NO325259B1 - Substituerte N1-(benzensulfonyl) indoler, slike forbindelser for bruk i terapi, anvendelse av slike forbindelser samt farmasoytiske preparat inneholdende nevnte forbindelser. - Google Patents
Substituerte N1-(benzensulfonyl) indoler, slike forbindelser for bruk i terapi, anvendelse av slike forbindelser samt farmasoytiske preparat inneholdende nevnte forbindelser. Download PDFInfo
- Publication number
- NO325259B1 NO325259B1 NO20031589A NO20031589A NO325259B1 NO 325259 B1 NO325259 B1 NO 325259B1 NO 20031589 A NO20031589 A NO 20031589A NO 20031589 A NO20031589 A NO 20031589A NO 325259 B1 NO325259 B1 NO 325259B1
- Authority
- NO
- Norway
- Prior art keywords
- indole
- piperazinyl
- hydrochloride
- phenyl
- sulfonyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 149
- 238000002560 therapeutic procedure Methods 0.000 title claims 2
- VDWLCYCWLIKWBV-UHFFFAOYSA-N 1-(benzenesulfonyl)indole Chemical class C1=CC2=CC=CC=C2N1S(=O)(=O)C1=CC=CC=C1 VDWLCYCWLIKWBV-UHFFFAOYSA-N 0.000 title description 2
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 68
- -1 (2) naphthyl Chemical group 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000004193 piperazinyl group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 108091005435 5-HT6 receptors Proteins 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- YBZUJCJMFCFJSZ-UHFFFAOYSA-N 4-piperazin-1-yl-1-pyridin-3-ylsulfonylindole;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CN=C1 YBZUJCJMFCFJSZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000032544 Cicatrix Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 231100000241 scar Toxicity 0.000 claims description 4
- 230000037387 scars Effects 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 3
- SPADOBCFWOJMAX-UHFFFAOYSA-N 1-(2,4-difluorophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 SPADOBCFWOJMAX-UHFFFAOYSA-N 0.000 claims description 3
- ZSONFEJSWICLKA-UHFFFAOYSA-N 1-(2,4-difluorophenyl)sulfonyl-5-(4-methylpiperazin-1-yl)indole Chemical compound C1CN(C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C(=CC(F)=CC=3)F)C2=C1 ZSONFEJSWICLKA-UHFFFAOYSA-N 0.000 claims description 3
- QHKPPLCPYZAQOQ-UHFFFAOYSA-N 1-(2,5-dimethoxyphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 QHKPPLCPYZAQOQ-UHFFFAOYSA-N 0.000 claims description 3
- LSMUXFVVSTXKNU-UHFFFAOYSA-N 1-(2-methylsulfonylphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 LSMUXFVVSTXKNU-UHFFFAOYSA-N 0.000 claims description 3
- QCEWVKZGAFFFOJ-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-5-(4-methylpiperazin-1-yl)indole Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(C)CC3)C=C2C=C1 QCEWVKZGAFFFOJ-UHFFFAOYSA-N 0.000 claims description 3
- LTCQHJOUSNIUCG-UHFFFAOYSA-N 1-(3-chloro-2-methylphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.CC1=C(Cl)C=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 LTCQHJOUSNIUCG-UHFFFAOYSA-N 0.000 claims description 3
- HHVBKKJQFBDESI-UHFFFAOYSA-N 1-(3-fluorophenyl)sulfonyl-5-(4-propylpiperazin-1-yl)indole Chemical compound C1CN(CCC)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=C(F)C=CC=3)C2=C1 HHVBKKJQFBDESI-UHFFFAOYSA-N 0.000 claims description 3
- UMRXUXYDSUQMEF-UHFFFAOYSA-N 1-(3-fluorophenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound FC1=CC=CC(S(=O)(=O)N2C3=CC=C(C=C3C=C2)N2CCNCC2)=C1 UMRXUXYDSUQMEF-UHFFFAOYSA-N 0.000 claims description 3
- IQJMVQFWIHYBRM-UHFFFAOYSA-N 1-(4-butoxyphenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCNCC3)C=C2C=C1 IQJMVQFWIHYBRM-UHFFFAOYSA-N 0.000 claims description 3
- JCNAHIMZWCCNPC-UHFFFAOYSA-N 1-(4-fluorophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 JCNAHIMZWCCNPC-UHFFFAOYSA-N 0.000 claims description 3
- KAWOWBDBJOLFIT-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 KAWOWBDBJOLFIT-UHFFFAOYSA-N 0.000 claims description 3
- IEFWXRZKTNRMCM-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCNCC3)C=C2C=C1 IEFWXRZKTNRMCM-UHFFFAOYSA-N 0.000 claims description 3
- QKDXOMCVUMIMBW-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonyl-5-(4-methylpiperazin-1-yl)indole Chemical compound C1CN(C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=CC(C)=CC=3)C2=C1 QKDXOMCVUMIMBW-UHFFFAOYSA-N 0.000 claims description 3
- ROXBNUKZHDDLIW-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonyl-5-(4-propan-2-ylpiperazin-1-yl)indole Chemical compound C1CN(C(C)C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=CC(C)=CC=3)C2=C1 ROXBNUKZHDDLIW-UHFFFAOYSA-N 0.000 claims description 3
- DXCQEVKPNDTXBF-UHFFFAOYSA-N 1-(4-phenylphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1C1=CC=CC=C1 DXCQEVKPNDTXBF-UHFFFAOYSA-N 0.000 claims description 3
- GCRXSPZZMIZVFT-UHFFFAOYSA-N 1-(4-phenylphenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound C1=CC2=CC(N3CCNCC3)=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1C1=CC=CC=C1 GCRXSPZZMIZVFT-UHFFFAOYSA-N 0.000 claims description 3
- DUFPVOODAWSKMS-UHFFFAOYSA-N 1-(5-chloro-1,3-dimethylpyrazol-4-yl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.CC1=NN(C)C(Cl)=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 DUFPVOODAWSKMS-UHFFFAOYSA-N 0.000 claims description 3
- XLTWZKMMVHMFFC-UHFFFAOYSA-N 1-(benzenesulfonyl)-2-iodo-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.IC1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 XLTWZKMMVHMFFC-UHFFFAOYSA-N 0.000 claims description 3
- QKMRXAFTDMWFRK-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(1,4-diazepan-1-yl)indole;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 QKMRXAFTDMWFRK-UHFFFAOYSA-N 0.000 claims description 3
- KMTAAPCWBXHPGM-UHFFFAOYSA-N 1-(benzenesulfonyl)-5-(4-methylpiperazin-1-yl)indole Chemical compound C1CN(C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=CC=CC=3)C2=C1 KMTAAPCWBXHPGM-UHFFFAOYSA-N 0.000 claims description 3
- UVAQRCSVMXEMFG-UHFFFAOYSA-N 1-(benzenesulfonyl)-5-(4-propan-2-ylpiperazin-1-yl)indole Chemical compound C1CN(C(C)C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=CC=CC=3)C2=C1 UVAQRCSVMXEMFG-UHFFFAOYSA-N 0.000 claims description 3
- WHUZUSSVPDNFIQ-UHFFFAOYSA-N 1-(benzenesulfonyl)-5-piperazin-1-ylindole Chemical compound C1=CC2=CC(N3CCNCC3)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 WHUZUSSVPDNFIQ-UHFFFAOYSA-N 0.000 claims description 3
- QDXBREOSPADMAU-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonyl-5-piperazin-1-ylindole Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N(C1=CC=2)C=CC1=CC=2N1CCNCC1 QDXBREOSPADMAU-UHFFFAOYSA-N 0.000 claims description 3
- KADIKJPQQGYEID-UHFFFAOYSA-N 2,2,2-trifluoro-1-[7-(4-piperazin-1-ylindol-1-yl)sulfonyl-3,4-dihydro-1h-isoquinolin-2-yl]ethanone;hydrochloride Chemical compound Cl.C1=C2CN(C(=O)C(F)(F)F)CCC2=CC=C1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 KADIKJPQQGYEID-UHFFFAOYSA-N 0.000 claims description 3
- WBBGHIZRJLPRQU-UHFFFAOYSA-N 2-chloro-5-[4-(4-piperazin-1-ylindol-1-yl)sulfonylphenoxy]benzonitrile;hydrochloride Chemical compound Cl.C1=C(C#N)C(Cl)=CC=C1OC1=CC=C(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)C=C1 WBBGHIZRJLPRQU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- YKDDAPCECVIJHB-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]oct-2-en-3-yl)-1-(4-fluorophenyl)sulfonylindole Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=CC=C2C(C=2C3CCN(CC3)C=2)=C1 YKDDAPCECVIJHB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- PZEBFZNJAUOZMN-UHFFFAOYSA-N 4-piperazin-1-yl-1-(2,4,6-trimethylphenyl)sulfonylindole;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(C)=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 PZEBFZNJAUOZMN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- XSGMFWNSTRUFKG-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(4-butoxyphenyl)sulfonylindole Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 XSGMFWNSTRUFKG-UHFFFAOYSA-N 0.000 claims description 3
- VFZVWMPPFXEMTK-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(4-methoxyphenyl)sulfonylindole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 VFZVWMPPFXEMTK-UHFFFAOYSA-N 0.000 claims description 3
- UEPJQQKYGBLQKD-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(4-phenylphenyl)sulfonylindole Chemical compound C1=CC2=CC(N3CCN(CC=4C=CC=CC=4)CC3)=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1C1=CC=CC=C1 UEPJQQKYGBLQKD-UHFFFAOYSA-N 0.000 claims description 3
- CCFWLABVWVAMTD-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(4-propylphenyl)sulfonylindole Chemical compound C1=CC(CCC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 CCFWLABVWVAMTD-UHFFFAOYSA-N 0.000 claims description 3
- OOPIJMKPRBRNLQ-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-naphthalen-2-ylsulfonylindole Chemical compound C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N(C1=CC=2)C=CC1=CC=2N(CC1)CCN1CC1=CC=CC=C1 OOPIJMKPRBRNLQ-UHFFFAOYSA-N 0.000 claims description 3
- IYSCJFMSPDDFSO-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)-1-(4-phenylphenyl)sulfonylindole Chemical compound C1CN(C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=CC(=CC=3)C=3C=CC=CC=3)C2=C1 IYSCJFMSPDDFSO-UHFFFAOYSA-N 0.000 claims description 3
- XNOZLDCDNLLWFB-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)-1-(4-propylphenyl)sulfonylindole Chemical compound C1=CC(CCC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(C)CC3)C=C2C=C1 XNOZLDCDNLLWFB-UHFFFAOYSA-N 0.000 claims description 3
- XFBYJIXGENCVTR-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)-1-naphthalen-1-ylsulfonylindole Chemical compound C1CN(C)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C4=CC=CC=C4C=CC=3)C2=C1 XFBYJIXGENCVTR-UHFFFAOYSA-N 0.000 claims description 3
- WUHULEWMNHLWBC-UHFFFAOYSA-N 5-piperazin-1-yl-1-(4-propylphenyl)sulfonylindole Chemical compound C1=CC(CCC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCNCC3)C=C2C=C1 WUHULEWMNHLWBC-UHFFFAOYSA-N 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- RJTZUHVCZIGJMB-UHFFFAOYSA-N hydron;1h-indole;chloride Chemical compound Cl.C1=CC=C2NC=CC2=C1 RJTZUHVCZIGJMB-UHFFFAOYSA-N 0.000 claims description 3
- TWHUSDMTTVWFJU-UHFFFAOYSA-N 1-(1,1-diphenylethylsulfonyl)-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(S(=O)(=O)N1C2=CC=CC(=C2C=C1)N1CCNCC1)(C)C1=CC=CC=C1 TWHUSDMTTVWFJU-UHFFFAOYSA-N 0.000 claims description 2
- MRYARIHHYCDWLM-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.ClC1=CC=C(Cl)C(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 MRYARIHHYCDWLM-UHFFFAOYSA-N 0.000 claims description 2
- BYPYNAHQJPBQCK-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(3-methylpiperazin-1-yl)indole;hydrochloride Chemical compound Cl.C1CNC(C)CN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C BYPYNAHQJPBQCK-UHFFFAOYSA-N 0.000 claims description 2
- ZHWDJPYNVCXHIP-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(4-methylpiperazin-1-yl)indole;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C ZHWDJPYNVCXHIP-UHFFFAOYSA-N 0.000 claims description 2
- SDWIGEYRDWKNSE-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(4-propan-2-ylpiperazin-1-yl)indole;hydrochloride Chemical compound Cl.C1CN(C(C)C)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C SDWIGEYRDWKNSE-UHFFFAOYSA-N 0.000 claims description 2
- JKYYIRRRAICXNY-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.CC1=CC=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 JKYYIRRRAICXNY-UHFFFAOYSA-N 0.000 claims description 2
- DCHGOAKSFRTTDD-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-5-(4-propylpiperazin-1-yl)indole Chemical compound C1CN(CCC)CCN1C1=CC=C(N(C=C2)S(=O)(=O)C=3C=C(OC)C(OC)=CC=3)C2=C1 DCHGOAKSFRTTDD-UHFFFAOYSA-N 0.000 claims description 2
- VXUNVRFNBGBLCC-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 VXUNVRFNBGBLCC-UHFFFAOYSA-N 0.000 claims description 2
- LNBIHDBWJUYVPO-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 LNBIHDBWJUYVPO-UHFFFAOYSA-N 0.000 claims description 2
- GBRVKJGONYSHJT-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-5-(4-methylpiperazin-1-yl)indole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(C)CC3)C=C2C=C1 GBRVKJGONYSHJT-UHFFFAOYSA-N 0.000 claims description 2
- NTLFABYQKAIIFR-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonyl-4-(4-methylpiperazin-1-yl)indole;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=C(C)C=C1 NTLFABYQKAIIFR-UHFFFAOYSA-N 0.000 claims description 2
- LLCWZXWYBZEIAD-UHFFFAOYSA-N 1-(4-nitrophenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 LLCWZXWYBZEIAD-UHFFFAOYSA-N 0.000 claims description 2
- QEAYVLVFUUDUSS-UHFFFAOYSA-N 1-(4-phenoxyphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 QEAYVLVFUUDUSS-UHFFFAOYSA-N 0.000 claims description 2
- OJQWYDZFQCZYBO-UHFFFAOYSA-N 1-(benzenesulfonyl)-2-phenyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 OJQWYDZFQCZYBO-UHFFFAOYSA-N 0.000 claims description 2
- OXDJHJAYUDYNHW-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(4-ethylpiperazin-1-yl)indole;hydrochloride Chemical compound Cl.C1CN(CC)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 OXDJHJAYUDYNHW-UHFFFAOYSA-N 0.000 claims description 2
- ZCWKDTUDLTZRLM-FAESNJTISA-N 1-(benzenesulfonyl)-4-[(3s,5r)-3,5-dimethylpiperazin-1-yl]indole;hydrochloride Chemical compound Cl.C1[C@@H](C)N[C@@H](C)CN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 ZCWKDTUDLTZRLM-FAESNJTISA-N 0.000 claims description 2
- IQMHVIKDAXHMLN-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 IQMHVIKDAXHMLN-UHFFFAOYSA-N 0.000 claims description 2
- ZVQQLIUIEKAICI-UHFFFAOYSA-N 1-[(4-chlorophenyl)methylsulfonyl]-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1CS(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 ZVQQLIUIEKAICI-UHFFFAOYSA-N 0.000 claims description 2
- RNWASTVGOVZNIP-UHFFFAOYSA-N 1-[(4-methylphenyl)methylsulfonyl]-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1CS(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 RNWASTVGOVZNIP-UHFFFAOYSA-N 0.000 claims description 2
- CDVIJDRERDGJQJ-UHFFFAOYSA-N 1-naphthalen-1-ylsulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 CDVIJDRERDGJQJ-UHFFFAOYSA-N 0.000 claims description 2
- IPONLHAIQBCUCY-UHFFFAOYSA-N 1h-indole;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2NC=CC2=C1 IPONLHAIQBCUCY-UHFFFAOYSA-N 0.000 claims description 2
- QRKRUCCGBQLMDH-UHFFFAOYSA-N 3-(4-piperazin-1-ylindol-1-yl)sulfonylbenzonitrile;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC(C#N)=C1 QRKRUCCGBQLMDH-UHFFFAOYSA-N 0.000 claims description 2
- FUUFZFFAQSIKJV-UHFFFAOYSA-N 4,7-dichloro-4-(4-piperazin-1-ylindol-1-yl)sulfonyl-1h-2,1,3-benzoxadiazole;hydrochloride Chemical compound Cl.C1=CC(Cl)=C2NON=C2C1(Cl)S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 FUUFZFFAQSIKJV-UHFFFAOYSA-N 0.000 claims description 2
- JPPJJSVGIWDPAW-UHFFFAOYSA-N 4-(4-methyl-1,4-diazepan-1-yl)-1-(2-methylphenyl)sulfonylindole;hydrochloride Chemical compound Cl.C1CN(C)CCCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C JPPJJSVGIWDPAW-UHFFFAOYSA-N 0.000 claims description 2
- IMNCPLVIEIOKNT-UHFFFAOYSA-N 4-(4-piperazin-1-ylindol-1-yl)sulfonylbenzonitrile;hydrochloride Chemical compound Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=C(C#N)C=C1 IMNCPLVIEIOKNT-UHFFFAOYSA-N 0.000 claims description 2
- XHEMNSOQGXPJQI-SWSMCDPZSA-N 4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-4-yl]-1-(2-methylphenyl)sulfonylindole;hydrochloride Chemical compound Cl.C1=CC=2C([C@]34N(C)C[C@@](NC3)(C4)[H])=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1C XHEMNSOQGXPJQI-SWSMCDPZSA-N 0.000 claims description 2
- JVPQUSFIBZAZSK-UHFFFAOYSA-N 4-piperazin-1-yl-1-[3-(trifluoromethyl)phenyl]sulfonylindole;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 JVPQUSFIBZAZSK-UHFFFAOYSA-N 0.000 claims description 2
- FXHKZDJQADNARY-UHFFFAOYSA-N 4-piperazin-1-yl-1-[4-(trifluoromethoxy)phenyl]sulfonylindole;hydrochloride Chemical compound Cl.C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 FXHKZDJQADNARY-UHFFFAOYSA-N 0.000 claims description 2
- PLAIMVGNTZJMFL-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(3-fluorophenyl)sulfonylindole Chemical compound FC1=CC=CC(S(=O)(=O)N2C3=CC=C(C=C3C=C2)N2CCN(CC=3C=CC=CC=3)CC2)=C1 PLAIMVGNTZJMFL-UHFFFAOYSA-N 0.000 claims description 2
- UYVJZADTDXWVPU-UHFFFAOYSA-N 5-[1-(2-methylphenyl)sulfonylindol-4-yl]-1,2,3,4,4a,5,6,7-octahydropyrrolo[1,2-b]pyridazine;hydrochloride Chemical compound Cl.CC1=CC=CC=C1S(=O)(=O)N1C2=CC=CC(C3C4CCCNN4CC3)=C2C=C1 UYVJZADTDXWVPU-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- QMQFATGTHCWOHP-UHFFFAOYSA-N n-[[5-(4-piperazin-1-ylindol-1-yl)sulfonylthiophen-2-yl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)NCC(S1)=CC=C1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 QMQFATGTHCWOHP-UHFFFAOYSA-N 0.000 claims description 2
- 229940076279 serotonin Drugs 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- ZOYYQAZDLZMAIN-UHFFFAOYSA-N 1-(2,5-dimethoxyphenyl)sulfonyl-4-piperazin-1-ylindole Chemical compound COC1=CC=C(OC)C(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 ZOYYQAZDLZMAIN-UHFFFAOYSA-N 0.000 claims 1
- RZIQHRZPHXPJHD-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.COC1=CC=C(Br)C=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 RZIQHRZPHXPJHD-UHFFFAOYSA-N 0.000 claims 1
- AAHPXAVXBNZXSU-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)indole;hydrochloride Chemical compound Cl.C1CN(C)CCCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 AAHPXAVXBNZXSU-UHFFFAOYSA-N 0.000 claims 1
- OPAMDWUUNKYGOR-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-piperazin-1-ylindole Chemical compound C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 OPAMDWUUNKYGOR-UHFFFAOYSA-N 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- DRIVXJZAFKUJKG-UHFFFAOYSA-N 4-(4-ethylpiperazin-1-yl)-1-(2-methylphenyl)sulfonylindole;hydrochloride Chemical compound Cl.C1CN(CC)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C DRIVXJZAFKUJKG-UHFFFAOYSA-N 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 104
- 238000000034 method Methods 0.000 description 74
- 238000004128 high performance liquid chromatography Methods 0.000 description 70
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000000460 chlorine Substances 0.000 description 32
- 239000000203 mixture Substances 0.000 description 31
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000000543 intermediate Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- OEAMZRWFIQSVJQ-UHFFFAOYSA-N tert-butyl 4-(1h-indol-4-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC2=C1C=CN2 OEAMZRWFIQSVJQ-UHFFFAOYSA-N 0.000 description 21
- 239000011550 stock solution Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 159000000000 sodium salts Chemical class 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- 150000003840 hydrochlorides Chemical class 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 11
- 229910004298 SiO 2 Inorganic materials 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- DLGYNPROORIVRG-UHFFFAOYSA-N 4-bromo-1-(2-methylphenyl)sulfonylindole Chemical compound CC1=CC=CC=C1S(=O)(=O)N1C2=CC=CC(Br)=C2C=C1 DLGYNPROORIVRG-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000003480 eluent Substances 0.000 description 7
- 235000012631 food intake Nutrition 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- HCVHHKPCZJWQCF-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-bromoindole Chemical compound C1=CC=2C(Br)=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 HCVHHKPCZJWQCF-UHFFFAOYSA-N 0.000 description 4
- 101710150235 5-hydroxytryptamine receptor 6 Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 4
- 229910052804 chromium Inorganic materials 0.000 description 4
- 239000011651 chromium Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000037406 food intake Effects 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- GRJZJFUBQYULKL-UHFFFAOYSA-N 4-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1C=CN2 GRJZJFUBQYULKL-UHFFFAOYSA-N 0.000 description 3
- 229940124801 5-HT6 antagonist Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229910052681 coesite Inorganic materials 0.000 description 3
- 229910052906 cristobalite Inorganic materials 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000003751 serotonin 6 antagonist Substances 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 239000011775 sodium fluoride Substances 0.000 description 3
- 235000013024 sodium fluoride Nutrition 0.000 description 3
- 229910052682 stishovite Inorganic materials 0.000 description 3
- 230000006103 sulfonylation Effects 0.000 description 3
- 238000005694 sulfonylation reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229910052905 tridymite Inorganic materials 0.000 description 3
- SQNJTVRBGMQSBC-UHFFFAOYSA-N (5-bromoindol-1-yl)-tri(propan-2-yl)silane Chemical compound BrC1=CC=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1 SQNJTVRBGMQSBC-UHFFFAOYSA-N 0.000 description 2
- RIKSUZWCYKLNJL-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 RIKSUZWCYKLNJL-UHFFFAOYSA-N 0.000 description 2
- YKTVIJHDSPSXMG-UHFFFAOYSA-N 1-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.S1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 YKTVIJHDSPSXMG-UHFFFAOYSA-N 0.000 description 2
- ZOYUAHDHSGGDBS-UHFFFAOYSA-N 1h-indol-4-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC2=C1C=CN2 ZOYUAHDHSGGDBS-UHFFFAOYSA-N 0.000 description 2
- XPJTUCSESGEMOI-UHFFFAOYSA-N 2-methylsulfonylbenzenesulfonyl chloride Chemical compound CS(=O)(=O)C1=CC=CC=C1S(Cl)(=O)=O XPJTUCSESGEMOI-UHFFFAOYSA-N 0.000 description 2
- GWUYFSCVOUIHJR-UHFFFAOYSA-N 4-(4-ethylpiperazin-1-yl)-1-(2-methylphenyl)sulfonylindole Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C GWUYFSCVOUIHJR-UHFFFAOYSA-N 0.000 description 2
- LNBPBQCQMJPTQS-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-1h-indole Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C=CN2 LNBPBQCQMJPTQS-UHFFFAOYSA-N 0.000 description 2
- OZDCZHDOIBUGAJ-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)C=C1 OZDCZHDOIBUGAJ-UHFFFAOYSA-N 0.000 description 2
- LLUHFMVGGMJDKV-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(3,4-dimethoxyphenyl)sulfonylindole Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 LLUHFMVGGMJDKV-UHFFFAOYSA-N 0.000 description 2
- QCBUZBCDMSMRJZ-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)-1h-indole Chemical compound C1CN(C)CCN1C1=CC=C(NC=C2)C2=C1 QCBUZBCDMSMRJZ-UHFFFAOYSA-N 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 206010013654 Drug abuse Diseases 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 239000012911 assay medium Substances 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000007958 cherry flavor Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 238000010972 statistical evaluation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- LYSHDIRLYBYQKD-UHFFFAOYSA-N tert-butyl 4-[1-(benzenesulfonyl)-2-iodoindol-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC2=C1C=C(I)N2S(=O)(=O)C1=CC=CC=C1 LYSHDIRLYBYQKD-UHFFFAOYSA-N 0.000 description 2
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- UCQCQHLQAXYDSR-UHFFFAOYSA-N (1-tert-butyl-4-chloroindol-2-yl)-trimethylsilane Chemical compound C1=CC=C2N(C(C)(C)C)C([Si](C)(C)C)=CC2=C1Cl UCQCQHLQAXYDSR-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- ZXHMUQVMGJYGAV-UHFFFAOYSA-N (4-bromoindol-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CC=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1Br ZXHMUQVMGJYGAV-UHFFFAOYSA-N 0.000 description 1
- DBJRPJSDYFDWPV-UHFFFAOYSA-N (4-chlorophenyl)methanesulfonyl chloride Chemical compound ClC1=CC=C(CS(Cl)(=O)=O)C=C1 DBJRPJSDYFDWPV-UHFFFAOYSA-N 0.000 description 1
- JALKUHLLMWYIAT-UHFFFAOYSA-N (4-methylphenyl)methanesulfonyl chloride Chemical compound CC1=CC=C(CS(Cl)(=O)=O)C=C1 JALKUHLLMWYIAT-UHFFFAOYSA-N 0.000 description 1
- ONWRSBMOCIQLRK-VOTSOKGWSA-N (e)-2-phenylethenesulfonyl chloride Chemical compound ClS(=O)(=O)\C=C\C1=CC=CC=C1 ONWRSBMOCIQLRK-VOTSOKGWSA-N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- ZXDBIHPLJLMMHR-UHFFFAOYSA-N 1,1-diphenylethanesulfonyl chloride Chemical compound C=1C=CC=CC=1C(S(Cl)(=O)=O)(C)C1=CC=CC=C1 ZXDBIHPLJLMMHR-UHFFFAOYSA-N 0.000 description 1
- UEICVKROHBNAFJ-UHFFFAOYSA-N 1-(1,1-diphenylethylsulfonyl)-4-piperazin-1-ylindole Chemical compound C=1C=CC=CC=1C(S(=O)(=O)N1C2=CC=CC(=C2C=C1)N1CCNCC1)(C)C1=CC=CC=C1 UEICVKROHBNAFJ-UHFFFAOYSA-N 0.000 description 1
- NYANDIQPRAITCC-UHFFFAOYSA-N 1-(1-methylimidazol-4-yl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.CN1C=NC(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 NYANDIQPRAITCC-UHFFFAOYSA-N 0.000 description 1
- WKIOGKRWXUIDGB-UHFFFAOYSA-N 1-(2,4-difluorophenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCNCC3)C=C2C=C1 WKIOGKRWXUIDGB-UHFFFAOYSA-N 0.000 description 1
- JTLWAXBYQXIIMR-UHFFFAOYSA-N 1-(2,5-dichlorothiophen-3-yl)sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.S1C(Cl)=CC(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1Cl JTLWAXBYQXIIMR-UHFFFAOYSA-N 0.000 description 1
- FBLWCALBGOREMV-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(3-methylpiperazin-1-yl)indole Chemical compound C1CNC(C)CN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C FBLWCALBGOREMV-UHFFFAOYSA-N 0.000 description 1
- ASKLWYPALIHLAI-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(4-methylpiperazin-1-yl)indole Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C ASKLWYPALIHLAI-UHFFFAOYSA-N 0.000 description 1
- FFCUFDHXCXEBRC-UHFFFAOYSA-N 1-(2-methylphenyl)sulfonyl-4-(4-propan-2-ylpiperazin-1-yl)indole Chemical compound C1CN(C(C)C)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1C FFCUFDHXCXEBRC-UHFFFAOYSA-N 0.000 description 1
- FQPHBXYROUHKBY-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-5-piperazin-1-ylindole Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCNCC3)C=C2C=C1 FQPHBXYROUHKBY-UHFFFAOYSA-N 0.000 description 1
- MSRIYFDZDOEYAR-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-piperazin-1-ylindole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 MSRIYFDZDOEYAR-UHFFFAOYSA-N 0.000 description 1
- YZLGTPMOVHYENN-UHFFFAOYSA-N 1-(4-nitrophenyl)sulfonyl-4-piperazin-1-ylindole Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 YZLGTPMOVHYENN-UHFFFAOYSA-N 0.000 description 1
- URRVTIMNPCNDLE-UHFFFAOYSA-N 1-(4-phenoxyphenyl)sulfonyl-4-piperazin-1-ylindole Chemical compound C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 URRVTIMNPCNDLE-UHFFFAOYSA-N 0.000 description 1
- LRFBIOVZFRXOAK-UHFFFAOYSA-N 1-(benzenesulfonyl)-2-phenyl-4-piperazin-1-ylindole;tert-butyl 4-[1-(benzenesulfonyl)-2-phenylindol-4-yl]piperazine-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1.C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC2=C1C=C(C=1C=CC=CC=1)N2S(=O)(=O)C1=CC=CC=C1 LRFBIOVZFRXOAK-UHFFFAOYSA-N 0.000 description 1
- YNDHBTJAJJDWLC-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(4-ethylpiperazin-1-yl)indole Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 YNDHBTJAJJDWLC-UHFFFAOYSA-N 0.000 description 1
- SSLMOTKYUJGGEV-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)indole Chemical compound C1CN(C)CCCN1C1=CC=CC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 SSLMOTKYUJGGEV-UHFFFAOYSA-N 0.000 description 1
- FXZXSWUIPQHGMN-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-piperazin-1-ylindole;dihydrochloride Chemical compound Cl.Cl.C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC=C1 FXZXSWUIPQHGMN-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- QLXJICCDNZELOD-UHFFFAOYSA-N 1-[(4-chlorophenyl)methylsulfonyl]-4-piperazin-1-ylindole Chemical compound C1=CC(Cl)=CC=C1CS(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 QLXJICCDNZELOD-UHFFFAOYSA-N 0.000 description 1
- TYMDOJMIXGPPRR-UHFFFAOYSA-N 1-[(4-methylphenyl)methylsulfonyl]-4-piperazin-1-ylindole Chemical compound C1=CC(C)=CC=C1CS(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 TYMDOJMIXGPPRR-UHFFFAOYSA-N 0.000 description 1
- JQIPBIAZSTYCQS-UHFFFAOYSA-N 1-[2-methoxy-3-[2-methoxy-5-methyl-3-(4-piperazin-1-ylindol-1-yl)sulfonylphenoxy]-5-methylphenyl]sulfonyl-4-piperazin-1-ylindole;hydrochloride Chemical compound Cl.C1=C(C)C=C(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)C(OC)=C1OC(C=1OC)=CC(C)=CC=1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 JQIPBIAZSTYCQS-UHFFFAOYSA-N 0.000 description 1
- JPRIJTAKNZZJQD-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]sulfonylindole Chemical compound FC(C1=CC=C(C=C1)S(=O)(=O)N1C=CC2=CC=CC=C12)(F)F JPRIJTAKNZZJQD-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
- FJSAJUXIHJIAMD-UHFFFAOYSA-N 2,4-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(F)=C1 FJSAJUXIHJIAMD-UHFFFAOYSA-N 0.000 description 1
- GOPUHTXVZGIOHN-UHFFFAOYSA-N 2,4-dihydroxybenzohydrazide Chemical compound NNC(=O)C1=CC=C(O)C=C1O GOPUHTXVZGIOHN-UHFFFAOYSA-N 0.000 description 1
- BXCOSWRSIISQSL-UHFFFAOYSA-N 2,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(Cl)C(S(Cl)(=O)=O)=C1 BXCOSWRSIISQSL-UHFFFAOYSA-N 0.000 description 1
- JJKSHSHZJOWSEC-UHFFFAOYSA-N 2,5-dichlorothiophene-3-sulfonyl chloride Chemical compound ClC1=CC(S(Cl)(=O)=O)=C(Cl)S1 JJKSHSHZJOWSEC-UHFFFAOYSA-N 0.000 description 1
- YZLKDJCGVHQZEE-UHFFFAOYSA-N 2-(2,2,2-trifluoroacetyl)-3,4-dihydro-1h-isoquinoline-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(Cl)(=O)=O)N(C(=O)C(F)(F)F)CCC2=C1 YZLKDJCGVHQZEE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BJYNYQGJTZULJI-UHFFFAOYSA-N 2-methoxy-5-methylbenzenesulfonyl chloride Chemical compound COC1=CC=C(C)C=C1S(Cl)(=O)=O BJYNYQGJTZULJI-UHFFFAOYSA-N 0.000 description 1
- XBVSGEGNQZAQPM-UHFFFAOYSA-N 2-methyl-1h-indol-4-ol Chemical compound C1=CC=C2NC(C)=CC2=C1O XBVSGEGNQZAQPM-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- RSJSYCZYQNJQPY-UHFFFAOYSA-N 3,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OC RSJSYCZYQNJQPY-UHFFFAOYSA-N 0.000 description 1
- ZWEONBLHFJZSON-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]oct-2-en-3-yl)-1h-indole Chemical compound C1=CC=C2C(C=3C4CCN(C=3)CC4)=CNC2=C1 ZWEONBLHFJZSON-UHFFFAOYSA-N 0.000 description 1
- JZGTVKBDBSZKIY-UHFFFAOYSA-N 3-(4-piperazin-1-ylindol-1-yl)sulfonylbenzonitrile Chemical compound C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=CC(C#N)=C1 JZGTVKBDBSZKIY-UHFFFAOYSA-N 0.000 description 1
- ONCAZCNPWWQQMW-UHFFFAOYSA-N 3-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=CC(S(Cl)(=O)=O)=C1 ONCAZCNPWWQQMW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UFESGJFEJHJCON-UHFFFAOYSA-N 3-chloro-2-methoxybenzenesulfonyl chloride Chemical compound COC1=C(Cl)C=CC=C1S(Cl)(=O)=O UFESGJFEJHJCON-UHFFFAOYSA-N 0.000 description 1
- HGEDKUFVQGCLLO-UHFFFAOYSA-N 4,7-dichloro-4-(4-piperazin-1-ylindol-1-yl)sulfonyl-1h-2,1,3-benzoxadiazole Chemical compound C1=CC(Cl)=C2NON=C2C1(Cl)S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 HGEDKUFVQGCLLO-UHFFFAOYSA-N 0.000 description 1
- VSIYPBHKOVLDIS-UHFFFAOYSA-N 4-(4-piperazin-1-ylindol-1-yl)sulfonylbenzonitrile Chemical compound C1=CC2=C(N3CCNCC3)C=CC=C2N1S(=O)(=O)C1=CC=C(C#N)C=C1 VSIYPBHKOVLDIS-UHFFFAOYSA-N 0.000 description 1
- UHCDBMIOLNKDHG-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenesulfonyl chloride Chemical compound FC(F)(F)OC1=CC=C(S(Cl)(=O)=O)C=C1 UHCDBMIOLNKDHG-UHFFFAOYSA-N 0.000 description 1
- ZNRNXFDKPWNDJY-HRAATJIYSA-N 4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-4-yl]-1-(2-methylphenyl)sulfonylindole Chemical compound C1=CC=2C([C@]34N(C)C[C@@](NC3)(C4)[H])=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1C ZNRNXFDKPWNDJY-HRAATJIYSA-N 0.000 description 1
- KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 1
- SVLZRCRXNHITBY-UHFFFAOYSA-N 4-chloro-1h-indole Chemical compound ClC1=CC=CC2=C1C=CN2 SVLZRCRXNHITBY-UHFFFAOYSA-N 0.000 description 1
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
- DBMFYTQPPBBKHI-UHFFFAOYSA-N 4-cyanobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(C#N)C=C1 DBMFYTQPPBBKHI-UHFFFAOYSA-N 0.000 description 1
- BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 1
- NLMQHXUGJIAKTH-UHFFFAOYSA-N 4-hydroxyindole Chemical compound OC1=CC=CC2=C1C=CN2 NLMQHXUGJIAKTH-UHFFFAOYSA-N 0.000 description 1
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- ALBQXDHCMLLQMB-UHFFFAOYSA-N 4-phenylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1=CC=CC=C1 ALBQXDHCMLLQMB-UHFFFAOYSA-N 0.000 description 1
- NKBGGNTWGYTHCK-UHFFFAOYSA-N 4-piperazin-1-yl-1-(4-propoxyphenyl)sulfonylindole;hydrochloride Chemical compound Cl.C1=CC(OCCC)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 NKBGGNTWGYTHCK-UHFFFAOYSA-N 0.000 description 1
- QSGJWZFLXRWIEL-UHFFFAOYSA-N 4-piperazin-1-yl-1-[3-(trifluoromethyl)phenyl]sulfonylindole Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)N2C3=CC=CC(=C3C=C2)N2CCNCC2)=C1 QSGJWZFLXRWIEL-UHFFFAOYSA-N 0.000 description 1
- UDLMHEREVJFTSO-UHFFFAOYSA-N 4-piperazin-1-yl-1-[4-(trifluoromethoxy)phenyl]sulfonylindole Chemical compound C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)N1C2=CC=CC(N3CCNCC3)=C2C=C1 UDLMHEREVJFTSO-UHFFFAOYSA-N 0.000 description 1
- LHYZGURMLPSRFU-UHFFFAOYSA-N 4-propoxybenzenesulfonyl chloride Chemical compound CCCOC1=CC=C(S(Cl)(=O)=O)C=C1 LHYZGURMLPSRFU-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- YMCJWDYAWULDAZ-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(2,4-difluorophenyl)sulfonylindole Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 YMCJWDYAWULDAZ-UHFFFAOYSA-N 0.000 description 1
- AYCROKQFNPOIGK-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1-(4-methoxyphenyl)sulfonylindole;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC=C(N3CCN(CC=4C=CC=CC=4)CC3)C=C2C=C1 AYCROKQFNPOIGK-UHFFFAOYSA-N 0.000 description 1
- VXYWJJSDQVTFNY-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-1h-indole Chemical compound C1CN(C=2C=C3C=CNC3=CC=2)CCN1CC1=CC=CC=C1 VXYWJJSDQVTFNY-UHFFFAOYSA-N 0.000 description 1
- WVDGJWKVEJAEHX-UHFFFAOYSA-N 5-(4-propan-2-ylpiperazin-1-yl)-1h-indole Chemical compound C1CN(C(C)C)CCN1C1=CC=C(NC=C2)C2=C1 WVDGJWKVEJAEHX-UHFFFAOYSA-N 0.000 description 1
- SSPCWOHYHONVGJ-UHFFFAOYSA-N 5-(4-propylpiperazin-1-yl)-1h-indole Chemical compound C1CN(CCC)CCN1C1=CC=C(NC=C2)C2=C1 SSPCWOHYHONVGJ-UHFFFAOYSA-N 0.000 description 1
- VGSWVDWOXYTAPG-UHFFFAOYSA-N 5-(benzamidomethyl)thiophene-2-sulfonyl chloride Chemical compound S1C(S(=O)(=O)Cl)=CC=C1CNC(=O)C1=CC=CC=C1 VGSWVDWOXYTAPG-UHFFFAOYSA-N 0.000 description 1
- FXLWWIIXYMGVRL-UHFFFAOYSA-N 5-[1-(2-methylphenyl)sulfonylindol-4-yl]-1,2,3,4,4a,5,6,7-octahydropyrrolo[1,2-b]pyridazine Chemical compound CC1=CC=CC=C1S(=O)(=O)N1C2=CC=CC(C3C4CCCNN4CC3)=C2C=C1 FXLWWIIXYMGVRL-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- HWGVUNSKAPCFNF-UHFFFAOYSA-N 5-chloro-1,3-dimethylpyrazole-4-sulfonyl chloride Chemical compound CC1=NN(C)C(Cl)=C1S(Cl)(=O)=O HWGVUNSKAPCFNF-UHFFFAOYSA-N 0.000 description 1
- JLTUANWNGKWRQO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonyl chloride Chemical compound C1=C(Cl)C=C2C(C)=C(S(Cl)(=O)=O)SC2=C1 JLTUANWNGKWRQO-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000964051 Homo sapiens 5-hydroxytryptamine receptor 6 Proteins 0.000 description 1
- 238000001282 Kruskal–Wallis one-way analysis of variance Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000018526 Narcotic-Related disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- JPGQOUSTVILISH-UHFFFAOYSA-N enflurane Chemical compound FC(F)OC(F)(F)C(F)Cl JPGQOUSTVILISH-UHFFFAOYSA-N 0.000 description 1
- 229960000305 enflurane Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- QUXHCILOWRXCEO-UHFFFAOYSA-M magnesium;butane;chloride Chemical compound [Mg+2].[Cl-].CCC[CH2-] QUXHCILOWRXCEO-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- PBOWVMYNPLGHON-UHFFFAOYSA-N n,n-dimethyl-5-(4-piperazin-1-ylindol-1-yl)sulfonylnaphthalen-1-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 PBOWVMYNPLGHON-UHFFFAOYSA-N 0.000 description 1
- GZTPBHHDYMJJEA-UHFFFAOYSA-N n-[[5-(4-piperazin-1-ylindol-1-yl)sulfonylthiophen-2-yl]methyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NCC(S1)=CC=C1S(=O)(=O)N(C1=CC=C2)C=CC1=C2N1CCNCC1 GZTPBHHDYMJJEA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 208000019180 nutritional disease Diseases 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- JIDRDOSAKUEXPQ-UHFFFAOYSA-N tert-butyl 4-(1h-indol-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC2=CC=CC=C2N1 JIDRDOSAKUEXPQ-UHFFFAOYSA-N 0.000 description 1
- PDPSXASABIORPX-UHFFFAOYSA-N tert-butyl-(4-chloroindol-1-yl)-dimethylsilane Chemical compound C1=CC=C2N([Si](C)(C)C(C)(C)C)C=CC2=C1Cl PDPSXASABIORPX-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0003810A SE0003810D0 (sv) | 2000-10-20 | 2000-10-20 | Novel compounds their use and preparations |
US24311500P | 2000-10-25 | 2000-10-25 | |
PCT/SE2001/002319 WO2002032863A1 (en) | 2000-10-20 | 2001-10-19 | 2-, 3-, 4-, or 5-substituted-n1-(benzensulfonyl)indoles and their use in therapy |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20031589D0 NO20031589D0 (no) | 2003-04-08 |
NO20031589L NO20031589L (no) | 2003-05-28 |
NO325259B1 true NO325259B1 (no) | 2008-03-17 |
Family
ID=26655269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20031589A NO325259B1 (no) | 2000-10-20 | 2003-04-08 | Substituerte N1-(benzensulfonyl) indoler, slike forbindelser for bruk i terapi, anvendelse av slike forbindelser samt farmasoytiske preparat inneholdende nevnte forbindelser. |
Country Status (14)
Country | Link |
---|---|
US (2) | US7087750B2 (de) |
EP (1) | EP1326830A1 (de) |
KR (1) | KR100823908B1 (de) |
AU (2) | AU2001296193B2 (de) |
BR (1) | BR0114552A (de) |
CA (1) | CA2422717A1 (de) |
EA (1) | EA006132B1 (de) |
HK (1) | HK1084109A1 (de) |
IL (1) | IL154685A0 (de) |
MX (1) | MXPA03003397A (de) |
NO (1) | NO325259B1 (de) |
NZ (1) | NZ524675A (de) |
PL (1) | PL361887A1 (de) |
WO (1) | WO2002032863A1 (de) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2001296193B2 (en) | 2000-10-20 | 2006-04-27 | Biovitrum Ab | 2-, 3-, 4-, or 5-substituted-N1-(benzensulfonyl)indoles and their use in therapy |
US7034029B2 (en) | 2000-11-02 | 2006-04-25 | Wyeth | 1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands |
CN1222511C (zh) * | 2000-11-02 | 2005-10-12 | 惠氏公司 | 作为5-羟色胺-6配体的1-芳基-或1-烷基磺酰基-杂环基吲哚 |
AU2002220715A1 (en) * | 2000-11-24 | 2002-06-03 | Smithkline Beecham Plc | Indolsulfonyl compounds useful in the treatment of cns disorders |
DE60119982T2 (de) * | 2000-12-22 | 2006-12-21 | Wyeth | Heterozyklylalkylindole oder -azaindole als 5-hydroxytryptamine-6 liganden |
JP4731114B2 (ja) | 2001-06-11 | 2011-07-20 | プロキシマゲン・リミテッド | 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 |
KR20040010709A (ko) * | 2001-06-15 | 2004-01-31 | 에프. 호프만-라 로슈 아게 | 5-ht6 수용체 친화력을 갖는 4-피페라지닐인돌 유도체 |
EP1414442A1 (de) * | 2001-08-07 | 2004-05-06 | Smithkline Beecham Plc | 3-arylsulfonyl-7-piperazinyl-indole, -benzofurane und -benzothiophene mit 5-ht6-rezeptor-affinität für die behandlung von erkrankungen des zentralen nervensystems |
WO2003057698A2 (en) * | 2001-12-28 | 2003-07-17 | Acadia Pharmaceuticals, Inc. | Spiroazacyclic compounds as monoamine receptor modulators |
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 |
WO2003101987A1 (en) * | 2002-05-30 | 2003-12-11 | Neurosearch A/S | 3-substituted quinuclidines and their use |
WO2003104193A1 (en) * | 2002-06-05 | 2003-12-18 | F. Hoffmann-La Roche Ag | 1-sulfonyl-4-aminoalkoxy indole derivatives as 5-ht6-receptor modulators for the treatment of cns-disorders |
WO2004000828A1 (en) * | 2002-06-20 | 2003-12-31 | Biovitrum Ab | New compounds useful for the treatment of obesity, type ii diabetes and cns disorders |
US7943639B2 (en) | 2002-06-20 | 2011-05-17 | Proximagen Limited | Compounds |
BR0314363A (pt) | 2002-09-17 | 2005-07-19 | Hoffmann La Roche | Indóis 2,4-substituìdos e seu uso como moduladores de 5-ht6 |
PL376479A1 (en) * | 2002-10-18 | 2005-12-27 | F.Hoffmann-La Roche Ag | 4-piperazinyl benzenesulfonyl indoles with 5-ht6 receptor affinity |
CA2509982C (en) * | 2002-11-28 | 2011-11-08 | Suven Life Sciences Limited | N-arylsulfonyl-3-substituted indoles having serotonin receptor affinity, process for their preparation and pharmaceutical composition containing them |
BRPI0407493A (pt) * | 2003-02-14 | 2006-02-14 | Wyeth Corp | derivados heterociclil-3-sulfinilazaindol ou -azaindazol como ligantes de 5-hidroxitriptamina-6 |
WO2004108671A1 (en) * | 2003-06-06 | 2004-12-16 | Suven Life Sciences Limited | Substituted indoles with serotonin receptor affinity, process for their preparation and pharmaceutical compositions containing them |
WO2005012254A1 (en) | 2003-07-22 | 2005-02-10 | Arena Pharmaceuticals, Inc. | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related therto |
SE0302760D0 (sv) * | 2003-10-20 | 2003-10-20 | Biovitrum Ab | New compounds |
TW200522944A (en) * | 2003-12-23 | 2005-07-16 | Lilly Co Eli | CB1 modulator compounds |
CA2637531A1 (en) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-ht6 receptor affinity |
BRPI0712898A2 (pt) | 2006-07-03 | 2013-01-08 | Biovitrum Ab | indàis como moduladores de 5-ht6 |
CA2679346A1 (en) | 2007-03-13 | 2008-09-18 | Biovitrum Ab (Publ) | Tricyclic isoquinoline derivatives for treatment of obesity |
US20100041672A1 (en) * | 2007-03-21 | 2010-02-18 | Glaxo Group Limited | Use of quinoline derivatives in the treatment of pain and irritable bowel syndrome |
US20080318941A1 (en) * | 2007-05-24 | 2008-12-25 | Memory Pharmaceuticals Corporation | 4' substituted compounds having 5-ht6 receptor affinity |
AU2008286760A1 (en) * | 2007-08-15 | 2009-02-19 | Memory Pharmaceuticals Corporation | 3' substituted compounds having 5-HT6 receptor affinity |
EP2508177A1 (de) | 2007-12-12 | 2012-10-10 | Glaxo Group Limited | Kombinationen mit 3-phenylsulfonyl-8-piperazinyl-1yl-chinolin |
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 |
US20100016297A1 (en) * | 2008-06-24 | 2010-01-21 | Memory Pharmaceuticals Corporation | Alkyl-substituted 3' compounds having 5-ht6 receptor affinity |
US20100022581A1 (en) * | 2008-07-02 | 2010-01-28 | Memory Pharmaceuticals Corporation | Pyrrolidine-substituted azaindole compounds having 5-ht6 receptor affinity |
US20100029629A1 (en) * | 2008-07-25 | 2010-02-04 | Memory Pharmaceuticals Corporation | Acyclic compounds having 5-ht6 receptor affinity |
US20100056531A1 (en) * | 2008-08-22 | 2010-03-04 | Memory Pharmaceuticals Corporation | Alkyl-substituted 3' compounds having 5-ht6 receptor affinity |
US9126946B2 (en) | 2008-10-28 | 2015-09-08 | 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 |
WO2011088836A1 (en) | 2010-01-25 | 2011-07-28 | H. Lundbeck A/S | NOVEL 4-(ARYL-4-SULFONYL)-6,6a,7,8,9,10-HEXAHYDRO-4H-4,8,10a-TRIAZA-ACEPHENANTHRYLENE AND 3-ARYLSULFONYL-6,6a,7,8,9,10-HEXAHYDRO-3H-3,8,10a-TRIAZA-CYCLOPENTA[C]FLUORENE DERIVATIVES AS SEROTONIN 5-HT6 LIGANDS |
AR080374A1 (es) | 2010-03-05 | 2012-04-04 | Sanofi Aventis | Procedimiento para la preparcion de 2-(ciclohexilmetil)-n-(2-((2s)-1-metilpirrolidin-2-il) etil)- 1,2,3,4-tetrahidroisoquinolin-7- sulfonamida |
PL395469A1 (pl) | 2011-06-29 | 2013-01-07 | Adamed Spólka Z Ograniczona Odpowiedzialnoscia | Pochodne indoloamin do leczenia chorób osrodkowego ukladu nerwowego |
WO2015090233A1 (en) | 2013-12-20 | 2015-06-25 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic compounds and their application in pharmaceuticals |
AU2015286049B2 (en) | 2014-07-08 | 2018-03-01 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic derivatives and pharmaceutical applications thereof |
US10010527B2 (en) * | 2014-08-16 | 2018-07-03 | Suven Sciences Limited | Active metabolite of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate and dimesylate dihydrate salt of active metabolite |
MX2017016413A (es) | 2015-06-12 | 2018-08-01 | Axovant Sciences Gmbh | Derivados de diaril y arilheteroaril urea como moduladores del receptor 5ht2a de serotonina útiles para la profilaxis y el tratamineto de un trastorno conductual del sueño rem. |
MX2018000465A (es) | 2015-07-15 | 2018-09-17 | Axovant Sciences Gmbh | Derivados de diaril y arilheteroaril urea como moduladores del receptor de serotonina 5-ht2a útiles para la profilaxis y el tratamiento de alucinaciones asociadas con una enfermedad neurodegenerativa. |
WO2017052394A1 (en) | 2015-09-23 | 2017-03-30 | Uniwersytet Jagielloński | Imidazopyridine compounds and their use as 5-ht6 receptor ligands |
TWI748194B (zh) | 2018-06-28 | 2021-12-01 | 德商菲尼克斯 Fxr有限責任公司 | 含有雙環核心部分之新穎lxr調節劑 |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW263508B (de) * | 1991-02-12 | 1995-11-21 | Pfizer | |
JPH04273857A (ja) * | 1991-02-26 | 1992-09-30 | Taisho Pharmaceut Co Ltd | N−置換フェニルスルホニルインドール誘導体 |
JPH04321671A (ja) * | 1991-04-17 | 1992-11-11 | Mitsubishi Petrochem Co Ltd | カルバモイルトリアゾール誘導体およびそれを有効成分とする除草剤 |
TW263504B (de) * | 1991-10-03 | 1995-11-21 | Pfizer | |
EP0773942A1 (de) | 1994-07-26 | 1997-05-21 | Pfizer Inc. | 4-indolderivate als serotonin agonisten und antagonisten |
IT1282797B1 (it) * | 1995-04-21 | 1998-03-31 | Colla Paolo | Pirril-(indolil)-aril-sulfoni e relativo processo di produzione ed impiego nella terapia delle infezioni da virus dell'aids |
AU5772196A (en) * | 1995-05-19 | 1996-11-29 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
WO1997046224A1 (en) * | 1996-06-06 | 1997-12-11 | Bifodan A/S | Enteric coating, comprising alginic acid, for an oral preparation |
US5846982A (en) * | 1996-06-14 | 1998-12-08 | Eli Lilly And Company | Inhibition of serotonin reuptake |
JP3421350B2 (ja) * | 1996-07-19 | 2003-06-30 | テュラリク インコーポレイテッド | ペンタフルオロベンゼンスルホンアミドおよび類縁体 |
JPH10298011A (ja) * | 1997-04-30 | 1998-11-10 | Nippon Soda Co Ltd | ピリジルインドール化合物および農園芸用殺菌剤 |
US6296876B1 (en) * | 1997-10-06 | 2001-10-02 | Isa Odidi | Pharmaceutical formulations for acid labile substances |
DE59807829D1 (de) | 1997-10-14 | 2003-05-15 | Lonza Ag | Zweikernige Iridium(I)-phosphinkomplexe und ihre Verwendung als Katalysator in der asymmetrischen Hydroaminierung von Olefinen |
US6100291A (en) * | 1998-03-16 | 2000-08-08 | Allelix Biopharmaceuticals Inc. | Pyrrolidine-indole compounds having 5-HT6 affinity |
US6133287A (en) * | 1998-03-24 | 2000-10-17 | Allelix Biopharmaceuticals Inc. | Piperidine-indole compounds having 5-HT6 affinity |
US6251893B1 (en) * | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
AU4819099A (en) * | 1998-06-19 | 2000-01-05 | Eli Lilly And Company | Inhibition of serotonin reuptake |
ATE319683T1 (de) | 1998-12-11 | 2006-03-15 | Univ Virginia Commonwealth | Selektive 5-ht 6-rezeptor-liganden |
SK287296B6 (sk) * | 2000-02-16 | 2010-06-07 | Smithkline Beecham Plc | Pyrimidín-4-ónové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
PT1294358E (pt) * | 2000-06-28 | 2004-12-31 | Smithkline Beecham Plc | Processo de moagem por via humida |
US6818639B2 (en) * | 2000-07-21 | 2004-11-16 | Biovitrum Ab | Pharmaceutical combination formulation and method of treatment with the combination |
AU2001296193B2 (en) | 2000-10-20 | 2006-04-27 | Biovitrum Ab | 2-, 3-, 4-, or 5-substituted-N1-(benzensulfonyl)indoles and their use in therapy |
CN1222511C (zh) | 2000-11-02 | 2005-10-12 | 惠氏公司 | 作为5-羟色胺-6配体的1-芳基-或1-烷基磺酰基-杂环基吲哚 |
US7034029B2 (en) * | 2000-11-02 | 2006-04-25 | Wyeth | 1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands |
JP2004517826A (ja) * | 2000-11-21 | 2004-06-17 | 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 | Cns障害の治療において有用なイソキノリン誘導体 |
AU2002220715A1 (en) | 2000-11-24 | 2002-06-03 | Smithkline Beecham Plc | Indolsulfonyl compounds useful in the treatment of cns disorders |
US6951823B2 (en) * | 2001-05-14 | 2005-10-04 | Axcelis Technologies, Inc. | Plasma ashing process |
US6630406B2 (en) * | 2001-05-14 | 2003-10-07 | Axcelis Technologies | Plasma ashing process |
KR20040010709A (ko) * | 2001-06-15 | 2004-01-31 | 에프. 호프만-라 로슈 아게 | 5-ht6 수용체 친화력을 갖는 4-피페라지닐인돌 유도체 |
US7279353B2 (en) * | 2003-04-02 | 2007-10-09 | Micron Technology, Inc. | Passivation planarization |
SE0302760D0 (sv) * | 2003-10-20 | 2003-10-20 | Biovitrum Ab | New compounds |
-
2001
- 2001-10-19 AU AU2001296193A patent/AU2001296193B2/en not_active Ceased
- 2001-10-19 KR KR1020037005482A patent/KR100823908B1/ko not_active IP Right Cessation
- 2001-10-19 IL IL15468501A patent/IL154685A0/xx unknown
- 2001-10-19 PL PL36188701A patent/PL361887A1/xx unknown
- 2001-10-19 AU AU9619301A patent/AU9619301A/xx active Pending
- 2001-10-19 EP EP01977043A patent/EP1326830A1/de not_active Withdrawn
- 2001-10-19 WO PCT/SE2001/002319 patent/WO2002032863A1/en active IP Right Grant
- 2001-10-19 BR BR0114552-5A patent/BR0114552A/pt not_active IP Right Cessation
- 2001-10-19 EA EA200300492A patent/EA006132B1/ru not_active IP Right Cessation
- 2001-10-19 NZ NZ524675A patent/NZ524675A/en unknown
- 2001-10-19 MX MXPA03003397A patent/MXPA03003397A/es active IP Right Grant
- 2001-10-19 CA CA002422717A patent/CA2422717A1/en not_active Abandoned
- 2001-10-22 US US10/037,110 patent/US7087750B2/en not_active Expired - Fee Related
-
2003
- 2003-04-08 NO NO20031589A patent/NO325259B1/no not_active IP Right Cessation
-
2005
- 2005-02-11 US US11/057,033 patent/US7524839B2/en not_active Expired - Fee Related
-
2006
- 2006-04-11 HK HK06104346.7A patent/HK1084109A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
BR0114552A (pt) | 2003-07-01 |
KR20030038825A (ko) | 2003-05-16 |
WO2002032863A1 (en) | 2002-04-25 |
CA2422717A1 (en) | 2002-04-25 |
EA006132B1 (ru) | 2005-10-27 |
AU9619301A (en) | 2002-04-29 |
HK1084109A1 (en) | 2006-07-21 |
US20050256106A1 (en) | 2005-11-17 |
NO20031589L (no) | 2003-05-28 |
KR100823908B1 (ko) | 2008-04-21 |
US20020165251A1 (en) | 2002-11-07 |
NO20031589D0 (no) | 2003-04-08 |
MXPA03003397A (es) | 2004-06-30 |
EP1326830A1 (de) | 2003-07-16 |
PL361887A1 (en) | 2004-10-04 |
US7524839B2 (en) | 2009-04-28 |
EA200300492A1 (ru) | 2003-10-30 |
IL154685A0 (en) | 2003-09-17 |
US7087750B2 (en) | 2006-08-08 |
AU2001296193B2 (en) | 2006-04-27 |
NZ524675A (en) | 2004-09-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO325259B1 (no) | Substituerte N1-(benzensulfonyl) indoler, slike forbindelser for bruk i terapi, anvendelse av slike forbindelser samt farmasoytiske preparat inneholdende nevnte forbindelser. | |
AU2001296193A1 (en) | 2-, 3-, 4-, or 5-substituted-N1-(benzensulfonyl)indoles and their use in therapy | |
US7319097B2 (en) | Compounds | |
JP2009185031A (ja) | 2−、3−、4−、または5−置換−n1−(ベンゼンスルホニル)インドールおよび治療におけるそれらの使用 | |
AU2002303061A1 (en) | Novel, arylsulfonamide compounds for the treatment of obesity, type II diabetes and CNS-disorders | |
CZ20033529A3 (cs) | Nové deriváty indolu s afinitou k receptoru 5-HT6 | |
NZ529032A (en) | Substituted sulfonamide compounds, process for their use as medicament for the treatment of CNS disorders, obesity and type II diabetes | |
IE65339B1 (en) | Novel indole derivatives | |
AU2006226162A1 (en) | Arylsulfonyl benzofused heterocycles as 5-HT2A antagonists | |
US20090170824A1 (en) | Diarylsulfones as 5-HT2A Antagonists | |
NO860319L (no) | Fremgangsmaate for fremstillig av terapeutisk aktive 4h-1-benzopyran-4-on-derivater og deres svovelholdige analoger. | |
JP5297386B2 (ja) | 5−アルキルオキシ−インドリン−2−オン誘導体、これらの調製およびv2バソプレシン受容体の選択的リガンドとしての治療におけるこれらの応用 | |
RU2814103C1 (ru) | Новое соединение, способ его получения и его применение | |
KR100922486B1 (ko) | 비만, 제 ⅱ 형 당뇨병 및 cns 장애의 치료를 위한신규한 아릴술폰아미드 화합물 | |
US20080096873A1 (en) | New compounds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |