JPS6144866B2 - - Google Patents
Info
- Publication number
- JPS6144866B2 JPS6144866B2 JP52090547A JP9054777A JPS6144866B2 JP S6144866 B2 JPS6144866 B2 JP S6144866B2 JP 52090547 A JP52090547 A JP 52090547A JP 9054777 A JP9054777 A JP 9054777A JP S6144866 B2 JPS6144866 B2 JP S6144866B2
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- alkyl group
- hydrogen
- tetrahydro
- group
- 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.)
- Expired
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims description 57
- 150000001875 compounds Chemical class 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 34
- -1 monoalkylaminoalkyl Chemical group 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 9
- SRQMOHGEWMZUOI-UHFFFAOYSA-N 1,2,4,5-tetrahydro-2-benzazepin-3-one Chemical compound C1NC(=O)CCC2=CC=CC=C21 SRQMOHGEWMZUOI-UHFFFAOYSA-N 0.000 claims description 4
- SYIUPRKONIOYIL-UHFFFAOYSA-N 1-benzazepin-3-one Chemical compound N1=CC(=O)C=CC2=CC=CC=C21 SYIUPRKONIOYIL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- PRZKFIAKTRLPHM-UHFFFAOYSA-N 2,4-dimethyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1N(C)C(=O)C(C)CC2=CC=CC=C21 PRZKFIAKTRLPHM-UHFFFAOYSA-N 0.000 claims description 2
- JGODRPDYQKKFNX-UHFFFAOYSA-N 2-methyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1CC(=O)N(C)CC2=CC=CC=C21 JGODRPDYQKKFNX-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims 2
- 238000010531 catalytic reduction reaction Methods 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- POCNBPQSYBGIQA-UHFFFAOYSA-N 5-phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one Chemical compound C12=CC=CC=C2CNC(=O)CC1C1=CC=CC=C1 POCNBPQSYBGIQA-UHFFFAOYSA-N 0.000 claims 1
- JOGXEGGNJKSTNE-UHFFFAOYSA-N 8-methyl-1,2,4,5-tetrahydro-2-benzazepin-3-one Chemical compound C1CC(=O)NCC2=CC(C)=CC=C21 JOGXEGGNJKSTNE-UHFFFAOYSA-N 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 210000000748 cardiovascular system Anatomy 0.000 claims 1
- 238000000921 elemental analysis Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000001953 recrystallisation Methods 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000009835 boiling Methods 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- DAUQPTASRUQBLG-UHFFFAOYSA-N 2-benzazepin-3-one Chemical class C1=NC(=O)C=CC2=CC=CC=C21 DAUQPTASRUQBLG-UHFFFAOYSA-N 0.000 description 5
- 229940126062 Compound A Drugs 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229960004526 piracetam Drugs 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 4
- 241001111317 Chondrodendron tomentosum Species 0.000 description 4
- 239000008709 Curare Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000005227 gel permeation chromatography Methods 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- KZIGUGMFQVNQFJ-UHFFFAOYSA-N 2-bromo-1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C(Br)=C1 KZIGUGMFQVNQFJ-UHFFFAOYSA-N 0.000 description 3
- BWRCVZCXQGNQHZ-UHFFFAOYSA-N 3-(2-bromo-4-chlorophenyl)-2-methylpropanoic acid Chemical group OC(=O)C(C)CC1=CC=C(Cl)C=C1Br BWRCVZCXQGNQHZ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- VCBSMHZNRBWEIJ-UHFFFAOYSA-L trimethyl-[5-[5-(trimethylazaniumyl)pentoxy]pentyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCCCCOCCCCC[N+](C)(C)C VCBSMHZNRBWEIJ-UHFFFAOYSA-L 0.000 description 3
- RAVBNEMTZQOKCD-SNAWJCMRSA-N (e)-3-(2-bromo-4-methylphenyl)prop-2-enoic acid Chemical compound CC1=CC=C(\C=C\C(O)=O)C(Br)=C1 RAVBNEMTZQOKCD-SNAWJCMRSA-N 0.000 description 2
- DATPMYQHQOKUEM-UHFFFAOYSA-N 2,8-dimethyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1CC(=O)N(C)CC2=CC(C)=CC=C21 DATPMYQHQOKUEM-UHFFFAOYSA-N 0.000 description 2
- SRNKAXARUZJZLW-UHFFFAOYSA-N 2-(3-oxo-4,5-dihydro-1h-2-benzazepin-2-yl)acetamide Chemical compound C1CC(=O)N(CC(=O)N)CC2=CC=CC=C21 SRNKAXARUZJZLW-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- DYMSJANEHGEKSI-UHFFFAOYSA-N 3,3-diphenylpropanamide Chemical compound C=1C=CC=CC=1C(CC(=O)N)C1=CC=CC=C1 DYMSJANEHGEKSI-UHFFFAOYSA-N 0.000 description 2
- HHHCLLQAXLRKHD-UHFFFAOYSA-N 3-(4-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-2-yl)propanamide Chemical compound C1N(CCC(N)=O)C(=O)C(C)CC2=CC=CC=C21 HHHCLLQAXLRKHD-UHFFFAOYSA-N 0.000 description 2
- LHPMWJHMUMOASG-UHFFFAOYSA-N 8-chloro-2-(2-ethoxyacetyl)-4-methyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1C(C)C(=O)N(C(=O)COCC)CC2=CC(Cl)=CC=C21 LHPMWJHMUMOASG-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- QENKZUWPSOHMBN-AATRIKPKSA-N methyl (e)-3-(2-bromo-4-methylphenyl)prop-2-enoate Chemical group COC(=O)\C=C\C1=CC=C(C)C=C1Br QENKZUWPSOHMBN-AATRIKPKSA-N 0.000 description 2
- BODNANJJTPAXQX-UHFFFAOYSA-N methyl 3-(4-chloro-2-cyanophenyl)-2-methylpropanoate Chemical compound COC(=O)C(C)CC1=CC=C(Cl)C=C1C#N BODNANJJTPAXQX-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- NJBBLOIWMSYVCQ-OKHMJZBSSA-N (4r)-n-tert-butyl-3-[2-hydroxy-3-[[(2r)-2-[(2-isoquinolin-5-yloxyacetyl)amino]-3-methylsulfanylpropanoyl]amino]-4-phenylbutanoyl]-1,3-thiazolidine-4-carboxamide Chemical compound O=C([C@@H](NC(=O)COC=1C2=CC=NC=C2C=CC=1)CSC)NC(C(O)C(=O)N1[C@@H](CSC1)C(=O)NC(C)(C)C)CC1=CC=CC=C1 NJBBLOIWMSYVCQ-OKHMJZBSSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- MOQIYJQMURMBTL-UHFFFAOYSA-N 1-(dibromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(C(Br)Br)=C1 MOQIYJQMURMBTL-UHFFFAOYSA-N 0.000 description 1
- KXXZULOWQUGDMR-UHFFFAOYSA-N 1-bromo-2-(1-bromoethyl)benzene Chemical compound CC(Br)C1=CC=CC=C1Br KXXZULOWQUGDMR-UHFFFAOYSA-N 0.000 description 1
- LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical class BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
- BLZNSXFQRKVFRP-UHFFFAOYSA-N 1-bromo-4-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Br)C(C)=C1 BLZNSXFQRKVFRP-UHFFFAOYSA-N 0.000 description 1
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical group CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- SIQBPWRTJNBBER-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-2-benzazepine Chemical class C1CCNCC2=CC=CC=C21 SIQBPWRTJNBBER-UHFFFAOYSA-N 0.000 description 1
- JQRDOUUDFSXQGT-UHFFFAOYSA-N 2-(hydroxymethyl)-4-methyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1N(CO)C(=O)C(C)CC2=CC=CC=C21 JQRDOUUDFSXQGT-UHFFFAOYSA-N 0.000 description 1
- CSUUXPHPCXHYGY-UHFFFAOYSA-N 2-bromo-4-chloro-1-methylbenzene Chemical compound CC1=CC=C(Cl)C=C1Br CSUUXPHPCXHYGY-UHFFFAOYSA-N 0.000 description 1
- ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 2-ethoxyacetyl chloride Chemical compound CCOCC(Cl)=O ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 0.000 description 1
- DOZZSWAOPDYVLH-UHFFFAOYSA-N 2-phenylpropanamide Chemical class NC(=O)C(C)C1=CC=CC=C1 DOZZSWAOPDYVLH-UHFFFAOYSA-N 0.000 description 1
- RZPFVRFSYMUDJO-UHFFFAOYSA-N 2h-naphthalen-1-one Chemical compound C1=CC=C2C(=O)CC=CC2=C1 RZPFVRFSYMUDJO-UHFFFAOYSA-N 0.000 description 1
- KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical class C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 1
- CMEASCHYTXEXMS-UHFFFAOYSA-N 3-(3',4'-dimethoxyphenyl)propanamide Natural products COC1=CC=C(CCC(N)=O)C=C1OC CMEASCHYTXEXMS-UHFFFAOYSA-N 0.000 description 1
- BOFWNXWDBTUWEM-UHFFFAOYSA-N 3-(3-methoxyphenyl)propanamide Chemical compound COC1=CC=CC(CCC(N)=O)=C1 BOFWNXWDBTUWEM-UHFFFAOYSA-N 0.000 description 1
- OGCPPJKWRVXYJG-UHFFFAOYSA-N 3-(5-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-2-yl)propanenitrile Chemical compound CC1CC(=O)N(CCC#N)CC2=CC=CC=C12 OGCPPJKWRVXYJG-UHFFFAOYSA-N 0.000 description 1
- ODWQUDZAIYZJRS-UHFFFAOYSA-N 4-methyl-2-(2-methylpropyl)-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1C(C)C(=O)N(CC(C)C)CC2=CC=CC=C21 ODWQUDZAIYZJRS-UHFFFAOYSA-N 0.000 description 1
- ALHFSHYCVKXFJN-UHFFFAOYSA-N 7-methoxy-1-phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one Chemical compound N1C(=O)CCC2=CC(OC)=CC=C2C1C1=CC=CC=C1 ALHFSHYCVKXFJN-UHFFFAOYSA-N 0.000 description 1
- XWHKFXPYDKUILI-UHFFFAOYSA-N 7-methoxy-2-methyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1N(C)C(=O)CCC2=CC(OC)=CC=C21 XWHKFXPYDKUILI-UHFFFAOYSA-N 0.000 description 1
- CQYKFZQYJFWFRG-UHFFFAOYSA-N 8-chloro-2-(2-hydroxyethyl)-4-methyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1N(CCO)C(=O)C(C)CC2=CC=C(Cl)C=C21 CQYKFZQYJFWFRG-UHFFFAOYSA-N 0.000 description 1
- XFVZHPWCKXZWRG-UHFFFAOYSA-N 8-methyl-2-pentyl-4,5-dihydro-1h-2-benzazepin-3-one Chemical compound C1CC(=O)N(CCCCC)CC2=CC(C)=CC=C21 XFVZHPWCKXZWRG-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 208000031872 Body Remains Diseases 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
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 229920002261 Corn starch Chemical class 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Chemical class 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- 238000004566 IR spectroscopy 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
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- 238000006923 Schmidt rearrangement reaction Methods 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 239000008120 corn starch Chemical class 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- GEEGDJDFHDNCRR-UHFFFAOYSA-N diethyl 2-[2-(2-bromo-4-chlorophenyl)ethyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CCC1=CC=C(Cl)C=C1Br GEEGDJDFHDNCRR-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Chemical class 0.000 description 1
- 229920000159 gelatin Chemical class 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- GQYLTTCTPAIQCT-AATRIKPKSA-N methyl (e)-3-(2-cyano-4-methylphenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=C(C)C=C1C#N GQYLTTCTPAIQCT-AATRIKPKSA-N 0.000 description 1
- BXQBBYGLLCYPFI-UHFFFAOYSA-N methyl 2-cyano-3-(4-methylphenyl)prop-2-enoate Chemical compound COC(=O)C(C#N)=CC1=CC=C(C)C=C1 BXQBBYGLLCYPFI-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- ODWMQCSJRJKJNQ-UHFFFAOYSA-N n-(hydroxymethyl)-3,3-diphenylpropanamide Chemical compound C=1C=CC=CC=1C(CC(=O)NCO)C1=CC=CC=C1 ODWMQCSJRJKJNQ-UHFFFAOYSA-N 0.000 description 1
- ARFOJLSKAAEQNO-UHFFFAOYSA-N n-[3-(5-methyl-3-oxo-4,5-dihydro-1h-2-benzazepin-2-yl)propyl]acetamide Chemical compound CC1CC(=O)N(CCCNC(C)=O)CC2=CC=CC=C12 ARFOJLSKAAEQNO-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229950009119 oxydipentonium chloride Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 229920001592 potato starch Chemical class 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Chemical class 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/14—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the side-chain of aromatic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
- C07C25/02—Monocyclic aromatic halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
- C07C57/60—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB31846/76A GB1525845A (en) | 1976-07-30 | 1976-07-30 | 1,2,4,5-tetrahydro-3h-2-benzazepin-3-ones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5318591A JPS5318591A (en) | 1978-02-20 |
| JPS6144866B2 true JPS6144866B2 (en, 2012) | 1986-10-04 |
Family
ID=10329274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9054777A Granted JPS5318591A (en) | 1976-07-30 | 1977-07-29 | 1*2*4*55tetrahydroo3hh22 benzazepine 33one derivative |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4080449A (en, 2012) |
| JP (1) | JPS5318591A (en, 2012) |
| BE (1) | BE857191A (en, 2012) |
| DE (1) | DE2733868C2 (en, 2012) |
| FR (1) | FR2359826A1 (en, 2012) |
| GB (1) | GB1525845A (en, 2012) |
| NL (1) | NL7708275A (en, 2012) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS575689A (en) * | 1980-06-13 | 1982-01-12 | Toray Ind Inc | Unit for microcarrier cultivation |
| JPS57132877A (en) * | 1981-02-12 | 1982-08-17 | Hitachi Ltd | High-viscosity cultivation device |
| JP2699511B2 (ja) * | 1988-01-29 | 1998-01-19 | 武田薬品工業株式会社 | 置換アミン類 |
| JP2871811B2 (ja) * | 1990-02-28 | 1999-03-17 | サントリー株式会社 | 縮合７員環系化合物 |
| US5395855A (en) * | 1990-05-07 | 1995-03-07 | Ciba-Geigy Corporation | Hydrazones |
| US5430145A (en) * | 1990-10-18 | 1995-07-04 | Merrell Dow Pharmaceuticals Inc. | Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace |
| US5308841A (en) * | 1990-12-21 | 1994-05-03 | Merrell Dow Pharmaceuticals Inc. | Amino and nitro containing tricyclic compounds useful as inhibitors of ACE |
| CA2078759C (en) * | 1991-09-27 | 2003-09-16 | Alan M. Warshawsky | Novel carboxyalkyl derivatives useful as inhibitors of enkephalinase and ace |
| US5455242A (en) * | 1991-09-27 | 1995-10-03 | Merrell Dow Pharmaceuticals Inc. | Carboxyalkyl tricyclic derivatives useful as inhibitors of enkephalinase and ace |
| US5457196A (en) * | 1991-09-27 | 1995-10-10 | Merrell Dow Pharmaceuticals Inc. | 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE |
| DK0534363T3 (da) * | 1991-09-27 | 1997-09-22 | Merrell Pharma Inc | 2-substituerede indan-2-mercaptoacetylamid-forbindelse med inhiberende virkning på enkephalinase og ACE. |
| HU220596B1 (hu) * | 1992-02-14 | 2002-03-28 | Merrell Dow Pharmaceuticals Inc. | 7-Szubsztituált pirido-benzazepin-karbonsav-származékok, ezeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| EP0640086B1 (en) * | 1992-05-15 | 1999-08-04 | Merrell Pharmaceuticals Inc. | MERCAPTOACETYLAMIDO PYRIDAZO[ 1,2-a][1,2]DIAZEPINE DERIVATIVES USEFUL AS INHIBITORS OF ENKEPHALINASE AND ACE |
| US5420271A (en) * | 1992-08-24 | 1995-05-30 | Merrell Dow Pharmaceuticals, Inc. | 2-substituted indane-2-mercaptoacetylamide tricyclic derivatives useful as inhibitors of enkephalinase |
| WO1994010193A1 (en) * | 1992-10-30 | 1994-05-11 | Merrell Dow Pharmaceuticals Inc. | Novel mercaptoacetylamide bicyclic lactam derivatives useful as inhibitors of enkephalinase and ace |
| FI963166L (fi) * | 1994-02-14 | 1996-08-13 | Merrell Pharma Inc | Uusia merkaptoasetyyliamididisulfidijohdannaisia, jotka ovat käyttökelpoisia enkefalinaasin ja ACE:n inhibiittoreina |
| ES2145267T3 (es) * | 1994-02-14 | 2000-07-01 | Merrell Pharma Inc | Nuevos derivados bisulfuro de mercaptoacetilamido de 1,3,4,5-tetrahidro-benzo(c)azepin-3-ona utiles como inhibidores de la encefalinasa y del enzima de conversion de la angiotensina. |
| US5530013A (en) * | 1994-02-14 | 1996-06-25 | American Home Products Corporation | Venlafaxine in the inducement of cognition enhancement |
| PT745081E (pt) * | 1994-02-14 | 2002-04-29 | Merrell Pharma Inc | Derivados de dissulfureto de inda-2-mercaptoacetilamida uteis como inibidores da encefalinase |
| AU689192B2 (en) * | 1994-02-14 | 1998-03-26 | Merrell Pharmaceuticals Inc. | Novel 2-substituted indane-2-mercaptoacetylamide disulfide derivatives useful as inhibitors of enkephalinase and ace |
| US5484783A (en) * | 1994-03-24 | 1996-01-16 | Merrell Dow Pharmaceuticals Inc. | Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic mercaptoacetylamide and benzazapine derivatives |
| AU698320B2 (en) * | 1994-03-24 | 1998-10-29 | Merrell Pharmaceuticals Inc. | Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic aminoacetylmercapto derivatives |
| DK0751774T3 (da) * | 1994-03-24 | 2003-12-08 | Merrell Pharma Inc | Hypocholesterolæmiske mercaptoacetylamiddisulfid-derivater |
| US6683075B1 (en) | 1996-12-23 | 2004-01-27 | Athena Neurosciences, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use |
| US6635632B1 (en) * | 1996-12-23 | 2003-10-21 | Athena Neurosciences, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| US6774125B2 (en) * | 1998-06-22 | 2004-08-10 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| US6509331B1 (en) | 1998-06-22 | 2003-01-21 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| US6552013B1 (en) | 1998-06-22 | 2003-04-22 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| US6569851B1 (en) * | 1998-06-22 | 2003-05-27 | Elan Pharmaceutials, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| US6958330B1 (en) | 1998-06-22 | 2005-10-25 | Elan Pharmaceuticals, Inc. | Polycyclic α-amino-ε-caprolactams and related compounds |
| US6528505B1 (en) | 1998-06-22 | 2003-03-04 | Elan Pharmaceuticals, Inc. | Cyclic amino acid compounds pharmaceutical compositions comprising same and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| EP1230220A1 (en) * | 1999-11-09 | 2002-08-14 | Eli Lilly And Company | Beta-aminoacid compounds useful for inhibiting beta-amyloid peptide release and/or its synthesis |
| GB0119305D0 (en) | 2001-04-12 | 2001-10-03 | Aventis Pharma Gmbh | Mercaptoacetylamide derivatives,a process for their preparation and their use |
| KR100408919B1 (ko) * | 2001-06-25 | 2003-12-11 | 바이오네스트 주식회사 | 에피나스틴 염산염의 중간체인 2,6-모르판트리돈의 새로운제조방법 |
| US20050192265A1 (en) * | 2003-03-20 | 2005-09-01 | Thompson Richard C. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds |
| KR20080044840A (ko) | 2005-07-15 | 2008-05-21 | 에이엠알 테크놀로지, 인크. | 아릴- 및 헤테로아릴-치환된 테트라히드로벤자제핀, 및노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기위한 용도 |
| JP5098011B2 (ja) * | 2006-11-20 | 2012-12-12 | 国立大学法人山口大学 | 創傷治癒促進剤 |
| CN102796044A (zh) * | 2012-08-24 | 2012-11-28 | 南通大学 | 2,3,4,5-四氢-1h-2-苯并氮杂卓-1-酮衍生物的化学合成方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1472930A (fr) | 1965-04-02 | 1967-03-17 | Alphachimie | Nouveaux dérivés de la 2, 3, 4, 5-tétrahydro-(1eta)-2-benzazépine et leurs procédés de fabrication |
-
1976
- 1976-07-30 GB GB31846/76A patent/GB1525845A/en not_active Expired
-
1977
- 1977-07-26 NL NL7708275A patent/NL7708275A/xx not_active Application Discontinuation
- 1977-07-27 BE BE1008302A patent/BE857191A/xx not_active IP Right Cessation
- 1977-07-27 US US05/819,279 patent/US4080449A/en not_active Expired - Lifetime
- 1977-07-27 DE DE2733868A patent/DE2733868C2/de not_active Expired
- 1977-07-27 FR FR7723370A patent/FR2359826A1/fr active Granted
- 1977-07-29 JP JP9054777A patent/JPS5318591A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| BE857191A (fr) | 1978-01-27 |
| FR2359826A1 (fr) | 1978-02-24 |
| NL7708275A (nl) | 1978-02-01 |
| GB1525845A (en) | 1978-09-20 |
| DE2733868A1 (de) | 1978-02-02 |
| US4080449A (en) | 1978-03-21 |
| DE2733868C2 (de) | 1987-05-14 |
| FR2359826B1 (en, 2012) | 1980-04-04 |
| JPS5318591A (en) | 1978-02-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS6144866B2 (en, 2012) | ||
| DE69303569T2 (de) | Arylalkyl(thio)amide mit Melatonin-Rezeptor-Selektivität und Prozess zu ihrer Darstellung | |
| JPS6134426B2 (en, 2012) | ||
| WO1998058901A1 (fr) | Derives de la 3-anilino-2-cycloalcenone | |
| CH653684A5 (fr) | Derives de carbostyrile, procede pour leur preparation et compositions les contenant. | |
| JP2682705B2 (ja) | ２，６−ジクロロフェニルアミノベンゼン酢酸誘導体及びジフェニルアミン誘導体の製造方法。 | |
| CH648827A5 (fr) | Phenoxyamines heterocycliques substituees, leur preparation et medicaments consistant de ou comprenant ces composes. | |
| CA1042905A (fr) | Procede de preparation de nouveaux azabicycloalcanes disubstitues | |
| JPS6011901B2 (ja) | 新規の脂肪族置換された４−フエニル−ピペリジン | |
| DE3300522C2 (en, 2012) | ||
| US4616011A (en) | Novel indole derivatives and pharmaceutical compositions containing same | |
| JPH0455427B2 (en, 2012) | ||
| JPH0533696B2 (en, 2012) | ||
| EP0005091B1 (fr) | Nouvelles pipérazines monosubstituées, leurs procédés de préparation et les compositions pharmaceutiques les renfermant | |
| FI61694B (fi) | Foerfarande foer framstaellning av substituerade arylalkylaminer med blodtrycket och hjaertslagfrekvensen saenkande verkan | |
| CH643258A5 (fr) | Octahydro-2h-pyrrolo(3,4-g)quinoleines. | |
| US9611217B2 (en) | Synthetic processes of carprofen | |
| US4038413A (en) | Treating iron deficiency anaemia | |
| JP2552436B2 (ja) | ベンゾ〔ａ〕キノリジノン誘導体の製造方法 | |
| US4548947A (en) | 1-(Substituted-aryl)-dihydro-1H-pyrrolizine-3,5-[2H,6H-]diones and use for reversing amnesia | |
| JP2002308851A (ja) | ６−アミノメチル−６，１１−ジヒドロ−５Ｈ−ジベンゾ［ｂ，ｅ］アゼピンの製造方法 | |
| JPH0825880B2 (ja) | ナフトキサジン類の新用途 | |
| US4080450A (en) | 2-Carbamoyl-1,2,4,5-tetrahydro-3H-2-benzazepin-3-ones | |
| KR19990044479A (ko) | 4-(시클로알킬)피페리딘 유도체와 4-(시클로알킬알킬)피페리딘유도체,그것들의 제법 및 치료학적 사용 | |
| IL27300A (en) | H5 Compounds - Benzo [4, 5] Cyclo - Feta [B - 2, 1] Pyridine and Compounds 10, 11 - Dihydro Hydrates, Processes for Their Production and Pharmaceutical Preparations Containing Them |