NO316693B1 - Nye indanolforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem - Google Patents
Nye indanolforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem Download PDFInfo
- Publication number
- NO316693B1 NO316693B1 NO19984620A NO984620A NO316693B1 NO 316693 B1 NO316693 B1 NO 316693B1 NO 19984620 A NO19984620 A NO 19984620A NO 984620 A NO984620 A NO 984620A NO 316693 B1 NO316693 B1 NO 316693B1
- Authority
- NO
- Norway
- Prior art keywords
- trans
- dihydro
- benzodioxin
- formula
- compounds
- Prior art date
Links
- YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical class C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 230000036407 pain Effects 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 92
- -1 methylenedioxy group Chemical group 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 13
- 238000000926 separation method Methods 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 150000001414 amino alcohols Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- BFXGASGIXHYIDV-UYAOXDASSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1[C@H]1[C@H](O)C2=CC=CC=C2C1 BFXGASGIXHYIDV-UYAOXDASSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- YNZCMLKESCNHNS-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-3,6-dihydro-2h-pyridin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)=CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 YNZCMLKESCNHNS-TZIWHRDSSA-N 0.000 claims description 2
- NGAGLDAKVNKYJX-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-6-methoxy-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1[C@@H]1CC2=CC=C(OC)C=C2[C@H]1O NGAGLDAKVNKYJX-TZIWHRDSSA-N 0.000 claims description 2
- HIBLMFFZKNBKME-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-1-yl]-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)CCN1[C@H]1[C@H](O)C2=CC=CC=C2C1 HIBLMFFZKNBKME-TZIWHRDSSA-N 0.000 claims description 2
- ZASQMEFCWNRHSQ-IFMALSPDSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-1-yl]-5-methyl-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(C)C=C2C1 ZASQMEFCWNRHSQ-IFMALSPDSA-N 0.000 claims description 2
- FIMQQCSPXAMCSD-IFMALSPDSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-1-yl]-6-methyl-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)CCN1[C@@H]1CC2=CC=C(C)C=C2[C@H]1O FIMQQCSPXAMCSD-IFMALSPDSA-N 0.000 claims description 2
- SXTSCSDLHDMAOP-NHCUHLMSSA-N (1r,2r)-2-[4-(2,3-dihydro-1-benzofuran-7-yl)piperidin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CN([C@H]2[C@@H](C3=CC=C(F)C=C3C2)O)CCC1C1=CC=CC2=C1OCC2 SXTSCSDLHDMAOP-NHCUHLMSSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims 2
- HVYKQLWDJZYOQY-UYAOXDASSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 HVYKQLWDJZYOQY-UYAOXDASSA-N 0.000 claims 1
- GMBUBVLUQFAQMU-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-5-methoxy-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(OC)C=C2C1 GMBUBVLUQFAQMU-TZIWHRDSSA-N 0.000 claims 1
- OYAFLVNFRTYRSK-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 OYAFLVNFRTYRSK-TZIWHRDSSA-N 0.000 claims 1
- HNIFACCWWKONLS-TZIWHRDSSA-N (1r,2r)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-1-yl]-6-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound O1CCOC2=C1C=CC=C2C(CC1)CCN1[C@H]1[C@H](O)C2=CC(F)=CC=C2C1 HNIFACCWWKONLS-TZIWHRDSSA-N 0.000 claims 1
- XPECPZHOOOLPDY-NHCUHLMSSA-N (1r,2r)-2-[4-(3,4-dihydro-2h-chromen-8-yl)piperazin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CCOC2=C1C=CC=C2N(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 XPECPZHOOOLPDY-NHCUHLMSSA-N 0.000 claims 1
- RDPRQQOVVMNYFR-FGZHOGPDSA-N (1r,2r)-2-[4-(3,4-dihydro-2h-thiochromen-8-yl)-3,6-dihydro-2h-pyridin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CCSC2=C1C=CC=C2C(CC1)=CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 RDPRQQOVVMNYFR-FGZHOGPDSA-N 0.000 claims 1
- CNUDKIHAKDLGRP-UYAOXDASSA-N 4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-[(1r,2r)-5-fluoro-1-hydroxy-2,3-dihydro-1h-inden-2-yl]piperidin-4-ol Chemical compound O1CCOC2=C1C=CC=C2C(O)(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 CNUDKIHAKDLGRP-UYAOXDASSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- KAQJERBONUSJEE-UHFFFAOYSA-N 1-piperidin-1-yl-2,3-dihydroinden-1-ol Chemical class C1CC2=CC=CC=C2C1(O)N1CCCCC1 KAQJERBONUSJEE-UHFFFAOYSA-N 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000003302 alkenyloxy group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 125000005133 alkynyloxy group Chemical group 0.000 abstract 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 abstract 1
- 208000015114 central nervous system disease Diseases 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004193 piperazinyl group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 230000008018 melting Effects 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 241000700159 Rattus Species 0.000 description 11
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- UXVCSPSWUNMPMT-UHFFFAOYSA-N 2-bromo-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C(Br)CC2=C1 UXVCSPSWUNMPMT-UHFFFAOYSA-N 0.000 description 6
- ZMHPIXWPOUTWTA-UHFFFAOYSA-N 2-bromo-5-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C2C(=O)C(Br)CC2=C1 ZMHPIXWPOUTWTA-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000001242 postsynaptic effect Effects 0.000 description 6
- UJGDLLGKMWVCPT-UHFFFAOYSA-N 6-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2CCC(=O)C2=C1 UJGDLLGKMWVCPT-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- NGOZRIZXELGVHK-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1,4-benzodioxine Chemical compound O1CCOC2=C1C=CC=C2Br NGOZRIZXELGVHK-UHFFFAOYSA-N 0.000 description 4
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 230000003518 presynaptic effect Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229960001289 prazosin Drugs 0.000 description 3
- 239000000952 serotonin receptor agonist Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 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
- QOPRWBRNMPANKN-UHFFFAOYSA-N 5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)CCC2=C1 QOPRWBRNMPANKN-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010575 fractional recrystallization Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- YZLUVLPNLMYVEU-NHCUHLMSSA-N (1r,2r)-2-[4-(1-benzofuran-7-yl)piperidin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CN([C@H]2[C@@H](C3=CC=C(F)C=C3C2)O)CCC1C1=CC=CC2=C1OC=C2 YZLUVLPNLMYVEU-NHCUHLMSSA-N 0.000 description 1
- GKUAKOFNTDHSTE-FGZHOGPDSA-N (1r,2r)-2-[4-(3,4-dihydro-2h-chromen-8-yl)-3,6-dihydro-2h-pyridin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CCOC2=C1C=CC=C2C(CC1)=CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 GKUAKOFNTDHSTE-FGZHOGPDSA-N 0.000 description 1
- PPPYBCSUNHZWSN-FGZHOGPDSA-N (1r,2r)-2-[4-(3,4-dihydro-2h-chromen-8-yl)piperidin-1-yl]-5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1CCOC2=C1C=CC=C2C(CC1)CCN1[C@H]1[C@H](O)C2=CC=C(F)C=C2C1 PPPYBCSUNHZWSN-FGZHOGPDSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- CLUQBFWLZUDCNN-UHFFFAOYSA-N 2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-6-methoxy-2,3-dihydroinden-1-one Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1C1CC2=CC=C(OC)C=C2C1=O CLUQBFWLZUDCNN-UHFFFAOYSA-N 0.000 description 1
- HDBQQYKAAQUUEC-UHFFFAOYSA-M 2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)pyridin-1-ium-1-yl]-2,3-dihydroinden-1-one;bromide Chemical compound [Br-].O1CCOC2=C1C=CC=C2C(C=C1)=CC=[N+]1C1C(=O)C2=CC=CC=C2C1 HDBQQYKAAQUUEC-UHFFFAOYSA-M 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- QCVSGRGIMSGRLE-UHFFFAOYSA-N 2-bromo-5,6-difluoro-2,3-dihydroinden-1-one Chemical compound C1=C(F)C(F)=CC2=C1C(=O)C(Br)C2 QCVSGRGIMSGRLE-UHFFFAOYSA-N 0.000 description 1
- LUUMIYKKTVTWOO-UHFFFAOYSA-N 2-bromo-5-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC=C2C(=O)C(Br)CC2=C1 LUUMIYKKTVTWOO-UHFFFAOYSA-N 0.000 description 1
- XXLMNINSVUQJMX-UHFFFAOYSA-N 2-bromo-6-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C2CC(Br)C(=O)C2=C1 XXLMNINSVUQJMX-UHFFFAOYSA-N 0.000 description 1
- VTTUAPDDJQOXBO-UHFFFAOYSA-N 2-bromo-6-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2CC(Br)C(=O)C2=C1 VTTUAPDDJQOXBO-UHFFFAOYSA-N 0.000 description 1
- NHDCLCZJTVWDPI-UHFFFAOYSA-N 2-bromo-6-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC=C2CC(Br)C(=O)C2=C1 NHDCLCZJTVWDPI-UHFFFAOYSA-N 0.000 description 1
- AOJPPAMOVSBASK-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromen-8-yl trifluoromethanesulfonate Chemical compound C1CCSC2=C1C=CC=C2OS(=O)(=O)C(F)(F)F AOJPPAMOVSBASK-UHFFFAOYSA-N 0.000 description 1
- GVGGLXHEJXEOSM-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperidin-4-ol Chemical compound C=1C=CC=2OCCOC=2C=1C1(O)CCNCC1 GVGGLXHEJXEOSM-UHFFFAOYSA-N 0.000 description 1
- HNAJYNJEGJBJPE-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-5-yl)pyridine Chemical compound O1CCOC2=C1C=CC=C2C1=CC=NC=C1 HNAJYNJEGJBJPE-UHFFFAOYSA-N 0.000 description 1
- FFJGCSVJFOTPEO-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound FC1=CC=C2C(O)CCC2=C1 FFJGCSVJFOTPEO-UHFFFAOYSA-N 0.000 description 1
- WVPPBVAMKNQXJA-UHFFFAOYSA-N 5-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C2C(=O)CCC2=C1 WVPPBVAMKNQXJA-UHFFFAOYSA-N 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- PFFIQOPSGRRQFP-UHFFFAOYSA-N 6-bromo-5,6-dihydrocyclopenta[f][1,3]benzodioxol-7-one Chemical compound C1=C2C(=O)C(Br)CC2=CC2=C1OCO2 PFFIQOPSGRRQFP-UHFFFAOYSA-N 0.000 description 1
- CLUAHEPQMQFYFJ-UHFFFAOYSA-N 6-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound C1=C(F)C=C2C(O)CCC2=C1 CLUAHEPQMQFYFJ-UHFFFAOYSA-N 0.000 description 1
- GPZPQJITKRSVQJ-UHFFFAOYSA-N 7-bromo-1-benzofuran Chemical compound BrC1=CC=CC2=C1OC=C2 GPZPQJITKRSVQJ-UHFFFAOYSA-N 0.000 description 1
- VGOUXHRZQNPOPY-UHFFFAOYSA-N 7-bromo-2,3-dihydro-1-benzofuran Chemical compound BrC1=CC=CC2=C1OCC2 VGOUXHRZQNPOPY-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 101000822895 Homo sapiens 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- SBPRIAGPYFYCRT-UHFFFAOYSA-N N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCN(C(=O)C2CCCCC2)C=2N=CC=CC=2)CC1 SBPRIAGPYFYCRT-UHFFFAOYSA-N 0.000 description 1
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- LRLPMKLRAJIMNA-UHFFFAOYSA-N diethyl(pyridin-4-yl)borane Chemical compound CCB(CC)C1=CC=NC=C1 LRLPMKLRAJIMNA-UHFFFAOYSA-N 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- WVLHGCRWEHCIOT-UHFFFAOYSA-N eltoprazine Chemical compound C1CNCCN1C1=CC=CC2=C1OCCO2 WVLHGCRWEHCIOT-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229960001779 pargyline Drugs 0.000 description 1
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
- 229960001999 phentolamine Drugs 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- XXSLZJZUSYNITM-UHFFFAOYSA-N tetrabutylammonium tribromide Chemical compound Br[Br-]Br.CCCC[N+](CCCC)(CCCC)CCCC XXSLZJZUSYNITM-UHFFFAOYSA-N 0.000 description 1
- SFLXUZPXEWWQNH-UHFFFAOYSA-K tetrabutylazanium;tribromide Chemical compound [Br-].[Br-].[Br-].CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC SFLXUZPXEWWQNH-UHFFFAOYSA-K 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9712336A FR2769312B1 (fr) | 1997-10-03 | 1997-10-03 | Nouveaux composes de l'indanol, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO984620D0 NO984620D0 (no) | 1998-10-02 |
| NO984620L NO984620L (no) | 1999-04-06 |
| NO316693B1 true NO316693B1 (no) | 2004-03-26 |
Family
ID=9511782
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19984620A NO316693B1 (no) | 1997-10-03 | 1998-10-02 | Nye indanolforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5958927A (xx) |
| EP (1) | EP0906912B1 (xx) |
| JP (1) | JP3884177B2 (xx) |
| CN (1) | CN1122666C (xx) |
| AT (1) | ATE230739T1 (xx) |
| AU (1) | AU736710B2 (xx) |
| BR (1) | BR9804485A (xx) |
| CA (1) | CA2249756C (xx) |
| DE (1) | DE69810560T2 (xx) |
| DK (1) | DK0906912T3 (xx) |
| ES (1) | ES2190574T3 (xx) |
| FR (1) | FR2769312B1 (xx) |
| HK (1) | HK1019736A1 (xx) |
| HU (1) | HUP9802194A1 (xx) |
| NO (1) | NO316693B1 (xx) |
| NZ (1) | NZ332142A (xx) |
| PL (1) | PL191091B1 (xx) |
| PT (1) | PT906912E (xx) |
| ZA (1) | ZA989011B (xx) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2769312B1 (fr) * | 1997-10-03 | 1999-12-03 | Adir | Nouveaux composes de l'indanol, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2336117A1 (en) * | 1998-06-30 | 2000-01-06 | Sidney Xi Liang | Piperidine derivatives having effects on serotonin related systems |
| US6197798B1 (en) | 1998-07-21 | 2001-03-06 | Novartis Ag | Amino-benzocycloalkane derivatives |
| US6878707B2 (en) * | 2000-01-18 | 2005-04-12 | Novartis Ag | Carboxamides useful as inhibitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion |
| US20020077278A1 (en) * | 2000-06-05 | 2002-06-20 | Yong V. Wee | Use of glatiramer acetate (copolymer 1) in the treatment of central nervous system disorders |
| ATE424825T1 (de) | 2001-07-20 | 2009-03-15 | Psychogenics Inc | Behandlung von hyperaktivitätsstörungen und aufmerksamkeitsdefiziten |
| DE10142662B4 (de) | 2001-08-31 | 2004-07-08 | Aventis Pharma Deutschland Gmbh | Derivate von C2-substituierten Indan-1-ol-Systemen und ihre Verwendung als Arzneimittel |
| DE10142667B4 (de) * | 2001-08-31 | 2004-06-09 | Aventis Pharma Deutschland Gmbh | C2-substituierte Indan-1-ole und ihre Derivate und ihre Verwendung als Arzneimittel |
| DE10142661B4 (de) * | 2001-08-31 | 2004-06-09 | Aventis Pharma Deutschland Gmbh | Mehrfach substituierte Indan-1-ol-Systeme und ihre Verwendung als Arzneimittel |
| FR2883876B1 (fr) * | 2005-03-30 | 2007-05-04 | Servier Lab | Derives d'indanyl-piperazines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0190472B1 (en) * | 1984-12-21 | 1989-07-12 | Duphar International Research B.V | New pharmaceutical compositions having anti-psychotic properties |
| JPH01503777A (ja) * | 1985-10-04 | 1989-12-21 | マツジヨ‐ニ‐ウインスロツプ・ソチエタ・ペル・アチオニ | 縮合脂環式アミノアルコール類 |
| FR2670491B1 (fr) * | 1990-12-14 | 1993-02-05 | Adir | Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| FR2692264B1 (fr) * | 1992-06-12 | 1994-08-05 | Adir | Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les contenant. |
| FR2734819B1 (fr) * | 1995-05-31 | 1997-07-04 | Adir | Nouveaux composes de la piperazine, de la piperidine et de la 1,2,5,6-tetrahydropyridine, leur procede de preparation et les compositions pharmaceutiques les contenant |
| FR2769312B1 (fr) * | 1997-10-03 | 1999-12-03 | Adir | Nouveaux composes de l'indanol, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
-
1997
- 1997-10-03 FR FR9712336A patent/FR2769312B1/fr not_active Expired - Fee Related
-
1998
- 1998-09-30 CN CN98120594A patent/CN1122666C/zh not_active Expired - Fee Related
- 1998-10-01 ES ES98402415T patent/ES2190574T3/es not_active Expired - Lifetime
- 1998-10-01 DK DK98402415T patent/DK0906912T3/da active
- 1998-10-01 EP EP98402415A patent/EP0906912B1/fr not_active Expired - Lifetime
- 1998-10-01 AT AT98402415T patent/ATE230739T1/de not_active IP Right Cessation
- 1998-10-01 DE DE69810560T patent/DE69810560T2/de not_active Expired - Fee Related
- 1998-10-01 CA CA002249756A patent/CA2249756C/fr not_active Expired - Fee Related
- 1998-10-01 PT PT98402415T patent/PT906912E/pt unknown
- 1998-10-02 PL PL328989A patent/PL191091B1/pl not_active IP Right Cessation
- 1998-10-02 AU AU87875/98A patent/AU736710B2/en not_active Ceased
- 1998-10-02 NZ NZ332142A patent/NZ332142A/xx unknown
- 1998-10-02 JP JP28063998A patent/JP3884177B2/ja not_active Expired - Fee Related
- 1998-10-02 ZA ZA989011A patent/ZA989011B/xx unknown
- 1998-10-02 HU HU9802194A patent/HUP9802194A1/hu unknown
- 1998-10-02 US US09/165,844 patent/US5958927A/en not_active Expired - Fee Related
- 1998-10-02 NO NO19984620A patent/NO316693B1/no unknown
- 1998-10-05 BR BR9804485-0A patent/BR9804485A/pt not_active Application Discontinuation
-
1999
- 1999-03-22 US US09/273,889 patent/US6060487A/en not_active Expired - Fee Related
- 1999-10-28 HK HK99104866A patent/HK1019736A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP9802194A1 (hu) | 1999-12-28 |
| NZ332142A (en) | 2000-05-26 |
| CN1122666C (zh) | 2003-10-01 |
| EP0906912B1 (fr) | 2003-01-08 |
| HK1019736A1 (en) | 2000-02-25 |
| PL191091B1 (pl) | 2006-03-31 |
| AU8787598A (en) | 1999-04-22 |
| HU9802194D0 (en) | 1998-11-30 |
| FR2769312A1 (fr) | 1999-04-09 |
| EP0906912A1 (fr) | 1999-04-07 |
| BR9804485A (pt) | 2000-04-11 |
| ATE230739T1 (de) | 2003-01-15 |
| PT906912E (pt) | 2003-04-30 |
| NO984620D0 (no) | 1998-10-02 |
| DE69810560D1 (de) | 2003-02-13 |
| NO984620L (no) | 1999-04-06 |
| AU736710B2 (en) | 2001-08-02 |
| ES2190574T3 (es) | 2003-08-01 |
| PL328989A1 (en) | 1999-04-12 |
| CA2249756C (fr) | 2003-12-02 |
| US6060487A (en) | 2000-05-09 |
| DE69810560T2 (de) | 2003-11-27 |
| JPH11158179A (ja) | 1999-06-15 |
| CN1218051A (zh) | 1999-06-02 |
| ZA989011B (en) | 1999-04-12 |
| CA2249756A1 (fr) | 1999-04-03 |
| US5958927A (en) | 1999-09-28 |
| FR2769312B1 (fr) | 1999-12-03 |
| DK0906912T3 (da) | 2003-04-22 |
| JP3884177B2 (ja) | 2007-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5965575A (en) | N-aryl piperidine compounds as 5HT1B antagonists | |
| DE60009663T2 (de) | Piperidin-, tetrahydropyridin- und piperazin-derivate, ihre herstellung und anwendung | |
| JP4150161B2 (ja) | 置換されたクロマン誘導体 | |
| CN104995191A (zh) | 三环喹啉和喹喔啉衍生物 | |
| JP2000506883A (ja) | 置換１，２，３，４―テトラヒドロナフタレン誘導体 | |
| US5665722A (en) | Benzofuran derivatives as D4 receptor antagonists | |
| US5852019A (en) | Pyrimidinylpyrazole derivatives | |
| NO316693B1 (no) | Nye indanolforbindelser, fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende dem | |
| US5968954A (en) | 2-aminoindan compounds as 5HT1B antagonists | |
| JPH0225481A (ja) | ２―［（４―ピペリジニル）メチル］―１，２，３，４―テトラヒドロイソキノリン誘導体、その製造方法およびその治療への適用 | |
| CA2300302A1 (en) | 8-substituted-9h-1,3-dioxolo/4,5-h//2,3/benzodiazepine derivatives, as ampa/kainate receptor inhibitors | |
| US5096900A (en) | (4-piperidyl)methyl-2,3-dihydro-1h-isoindole and -2,3,4,5-tetrahydro-1h-benzazepine derivatives, their preparation and their application in therapy | |
| JP2000072748A (ja) | 新規なインダン―１―オ―ル化合物、それらの製造方法及びそれらを含有する医薬組成物 | |
| US5081128A (en) | 2,3-dihydro-1h-isoindole derivatives and their application in therapy | |
| JPH037280A (ja) | 新規ベンゾチオピラニルアミン | |
| SK10222001A3 (sk) | Morfolinobenzamidové soli | |
| HU226059B1 (en) | Novel disubstituted trans-3,4,4a,5,6,10b-hexahydro-2h-naphto[1,2-b][1,4]oxazine derivatives, process for producing them and pharmaceutical compositions containing them | |
| Remy et al. | A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogs having furan nuclei fused to the 10, 11-vinylene bridge | |
| EP0002512B1 (en) | Imino-bridged benzocycloheptapyridines, process for their preparation and pharmaceutical composition thereof | |
| AU8818298A (en) | 1,3-dioxolo/4,5-h//2,3/benzodiazepine derivatives as ampa/kainate receptor inhibitors | |
| Schut et al. | Bicyclic Mannich bases. 1. Psychotropic activity of 2-(4-aryl-l-piperazinyl) bicyclo [3.3. 1] nonan-9-ones and derivatives | |
| DK147280B (da) | Analogifremgangsmaade til fremstilling af 4-amino-benzo(b)bicyklo(3,3,1)nonenderivater | |
| NZ270500A (en) | 1-indenylethyl-4-naphthyl piperazines and pharmaceutical compositions thereof | |
| Peglion et al. | 2-aminoindan compounds as 5HT 1B antagonists | |
| Kapadia | Synthesis of novel aporphine-inspired neuroreceptor ligands |