| JP2009534354A (ja) * | 2006-04-19 | 2009-09-24 | アボット ゲーエムベーハー ウント カンパニー カーゲー | セロトニン5ht6受容体の調節に応答する障害を治療するために好適な複素環アリールスルホン類 |
| JP2010508300A (ja) * | 2006-10-26 | 2010-03-18 | フライン、ギャリー・エー. | アクアポリン修飾因子並びに浮腫および体液平衡異常の治療のためのそれらの使用方法 |
| JP2010515699A (ja) * | 2007-01-10 | 2010-05-13 | エフ.ホフマン−ラ ロシュ アーゲー | キマーゼ阻害剤としてのスルホンアミド誘導体 |
| JP2011502973A (ja) * | 2007-11-02 | 2011-01-27 | アボット ゲーエムベーハー ウント カンパニー カーゲー | セロトニン5−ht6受容体の調節に応答する障害の治療に適するベンゼンスルホンアニリド化合物 |
| JP2011524365A (ja) * | 2008-06-11 | 2011-09-01 | アイアールエム・リミテッド・ライアビリティ・カンパニー | マラリアの処置に有用な化合物および組成物 |
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| DZ2376A1 (fr) * | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
| AU736256B2 (en) * | 1997-07-11 | 2001-07-26 | Smithkline Beecham Plc | Novel compounds |
| CA2318731C (en) | 1998-01-29 | 2012-05-29 | Tularik Inc. | Ppar-gamma modulators |
| GB9803411D0 (en) * | 1998-02-18 | 1998-04-15 | Smithkline Beecham Plc | Novel compounds |
| US6194410B1 (en) * | 1998-03-11 | 2001-02-27 | Hoffman-La Roche Inc. | Pyrazolopyrimidine and pyrazolines and process for preparation thereof |
| GB9810671D0 (en) * | 1998-05-18 | 1998-07-15 | Pfizer Ltd | Anti-pruritic agents |
| GB9818914D0 (en) * | 1998-08-28 | 1998-10-21 | Smithkline Beecham Plc | Use |
| GB9818916D0 (en) | 1998-08-28 | 1998-10-21 | Smithkline Beecham Plc | Use |
| GB9820113D0 (en) | 1998-09-15 | 1998-11-11 | Merck Sharp & Dohme | Therapeutic agents |
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| GB9926302D0 (en) * | 1999-11-05 | 2000-01-12 | Smithkline Beecham Plc | Novel compounds |
| WO2001045694A1 (en) * | 1999-12-21 | 2001-06-28 | Smithkline Beecham Corporation | Urotensin-ii receptor antagonists |
| SE9904723D0 (sv) * | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
| SE0001899D0 (sv) | 2000-05-22 | 2000-05-22 | Pharmacia & Upjohn Ab | New compounds |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| US6818639B2 (en) | 2000-07-21 | 2004-11-16 | Biovitrum Ab | Pharmaceutical combination formulation and method of treatment with the combination |
| SE0002754D0 (sv) * | 2000-07-21 | 2000-07-21 | Pharmacia & Upjohn Ab | New pharmaceutical combination formulation and method of treatment with the combination |
| SE0002739D0 (sv) * | 2000-07-21 | 2000-07-21 | Pharmacia & Upjohn Ab | New use |
| US6399617B1 (en) | 2000-07-21 | 2002-06-04 | Biovitrum Ab | Use |
| AU2001288053A1 (en) * | 2000-09-18 | 2002-03-26 | Toa Eiyo Ltd. | N-substituted benzothiophenesulfonamide derivatives |
| US7071220B2 (en) | 2000-09-18 | 2006-07-04 | Toa Eiyo Ltd. | N-substituted benzothiophenesulfonamide derivatives |
| US7034029B2 (en) | 2000-11-02 | 2006-04-25 | Wyeth | 1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands |
| EP1341783A1 (en) | 2000-11-21 | 2003-09-10 | Smithkline Beecham Plc | Isoquinoline derivatives useful in the treatment of cns disorders |
| KR20030064852A (ko) | 2000-12-22 | 2003-08-02 | 이시하라 산교 가부시끼가이샤 | 아닐린 유도체 또는 그의 염 및 이들을 함유하는사이토카인 생산 억제제 |
| WO2002088101A2 (en) * | 2001-04-27 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of bace |
| EP1385495A4 (en) * | 2001-05-07 | 2005-12-21 | Smithkline Beecham Corp | SULPHONAMIDES |
| JP2004529168A (ja) * | 2001-05-07 | 2004-09-24 | スミスクライン・ビーチャム・コーポレイション | スルホンアミド |
| US6743796B2 (en) * | 2001-05-07 | 2004-06-01 | Wyeth | Piperazinyl-isatins |
| AR033879A1 (es) * | 2001-05-07 | 2004-01-07 | Smithkline Beecham Corp | Compuesto sulfonamida, composicion farmaceutica que lo comprende, su uso para preparar dicha composicion y procedimiento para la obtencion de dicho compuesto |
| JP2004535390A (ja) * | 2001-05-07 | 2004-11-25 | スミスクライン・ビーチャム・コーポレイション | スルホンアミド |
| WO2002089793A1 (en) * | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
| GB0111186D0 (en) * | 2001-05-08 | 2001-06-27 | Smithkline Beecham Plc | Novel compounds |
| US7718650B2 (en) | 2001-05-11 | 2010-05-18 | Biovitrum Ab | Aryl sulfonamide compounds for treating obesity |
| RS88803A (sr) * | 2001-05-11 | 2007-02-05 | Biovitrum Ab., | Nova jedinjenja arilsulfonamida za lečenje gojaznosti, dijabetesa tipa ii i poremećaja cns |
| WO2002092585A1 (en) | 2001-05-11 | 2002-11-21 | Biovitrum Ab | Novel, arylsusfonamide compounds for the treatment of obesity, type ii diabetes and cns-disorders |
| EP1401813B1 (en) | 2001-06-07 | 2007-02-07 | F. Hoffman-la Roche AG | New indole derivatives with 5-ht6 receptor affinity |
| DE60212841T2 (de) | 2001-06-15 | 2007-06-21 | F. Hoffmann-La Roche Ag | 4 piperazinylindolderivate mit affinität zum 5-ht6-rezeptor |
| US6727264B1 (en) * | 2001-07-05 | 2004-04-27 | Synaptic Pharmaceutical Corporation | Substituted anilinic piperidines as MCH selective antagonists |
| WO2003013510A1 (en) * | 2001-08-07 | 2003-02-20 | Smithkline Beecham P.L.C. | 3-arylsulfonyl-7-piperazinyl- indoles, -benzofurans and -benzothiophenes with 5-ht6 receptor affinity for treating cns disorders |
| HRP20040090A2 (en) * | 2001-08-10 | 2004-12-31 | Hoffmann La Roche | Arylsulfonyl derivatives with 5-ht<sub>6</sub> receptor affinity |
| JP4221294B2 (ja) | 2001-09-05 | 2009-02-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 摂食亢進剤および食欲不振症治療剤 |
| SE0103644D0 (sv) * | 2001-11-01 | 2001-11-01 | Astrazeneca Ab | Therapeutic isoquinoline compounds |
| EP1450806B1 (en) * | 2001-11-09 | 2009-04-29 | Biovitrum AB (publ) | Use of sulfonamide derivatives in the treatment of obesity or for the reduction of food intake |
| RS44304A (sr) | 2001-11-22 | 2007-06-04 | Biovitrum Ab., | Inhibitori 11-beta- hidroksistereoidne dehidrogenaze tipa 1 |
| RS44204A (sr) | 2001-11-22 | 2007-06-04 | Biovitrum Ab., | Inhibitori 11-beta- hidroksistereoidne dehidrogenaze tipa 1 |
| CN1321115C (zh) * | 2001-11-30 | 2007-06-13 | 霍夫曼-拉罗奇有限公司 | 作为哮喘治疗中的ccr-3受体拮抗剂的哌嗪衍生物 |
| WO2003066056A1 (en) * | 2002-02-05 | 2003-08-14 | Glaxo Group Limited | Method of promoting neuronal growth |
| AU2003203148A1 (en) * | 2002-02-05 | 2003-09-02 | High Point Pharmaceuticals, Llc | Novel aryl- and heteroarylpiperazines |
| BRPI0308696B8 (pt) | 2002-03-27 | 2021-05-25 | Axovant Sciences Gmbh | composto derivado de quinolina, seu processo de preparação, sua composição farmacêutica e seus usos |
| US20040142948A1 (en) * | 2002-05-07 | 2004-07-22 | Dashyant Dhanak | Sulfonamides |
| HRP20041030B1 (hr) * | 2002-05-13 | 2013-03-31 | F. Hoffmann - La Roche Ag | Derivati benzoksazina kao regulatori 5-ht6 i njihova upotreba |
| EP1513828A1 (en) * | 2002-06-20 | 2005-03-16 | Biovitrum AB | New compounds useful for the treatment of obesity, type ii diabetes and cns disorders |
| EP1897881A3 (en) | 2002-06-20 | 2009-03-18 | Biovitrum AB (publ) | Compounds useful for the treatment of obesity, type II diabetes and CNS disorders |
| PL376479A1 (en) | 2002-10-18 | 2005-12-27 | F.Hoffmann-La Roche Ag | 4-piperazinyl benzenesulfonyl indoles with 5-ht6 receptor affinity |
| AU2003295408A1 (en) * | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| AU2003291262A1 (en) * | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| MXPA05007485A (es) | 2003-01-14 | 2006-01-30 | Arena Pharm Inc | Derivados de arilo y heteroarilo 1,2,3-trisubstituidos como moduladores del metabolismo y la profilaxis y tratamiento de trastornos relacionados con ello tales como diabetes e hiperglicemia. |
| US7153858B2 (en) | 2003-01-31 | 2006-12-26 | Epix Delaware, Inc. | Arylpiperazinyl compounds |
| US20060257613A1 (en) * | 2003-02-13 | 2006-11-16 | Horst Berneth | Metal complexes as light-absorbing compounds in the information layer of optical data carriers |
| TWI289141B (en) | 2003-03-11 | 2007-11-01 | Hoffmann La Roche F. Ag. | Quinolinone derivatives and uses thereof |
| WO2004087654A2 (en) * | 2003-03-31 | 2004-10-14 | Janssen Pharmaceutica N.V. | Phospholipase c inhibitors for use in treating inflammatory disorders |
| US6946466B2 (en) * | 2003-04-10 | 2005-09-20 | Schering Ag | Aromatic sulfonamides as peroxynitrite-rearrangement catalysts |
| US20040204422A1 (en) * | 2003-04-14 | 2004-10-14 | Abbott Gmbh & Co. Kg. | N-[(Piperazinyl)hetaryl]arylsulfonamide compounds |
| PT1558582E (pt) | 2003-07-22 | 2006-05-31 | Arena Pharm Inc | Derivados de diaril- e aril-heteroaril-ureia como moduladores do receptor de serotonina 5-ht2a uteis para a profilaxia e tratamento de desordens relacionadas com o mesmo |
| GB0320320D0 (en) * | 2003-08-29 | 2003-10-01 | Glaxo Group Ltd | Novel compounds |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| BRPI0417833A (pt) * | 2003-12-19 | 2007-04-17 | Biovitrum Ab | novos derivados de benzofurano, os quais podem ser usados na profilaxia ou tratamento de distúrbios relacionados com o receptor 5-ht6 |
| CN102114244A (zh) * | 2004-09-30 | 2011-07-06 | 弗·哈夫曼-拉罗切有限公司 | 治疗认知障碍的组合物和方法 |
| ATE520659T1 (de) | 2004-10-14 | 2011-09-15 | Abbott Gmbh & Co Kg | Zur behandlung von auf die modulation des dopamin-d3-rezeptors ansprechenden erkrankungen geeignete azabicycloheptylverbindungen |
| WO2006062481A1 (en) * | 2004-12-09 | 2006-06-15 | Biovitrum Ab | New benzofuran derivatives and their use in the treatment of obesity, type ii diabetes and cns disorders . |
| EP1676841A1 (en) * | 2004-12-30 | 2006-07-05 | Esteve Laboratorios Dr. Esteve S.A. | Substitited indazolyl sulfonamide and 2,3-dihydro-indolyl sulfonamide compounds, their prepartion and use in medicaments |
| KR100931928B1 (ko) * | 2005-01-12 | 2009-12-15 | 인제대학교 산학협력단 | P25/cdk5 저해 화합물을 포함하는 퇴행성 뇌질환의 예방 및치료용 약학 조성물 |
| RU2499795C2 (ru) | 2005-07-04 | 2013-11-27 | Хай Пойнт Фармасьютикалс, ЛЛС | Антагонисты гистаминовых н3-рецепторов |
| EA013875B1 (ru) | 2005-08-12 | 2010-08-30 | Сувен Лайф Сайенсиз Лимитед | Аминоарильные сульфонамидные производные как функциональные 5-нтлиганды |
| WO2007020654A1 (en) | 2005-08-16 | 2007-02-22 | Suven Life Sciences | An improved process for the preparation of losartan |
| WO2007076875A2 (en) * | 2006-01-06 | 2007-07-12 | Aarhus Universitet | Compounds acting on the serotonin transporter |
| TW200808709A (en) | 2006-03-31 | 2008-02-16 | Glaxo Group Ltd | Novel compounds |
| TW200808762A (en) | 2006-04-19 | 2008-02-16 | Abbott Gmbh & Co Kg | Heterocyclic compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor |
| US8318927B2 (en) | 2006-05-23 | 2012-11-27 | High Point Pharmaceuticals, Llc | 6-(4-cyclopropylpiperazin-1-yl)-2′-methyl-[3, 4′]-bipyridine and its uses as a medicament |
| SG163547A1 (en) | 2006-05-29 | 2010-08-30 | High Point Pharmaceuticals Llc | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
| AU2007343063B2 (en) | 2007-01-08 | 2011-02-17 | Suven Life Sciences Limited | 5-(Heterocyclyl)alkyl-N-(arylsulfonyl)indole compounds and their use as 5-HT6 ligands |
| US8507469B2 (en) | 2007-03-23 | 2013-08-13 | Abbott Gmbh & Co. Kg | Azetidin compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT6 receptor |
| BRPI0809873A2 (pt) | 2007-05-03 | 2018-11-13 | Suven Life Sciences Ltd | "composto, processo para a preparação do composto, método para o tratamento de uma desordem do sistema nervoso central, composição farmacêutica, uso do composto, método para testar antagonistas e antagonistas com seletividade para o receptor 5-th6 e método de tratamento" |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| EP2016943B1 (en) * | 2007-07-19 | 2011-02-23 | Laboratorios del Dr. Esteve S.A. | Substituted tetrahydro-quinoline-sulfonamide compounds, their preparation and use as medicaments |
| CN101835748B (zh) | 2007-10-26 | 2012-11-14 | 苏文生命科学有限公司 | 氨基芳基磺胺化合物及其作为5-ht6配体的用途 |
| EP2508177A1 (en) | 2007-12-12 | 2012-10-10 | Glaxo Group Limited | Combinations comprising 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline |
| WO2009123714A2 (en) | 2008-04-02 | 2009-10-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| WO2009128058A1 (en) | 2008-04-18 | 2009-10-22 | UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al | Psycho-pharmaceuticals |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| WO2010032257A1 (en) | 2008-09-17 | 2010-03-25 | Suven Life Sciences Limited | Aryl indolyl sulfonamide compounds and their use as 5-ht6 ligands |
| EP2346847B1 (en) * | 2008-09-17 | 2013-05-15 | Suven Life Sciences Limited | Aryl sulfonamide amine compounds and their use as 5-ht6 ligands |
| WO2010062321A1 (en) | 2008-10-28 | 2010-06-03 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and crystalline forms related thereto |
| UA100192C2 (en) | 2008-11-11 | 2012-11-26 | УАЙТ ЭлЭлСи | 1-(arylsulfonyl)-4-(piperazin-1-yl)-1h-benzimidazoles as 5-hydroxytryptamine-6 ligands |
| KR101073703B1 (ko) | 2009-04-07 | 2011-10-14 | 한국화학연구원 | 피페라진 유도체, 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 중추신경계 질환의 예방 또는 치료용 약학적 조성물 |
| US8343959B2 (en) | 2009-04-30 | 2013-01-01 | Abbott Gmbh & Co. Kg | N-phenyl-(piperazinyl or homopiperazinyl)-benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT6 receptor |
| MX2011011519A (es) | 2009-04-30 | 2012-01-30 | Abbott Gmbh & Co Kg | Compuestos de bencensulfonanilida adecuados para tratar trastornos que responden a la modulacion del receptor de serotonina 5-ht6. |
| MX2011011520A (es) | 2009-04-30 | 2012-06-19 | Abbott Gmbh & Co Kg | Compuestos de n-fenil-(piperazinil u homopiperazinil)-bencensulfon amida o bencensulfonil-fenil-(piperazina u homopiperazina) adecuados para tratar trastornos que responden a la modulacion del receptor de serotonina 5-ht6. |
| CN102459199A (zh) * | 2009-04-30 | 2012-05-16 | 雅培股份有限两合公司 | 适于治疗响应于5-羟色胺5-ht6受体调节的病症的苯磺酰苯胺化合物 |
| CA2786072C (en) | 2010-01-05 | 2014-10-28 | Suven Life Sciences Limited | Sulfone compounds as 5-ht6 receptor ligands |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012059431A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | Benzenesulfonyl or sulfonamide compounds suitable for treating disorders that respond to the modulation of the serotonin 5-ht6 receptor |
| WO2012059432A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | N-phenyl-(homo)piperazinyl-benzenesulfonyl or benzenesulfonamide compounds suitable for treating disorders that respond to the modulation of the 5-ht6 receptor |
| ES2413911B1 (es) * | 2011-12-15 | 2014-05-14 | Universidad De Zaragoza | Agente inhibidor de la agregación del peptido beta amiloide. |
| CA2866910A1 (en) | 2012-03-20 | 2013-09-26 | Adamed Sp. Z O.O. | Sulphonamide derivatives of benzylamine for the treatment of cns diseases |
| MX394360B (es) | 2013-03-14 | 2025-03-24 | Sumitomo Pharma Oncology Inc | Inhibidores de jak2 y alk2 y metodos para su uso. |
| DK3027613T3 (en) | 2013-07-25 | 2018-06-25 | Univ Jagiellonski | Pyrroloquinoline derivatives as 5-HT6 antagonists, preparation and use thereof |
| WO2015158313A1 (en) | 2014-04-19 | 2015-10-22 | Sunshine Lake Pharma Co., Ltd. | Sulfonamide derivatives and pharmaceutical applications thereof |
| CN105367473B (zh) * | 2014-08-12 | 2020-02-11 | 广东东阳光药业有限公司 | 吲哚啉类衍生物及其在药物上的应用 |
| CN105367472B (zh) * | 2014-08-12 | 2020-04-21 | 广东东阳光药业有限公司 | 吲哚啉类衍生物及其在药物上的应用 |
| MX386419B (es) | 2015-01-06 | 2025-03-18 | Arena Pharm Inc | Metodos de condiciones de tratamiento relacionadas con el receptor s1p1. |
| WO2016201373A1 (en) | 2015-06-12 | 2016-12-15 | Axovant Sciences Ltd. | Diaryl and arylheteroaryl urea derivatives useful for the prophylaxis and treatment of rem sleep behavior disorder |
| EP3939965A1 (en) | 2015-06-22 | 2022-01-19 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid for use in sipi receptor-associated disorders |
| WO2017011767A2 (en) | 2015-07-15 | 2017-01-19 | Axovant Sciences Ltd. | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of hallucinations associated with a neurodegenerative disease |
| CN108926565A (zh) * | 2017-05-26 | 2018-12-04 | 中国科学院上海生命科学研究院 | 五羟色胺受体亚型6小分子激活剂及拮抗剂在防治阿尔茨海默症中的应用 |
| WO2019180176A1 (en) | 2018-03-21 | 2019-09-26 | Spherium Biomed, S.L. | Composition for the treatment of schizophrenia and/or psychosis |
| ES2987794T3 (es) | 2018-06-06 | 2024-11-18 | Arena Pharm Inc | Procedimientos de tratamiento de afecciones relacionadas con el receptor S1P1 |
| MX2021000977A (es) | 2018-07-26 | 2021-04-12 | Sumitomo Pharma Oncology Inc | Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos. |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE81861C (https=) | ||||
| NZ193654A (en) * | 1979-05-16 | 1984-08-24 | Wuelfing Johann A | Naphthalene sulphonamido-alkyl-piperidines,pyrrolidines or piperazines and pharmaceutical compositions |
| US4315014A (en) * | 1980-09-24 | 1982-02-09 | Warner-Lambert Company | Antibacterial amide compounds and pharmaceutical composition containing the same |
| EP0076072B1 (en) * | 1981-09-24 | 1987-05-13 | BEECHAM - WUELFING GmbH & Co. KG | Sulphonamides |
| CN85106905A (zh) * | 1985-08-08 | 1987-02-04 | Fmc公司 | 含有1-芳基-δ2-1,2,4,-三唑啉-5-酮类的除草剂及其制备方法 |
| EP0462179A4 (en) * | 1989-02-27 | 1992-03-18 | The Du Pont Merck Pharmaceutical Company | Novel sulfonamides as radiosensitizers |
| JPH04330057A (ja) * | 1991-05-01 | 1992-11-18 | Hiroyoshi Hidaka | アニリンアリールスルホン酸アミド類及び薬剤として許容され得るその酸付加塩 |
| GB9119932D0 (en) * | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
| DE4206531A1 (de) * | 1992-03-02 | 1993-09-09 | Bayer Ag | N-aryl-stickstoffheterocyclen |
| DE4303376A1 (de) * | 1993-02-05 | 1994-08-11 | Bayer Ag | Substituierte Triazolinone |
| WO1995006637A1 (en) * | 1993-09-03 | 1995-03-09 | Smithkline Beecham Plc | Indole and indoline derivatives as 5ht1d receptor antagonists |
| WO1995011243A1 (en) * | 1993-10-19 | 1995-04-27 | Smithkline Beecham Plc | Benzanilide derivatives as 5ht-1d receptor antagonists |
| EP0733048A1 (en) * | 1993-12-07 | 1996-09-25 | Smithkline Beecham Plc | Heterocyclic biphenylylamides useful as 5ht1d antagonists |
| JPH10500960A (ja) * | 1994-05-28 | 1998-01-27 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5ht1d−アンタゴニスト活性を有するアミド誘導体 |
| US5939451A (en) | 1996-06-28 | 1999-08-17 | Hoffmann-La Roche Inc. | Use of sulfonamides |
| DZ2376A1 (fr) * | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
-
1997
- 1997-12-07 DZ DZ970226A patent/DZ2376A1/xx active
- 1997-12-15 SK SK808-99A patent/SK80899A3/sk unknown
- 1997-12-15 IL IL13029797A patent/IL130297A0/xx unknown
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- 1997-12-15 CA CA002275492A patent/CA2275492A1/en not_active Abandoned
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- 1997-12-15 AP APAP/P/1999/001556A patent/AP1277A/en active
- 1997-12-15 EP EP97954929A patent/EP0946539B1/en not_active Expired - Lifetime
- 1997-12-17 MA MA24902A patent/MA24426A1/fr unknown
- 1997-12-17 AR ARP970105951A patent/AR010795A1/es not_active Application Discontinuation
- 1997-12-17 PE PE1997001126A patent/PE46899A1/es not_active Application Discontinuation
- 1997-12-18 TW TW086119136A patent/TW418205B/zh not_active IP Right Cessation
- 1997-12-18 UY UY24819A patent/UY24819A1/es not_active Application Discontinuation
-
1999
- 1999-06-18 OA OA9900133A patent/OA11066A/en unknown
- 1999-06-18 NO NO993003A patent/NO993003L/no not_active Application Discontinuation
- 1999-06-25 BG BG103530A patent/BG103530A/bg unknown
-
2000
- 2000-08-21 US US09/643,200 patent/US6423717B1/en not_active Expired - Fee Related
-
2002
- 2002-05-29 US US10/157,258 patent/US6599904B2/en not_active Expired - Fee Related
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004536080A (ja) * | 2001-06-11 | 2004-12-02 | ビオヴィトルム・アクチボラゲット | 置換スルホンアミド化合物、cns障害、肥満およびii型糖尿病の処置のための医薬としてのそれらの使用方法 |
| JP2005517705A (ja) * | 2002-02-13 | 2005-06-16 | グラクソ グループ リミテッド | ベンゼンスルホンアミド誘導体ならびにドーパミンd3およびd2受容体リガンドとしてのその使用 |
| JP2005522452A (ja) * | 2002-02-13 | 2005-07-28 | グラクソ グループ リミテッド | Cns疾患の治療のための、5−ht6受容体アフィニティーを有する7−アリールスルホンアミド−2,3,4,5−テトラヒドロ−1h−ベンゾ’ジアゼピン誘導体 |
| JP2005526724A (ja) * | 2002-02-13 | 2005-09-08 | グラクソ グループ リミテッド | 抗精神病剤としてのベンゼンスルホンアミド誘導体 |
| JP4754821B2 (ja) * | 2002-06-20 | 2011-08-24 | プロキシマゲン・リミテッド | 肥満症、ii型糖尿病およびcns障害の治療に有用な新規化合物 |
| JP2005536551A (ja) * | 2002-06-20 | 2005-12-02 | ビオヴィトルム・アクチボラゲット | 肥満症、ii型糖尿病およびcns障害の治療に有用な新規化合物 |
| JP2006519785A (ja) * | 2003-02-20 | 2006-08-31 | エンサイシブ・ファーマシューティカルズ・インコーポレイテッド | フェニレンジアミンウロテンシン−ii受容体拮抗薬およびccr−9拮抗薬 |
| JP2007514745A (ja) * | 2003-12-19 | 2007-06-07 | ビオヴィトルム・アクチボラゲット | 5−ht6受容体関連疾患の予防または処置に用いられ得る新規ベンゾフラン誘導体 |
| JP2008508221A (ja) * | 2004-07-28 | 2008-03-21 | グラクソ グループ リミテッド | 消化器疾患の治療に有用なピペラジン誘導体 |
| JP2008516918A (ja) * | 2004-10-14 | 2008-05-22 | アボット ゲーエムベーハー ウント カンパニー カーゲー | ドーパミンd3受容体の調節に応答する障害の治療に好適な複素環化合物 |
| JP2009534354A (ja) * | 2006-04-19 | 2009-09-24 | アボット ゲーエムベーハー ウント カンパニー カーゲー | セロトニン5ht6受容体の調節に応答する障害を治療するために好適な複素環アリールスルホン類 |
| JP2010508300A (ja) * | 2006-10-26 | 2010-03-18 | フライン、ギャリー・エー. | アクアポリン修飾因子並びに浮腫および体液平衡異常の治療のためのそれらの使用方法 |
| JP2010515699A (ja) * | 2007-01-10 | 2010-05-13 | エフ.ホフマン−ラ ロシュ アーゲー | キマーゼ阻害剤としてのスルホンアミド誘導体 |
| JP2011502973A (ja) * | 2007-11-02 | 2011-01-27 | アボット ゲーエムベーハー ウント カンパニー カーゲー | セロトニン5−ht6受容体の調節に応答する障害の治療に適するベンゼンスルホンアニリド化合物 |
| JP2011524365A (ja) * | 2008-06-11 | 2011-09-01 | アイアールエム・リミテッド・ライアビリティ・カンパニー | マラリアの処置に有用な化合物および組成物 |
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