DE10148425A1 - Chromane - Google Patents
ChromaneInfo
- Publication number
- DE10148425A1 DE10148425A1 DE10148425A DE10148425A DE10148425A1 DE 10148425 A1 DE10148425 A1 DE 10148425A1 DE 10148425 A DE10148425 A DE 10148425A DE 10148425 A DE10148425 A DE 10148425A DE 10148425 A1 DE10148425 A1 DE 10148425A1
- Authority
- DE
- Germany
- Prior art keywords
- mmol
- dihydro
- compounds
- chromen
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims 2
- 208000029028 brain injury Diseases 0.000 claims 1
- 210000003625 skull Anatomy 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 5
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- 150000001843 chromanes Chemical class 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000012071 phase Substances 0.000 description 12
- -1 salts Compounds Chemical class 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- GRPGDBKIWXIPHM-UHFFFAOYSA-N ethyl 6-methoxy-7-phenylmethoxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=C2OC(C(=O)OCC)CCC2=CC(OC)=C1OCC1=CC=CC=C1 GRPGDBKIWXIPHM-UHFFFAOYSA-N 0.000 description 4
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- PMUKDITVUUEKCL-AREMUKBSSA-N [(2r)-2-[[phenylmethoxycarbonyl-[4-(1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]amino]methyl]-3,4-dihydro-2h-chromen-6-yl] acetate Chemical compound C([C@@H]1OC2=CC=C(C=C2CC1)OC(=O)C)N(CCCCN1S(C2=CC=CC=C2C1=O)(=O)=O)C(=O)OCC1=CC=CC=C1 PMUKDITVUUEKCL-AREMUKBSSA-N 0.000 description 3
- BITUJTOHCYCQDX-OAHLLOKOSA-N [(2r)-6-methoxy-7-phenylmethoxy-3,4-dihydro-2h-chromen-2-yl]methanol Chemical compound O([C@@H](CO)CCC=1C=C2OC)C=1C=C2OCC1=CC=CC=C1 BITUJTOHCYCQDX-OAHLLOKOSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- DUPIUWHQWBDPCP-XMMPIXPASA-N benzyl n-[[(2r)-3,4-dihydro-2h-chromen-2-yl]methyl]-n-[4-(1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]carbamate Chemical compound O=C1C2=CC=CC=C2S(=O)(=O)N1CCCCN(C[C@@H]1OC2=CC=CC=C2CC1)C(=O)OCC1=CC=CC=C1 DUPIUWHQWBDPCP-XMMPIXPASA-N 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 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
- RXQGJGVDTAXBQZ-UHFFFAOYSA-N ethyl 6-methoxy-4-oxo-7-phenylmethoxychromene-2-carboxylate Chemical compound C1=C2OC(C(=O)OCC)=CC(=O)C2=CC(OC)=C1OCC1=CC=CC=C1 RXQGJGVDTAXBQZ-UHFFFAOYSA-N 0.000 description 3
- ROKVTBVTGYCEDT-UHFFFAOYSA-N ethyl 7-hydroxy-6-methoxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound COC1=C(O)C=C2OC(C(=O)OCC)CCC2=C1 ROKVTBVTGYCEDT-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- YXJGZUVJMHBKFH-UHFFFAOYSA-N methyl 4-hydroxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OC)CC(O)C2=C1 YXJGZUVJMHBKFH-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 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
- 238000000825 ultraviolet detection Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- IGKYREHZJIHPML-UNTBIKODSA-N 2-[4-[[(2r)-3,4-dihydro-2h-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one;hydron;chloride Chemical compound Cl.O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCNC[C@@H]1OC2=CC=CC=C2CC1 IGKYREHZJIHPML-UNTBIKODSA-N 0.000 description 2
- BXHPCMIYSZRTAL-UNTBIKODSA-N 2-[4-[[(2r)-6-hydroxy-3,4-dihydro-2h-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one;hydrochloride Chemical compound Cl.O=C1C2=CC=CC=C2S(=O)(=O)N1CCCCNC[C@@H]1OC2=CC=C(O)C=C2CC1 BXHPCMIYSZRTAL-UNTBIKODSA-N 0.000 description 2
- IMSYZRUTJQMZEG-PKLMIRHRSA-N 2-[4-[[(2r)-7-hydroxy-6-methoxy-3,4-dihydro-2h-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one;hydrochloride Chemical compound Cl.O=C1C2=CC=CC=C2S(=O)(=O)N1CCCCNC[C@H]1CCC(C=C(C(=C2)O)OC)=C2O1 IMSYZRUTJQMZEG-PKLMIRHRSA-N 0.000 description 2
- LOGNLNMVPONWSI-UHFFFAOYSA-N 2-[4-[benzyl-[[4-[tert-butyl(dimethyl)silyl]oxy-3,4-dihydro-2h-chromen-2-yl]methyl]amino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound O1C2=CC=CC=C2C(O[Si](C)(C)C(C)(C)C)CC1CN(CCCCN1S(C2=CC=CC=C2C1=O)(=O)=O)CC1=CC=CC=C1 LOGNLNMVPONWSI-UHFFFAOYSA-N 0.000 description 2
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
- SLSUBOSBTBJRCO-UHFFFAOYSA-N 4-hydroxy-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2C(O)CC(C(O)=O)OC2=C1 SLSUBOSBTBJRCO-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-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
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 2
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- IRZXLQJVOAQNAO-UHFFFAOYSA-N n-benzyl-1-[4-[tert-butyl(dimethyl)silyl]oxy-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound O1C2=CC=CC=C2C(O[Si](C)(C)C(C)(C)C)CC1CNCC1=CC=CC=C1 IRZXLQJVOAQNAO-UHFFFAOYSA-N 0.000 description 2
- BHAGEKGIBBDSFZ-UHFFFAOYSA-N n-benzyl-4-[tert-butyl(dimethyl)silyl]oxy-3,4-dihydro-2h-chromene-2-carboxamide Chemical compound O1C2=CC=CC=C2C(O[Si](C)(C)C(C)(C)C)CC1C(=O)NCC1=CC=CC=C1 BHAGEKGIBBDSFZ-UHFFFAOYSA-N 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 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
- 238000010626 work up procedure Methods 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- YIVUYWDMNPVHOV-UHFFFAOYSA-N 1,1-dioxo-1,2-benzothiazol-3-one;hydrochloride Chemical compound Cl.C1=CC=C2C(=O)NS(=O)(=O)C2=C1 YIVUYWDMNPVHOV-UHFFFAOYSA-N 0.000 description 1
- BEJGLFVJZIJLDQ-UHFFFAOYSA-N 1,1-dioxo-2-prop-2-ynyl-1,2-benzothiazol-3-one Chemical compound C1=CC=C2C(=O)N(CC#C)S(=O)(=O)C2=C1 BEJGLFVJZIJLDQ-UHFFFAOYSA-N 0.000 description 1
- FIPKPTOKXILFGI-UHFFFAOYSA-N 1-(2-hydroxy-5-methoxy-4-phenylmethoxyphenyl)ethanone Chemical compound COC1=CC(C(C)=O)=C(O)C=C1OCC1=CC=CC=C1 FIPKPTOKXILFGI-UHFFFAOYSA-N 0.000 description 1
- LDLMQHQKQUUSMO-UHFFFAOYSA-N 2-(4-bromobutyl)-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=CC=C2S(=O)(=O)N(CCCCBr)C(=O)C2=C1 LDLMQHQKQUUSMO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- MJDAVVKBAQCMFJ-UHFFFAOYSA-N 2-[4-[(4-hydroxy-3,4-dihydro-2h-chromen-2-yl)methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound O1C2=CC=CC=C2C(O)CC1CNCCCCN1S(=O)(=O)C2=CC=CC=C2C1=O MJDAVVKBAQCMFJ-UHFFFAOYSA-N 0.000 description 1
- FYVNJZAQBFFIFK-SSEXGKCCSA-N 2-[4-[benzyl-[[(2r)-6-methoxy-7-phenylmethoxy-3,4-dihydro-2h-chromen-2-yl]methyl]amino]but-2-ynyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C([C@H]1CCC=2C=C(C(=CC=2O1)OCC=1C=CC=CC=1)OC)N(CC#CCN1S(C2=CC=CC=C2C1=O)(=O)=O)CC1=CC=CC=C1 FYVNJZAQBFFIFK-SSEXGKCCSA-N 0.000 description 1
- ARTIHKKKUPIMLH-UHFFFAOYSA-N 2h-1,2-benzothiazol-6-one Chemical compound O=C1C=CC2=CNSC2=C1 ARTIHKKKUPIMLH-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
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- YOELOXQSYPDESY-MRXNPFEDSA-N C(C1=CC=CC=C1)OC1=C(C=C2CC[C@H](OC2=C1)CC)OC Chemical compound C(C1=CC=CC=C1)OC1=C(C=C2CC[C@H](OC2=C1)CC)OC YOELOXQSYPDESY-MRXNPFEDSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 206010008089 Cerebral artery occlusion Diseases 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
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 206010053487 Exposure to toxic agent Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000029033 Spinal Cord disease Diseases 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
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- ZAYMRPIJNLRXJH-UHFFFAOYSA-N dichloromethane methanesulfonyl chloride Chemical compound CS(=O)(=O)Cl.ClCCl ZAYMRPIJNLRXJH-UHFFFAOYSA-N 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009297 electrocoagulation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229940082150 encore Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- GRPGDBKIWXIPHM-MRXNPFEDSA-N ethyl (2r)-6-methoxy-7-phenylmethoxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C([C@@H](OC1=C2)C(=O)OCC)CC1=CC(OC)=C2OCC1=CC=CC=C1 GRPGDBKIWXIPHM-MRXNPFEDSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000003446 ligand Substances 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
- 230000007257 malfunction Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GJJUEEGRVKSEEU-UHFFFAOYSA-N methyl 4-[tert-butyl(dimethyl)silyl]oxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OC)CC(O[Si](C)(C)C(C)(C)C)C2=C1 GJJUEEGRVKSEEU-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- GWWZKXQHXCOMEH-UHFFFAOYSA-N n-benzyl-4-hydroxy-3,4-dihydro-2h-chromene-2-carboxamide Chemical compound O1C2=CC=CC=C2C(O)CC1C(=O)NCC1=CC=CC=C1 GWWZKXQHXCOMEH-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- YGYBFMRFXNDIPO-QGZVFWFLSA-N repinotan Chemical class O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCNC[C@@H]1OC2=CC=CC=C2CC1 YGYBFMRFXNDIPO-QGZVFWFLSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10148425A DE10148425A1 (de) | 2001-10-01 | 2001-10-01 | Chromane |
| CA002462142A CA2462142A1 (en) | 2001-10-01 | 2002-09-18 | Benzisothiazolyl-substituted aminomethyl chromanes for treating diseases of the central nervous system |
| PCT/EP2002/010447 WO2003029250A1 (de) | 2001-10-01 | 2002-09-18 | Benzisothiazolyl-substituerte aminomethylcromane zur behandlung von erkrankungen des zentralen nervensystems |
| US10/490,315 US6919360B2 (en) | 2001-10-01 | 2002-09-18 | Benzisothiazolyl-substituted aminomethyl chromanes for treating diseases of the central nervous system |
| JP2003532498A JP2005507901A (ja) | 2001-10-01 | 2002-09-18 | クロマン類 |
| EP02767489A EP1434777A1 (de) | 2001-10-01 | 2002-09-18 | Benzisothiazolyl-substituierte aminomethylchromane zur behandlung von erkrankungen des zentralen nervensystems |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10148425A DE10148425A1 (de) | 2001-10-01 | 2001-10-01 | Chromane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10148425A1 true DE10148425A1 (de) | 2003-04-17 |
Family
ID=7700998
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10148425A Withdrawn DE10148425A1 (de) | 2001-10-01 | 2001-10-01 | Chromane |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6919360B2 (https=) |
| EP (1) | EP1434777A1 (https=) |
| JP (1) | JP2005507901A (https=) |
| CA (1) | CA2462142A1 (https=) |
| DE (1) | DE10148425A1 (https=) |
| WO (1) | WO2003029250A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2199086B1 (es) | 2002-07-31 | 2005-06-01 | Cepa Schwarz Pharma Sl | Nuevos derivados de cicloalcanodionas, procedimiento para su preparacion y sus aplicaciones farmacologicas. |
| ES2238015B1 (es) * | 2004-01-30 | 2006-11-01 | Cepa Schwarz Pharma, S.L. | Derivados de cicloalcanodionas con actividad neuroprotectora. |
| EP1856126A2 (en) * | 2005-02-17 | 2007-11-21 | Wyeth a Corporation of the State of Delaware | Cycloalkylfused indole, benzothiophene, benzofuran and indene derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3901814A1 (de) | 1988-07-28 | 1990-02-01 | Bayer Ag | Substituierte aminomethylzetraline sowie ihre heterocyclischen analoga |
| DE19522088A1 (de) * | 1995-06-19 | 1997-01-02 | Bayer Ag | Benzisothiazolyl-substituierte Aminomethylchromane |
| DE19543476A1 (de) * | 1995-11-22 | 1997-05-28 | Troponwerke Gmbh & Co Kg | Verwendung von substituierten Aminomethyl-chromanen zur Behandlung von Schädel-Hirn-Trauma |
-
2001
- 2001-10-01 DE DE10148425A patent/DE10148425A1/de not_active Withdrawn
-
2002
- 2002-09-18 EP EP02767489A patent/EP1434777A1/de not_active Withdrawn
- 2002-09-18 JP JP2003532498A patent/JP2005507901A/ja not_active Withdrawn
- 2002-09-18 WO PCT/EP2002/010447 patent/WO2003029250A1/de not_active Ceased
- 2002-09-18 US US10/490,315 patent/US6919360B2/en not_active Expired - Fee Related
- 2002-09-18 CA CA002462142A patent/CA2462142A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US6919360B2 (en) | 2005-07-19 |
| JP2005507901A (ja) | 2005-03-24 |
| US20040259924A1 (en) | 2004-12-23 |
| WO2003029250A1 (de) | 2003-04-10 |
| CA2462142A1 (en) | 2003-04-10 |
| EP1434777A1 (de) | 2004-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3784478T2 (de) | Benzopyran-verbindungen, verfahren zu ihrer herstellung und ihre pharmazeutische verwendung. | |
| DE69427704T2 (de) | Neue (r)-5-carbamoyl-8-fluor-3-n,n-disubstituierte-amino-3,4-dihydro-2h-1-benzopyrane | |
| DE69317436T2 (de) | 1,4-benzothiazepine verwendbar als neurologische mittel | |
| DE3486354T2 (de) | Chroman- und Chromenderivate. | |
| DE69716062T2 (de) | Benzofuran-derivate und deren verwendung | |
| JPH05279357A (ja) | アザヘテロサイクリルメチル−クロマン類 | |
| DE69529418T2 (de) | Cyclopropachromencarbonsäure derivate | |
| DE69015322T2 (de) | Substituierte Zyklobutendion-Verbindungen. | |
| JP4190030B2 (ja) | 抗酸化剤としてのアリールアルキルピペラジン化合物 | |
| DE4027278A1 (de) | Heterocyclisch substituierte indolsulfonamide | |
| DE3926001A1 (de) | Chromanderivate | |
| EP0749970B1 (de) | Benzisothiazolyl-substituierte Aminomethylchromane | |
| EP0546389B1 (de) | Piperidylmethyl substituierte Chromanderivate als Wirkstoffe zur Behandlung von Erkrankungen des Zentralnervensystems | |
| DE60311233T2 (de) | Chinolinderivate | |
| DE69518322T2 (de) | C-4 amid substituierte verbindungen und deren verwendung als therapeutische mittel | |
| DE10148425A1 (de) | Chromane | |
| DE4135473A1 (de) | Triazaspirodecanon-methylchromane | |
| DE10153345A1 (de) | Substituierte 1H-Chinoxalin-2-on-Verbindungen und substituierte 4-Aryl- und 4-Heteroarylcyclohexan-Verbindungen | |
| DE69629931T2 (de) | 1-(hetero)aryl-4-(kondensiertes thiazol-2-ylalkyl)-piperazin derivate, deren herstellung und deren verwendung in der behandlung von 5-ht1a-rezeptor vermittelten krankheiten | |
| DE60209937T2 (de) | Chemokinrezeptor-Antagonisten und Methoden zu ihrer Verwendung | |
| JP4861828B2 (ja) | 酸性キノリン誘導体ならびに高血糖に関連する病状の予防および／または治療のためのその使用 | |
| DE60027546T2 (de) | Heterodiazinon-derivate | |
| DE69709869T2 (de) | BENZO[g]CHINOLIN DERIVATE | |
| DE69229501T2 (de) | Benzopyranderivat und dieses als aktives bestandteil enthaltendes antiallergikum | |
| DE19904406A1 (de) | Substituierte Pyrazolcarbonsäuren |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8127 | New person/name/address of the applicant |
Owner name: BAYER HEALTHCARE AG, 51373 LEVERKUSEN, DE |
|
| 8139 | Disposal/non-payment of the annual fee |