JP2821233B2 - 脳乏血の予防ならびに治療におけるアダマンタン誘導体 - Google Patents
脳乏血の予防ならびに治療におけるアダマンタン誘導体Info
- Publication number
- JP2821233B2 JP2821233B2 JP2099117A JP9911790A JP2821233B2 JP 2821233 B2 JP2821233 B2 JP 2821233B2 JP 2099117 A JP2099117 A JP 2099117A JP 9911790 A JP9911790 A JP 9911790A JP 2821233 B2 JP2821233 B2 JP 2821233B2
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- pharmaceutical composition
- amino
- composition according
- carbon atoms
- 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 - Lifetime
Links
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 206010008120 Cerebral ischaemia Diseases 0.000 title claims abstract description 16
- 238000011282 treatment Methods 0.000 title claims abstract description 10
- 230000002265 prevention Effects 0.000 title claims abstract description 7
- 201000006474 Brain Ischemia Diseases 0.000 title claims description 15
- 206010008118 cerebral infarction Diseases 0.000 title claims description 15
- 229940052761 dopaminergic adamantane derivative Drugs 0.000 title abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 239000001257 hydrogen Substances 0.000 claims abstract description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 210000002569 neuron Anatomy 0.000 claims description 5
- 208000028867 ischemia Diseases 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 230000007850 degeneration Effects 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- ZZSRHVAPYKSVGX-UHFFFAOYSA-N 1-bromo-3-ethyl-5,7-dimethyladamantane Chemical compound C1C(C2)(C)CC3(C)CC2(Br)CC1(CC)C3 ZZSRHVAPYKSVGX-UHFFFAOYSA-N 0.000 description 10
- NIKSPBIUZXJSKI-UHFFFAOYSA-N 3-ethyl-5-phenyladamantan-1-ol Chemical compound C1C(CC)(C2)CC(C3)CC1(O)CC32C1=CC=CC=C1 NIKSPBIUZXJSKI-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000001773 anti-convulsant effect Effects 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- -1 for example Chemical group 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- JXYVPFJAUMEJFE-UHFFFAOYSA-N 3-ethyl-5,7-dimethyladamantan-1-amine;hydrochloride Chemical compound Cl.C1C(C2)(C)CC3(C)CC2(N)CC1(CC)C3 JXYVPFJAUMEJFE-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 239000005457 ice water Substances 0.000 description 6
- LPIWUJAIURURAQ-UHFFFAOYSA-N 1-(2-bromoethyl)-3,5-dimethyladamantane Chemical compound C1C(C2)CC3(C)CC1(C)CC2(CCBr)C3 LPIWUJAIURURAQ-UHFFFAOYSA-N 0.000 description 5
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 5
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- ISDSLPMQFWIUPU-UHFFFAOYSA-N 1-propan-2-yladamantane Chemical compound C1C(C2)CC3CC2CC1(C(C)C)C3 ISDSLPMQFWIUPU-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000010265 sodium sulphite Nutrition 0.000 description 4
- XACJBFHSZJWBBP-UHFFFAOYSA-N 1-phenyladamantane Chemical compound C1C(C2)CC(C3)CC1CC23C1=CC=CC=C1 XACJBFHSZJWBBP-UHFFFAOYSA-N 0.000 description 3
- OVQNSGBYKOJYBK-UHFFFAOYSA-N 3-ethyladamantan-1-amine Chemical compound C1C(C2)CC3CC2(N)CC1(CC)C3 OVQNSGBYKOJYBK-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108091006146 Channels Proteins 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 3
- 108090000862 Ion Channels Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 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
- 230000006378 damage Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- FQPYRWAIWQNTFQ-UHFFFAOYSA-N n,3,5-trimethyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(C)CC1(NC)C3 FQPYRWAIWQNTFQ-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- QUCXLVDIVQWYJR-UHFFFAOYSA-N 1-bromo-3,5-dimethyladamantane Chemical compound C1C(C2)CC3(C)CC1(C)CC2(Br)C3 QUCXLVDIVQWYJR-UHFFFAOYSA-N 0.000 description 2
- QUUCNKWMKRZRGC-UHFFFAOYSA-N 1-bromo-3-ethyladamantane Chemical compound C1C(C2)CC3CC2(Br)CC1(CC)C3 QUUCNKWMKRZRGC-UHFFFAOYSA-N 0.000 description 2
- IOPVEZQBHDNEEW-UHFFFAOYSA-N 1-bromo-3-propan-2-yladamantane Chemical compound C1C(C2)CC3CC2(Br)CC1(C(C)C)C3 IOPVEZQBHDNEEW-UHFFFAOYSA-N 0.000 description 2
- CQGHTYOKYHAPCM-UHFFFAOYSA-N 1-cyclohexyladamantane Chemical compound C1CCCCC1C1(C2)CC(C3)CC2CC3C1 CQGHTYOKYHAPCM-UHFFFAOYSA-N 0.000 description 2
- FTNPDAKMYKMVKB-UHFFFAOYSA-N 1-ethyl-3,5-dimethyladamantane Chemical compound C1C(C2)CC3(C)CC2(C)CC1(CC)C3 FTNPDAKMYKMVKB-UHFFFAOYSA-N 0.000 description 2
- SUVNEFNZAWETBP-UHFFFAOYSA-N 3,5-diethyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC1(CC)CC2(CC)C3 SUVNEFNZAWETBP-UHFFFAOYSA-N 0.000 description 2
- WLPZAHQYMVQLHL-UHFFFAOYSA-N 3-cyclohexyladamantan-1-amine Chemical compound C1C(N)(C2)CC(C3)CC1CC32C1CCCCC1 WLPZAHQYMVQLHL-UHFFFAOYSA-N 0.000 description 2
- QJZCXHNEPQJAPJ-UHFFFAOYSA-N 3-ethyl-5,7-dimethyladamantan-1-amine Chemical compound C1C(C2)(C)CC3(C)CC2(N)CC1(CC)C3 QJZCXHNEPQJAPJ-UHFFFAOYSA-N 0.000 description 2
- KMRHMPLKDOCESH-UHFFFAOYSA-N 3-ethyl-5-phenyladamantan-1-amine Chemical compound C1C(CC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 KMRHMPLKDOCESH-UHFFFAOYSA-N 0.000 description 2
- MWXAHLMUYMJXTG-UHFFFAOYSA-N 3-phenyladamantan-1-amine Chemical compound C1C(N)(C2)CC(C3)CC1CC32C1=CC=CC=C1 MWXAHLMUYMJXTG-UHFFFAOYSA-N 0.000 description 2
- DHWQMEWSEZKXHY-UHFFFAOYSA-N 3-propan-2-yladamantan-1-amine;hydrochloride Chemical compound Cl.C1C(C2)CC3CC2(N)CC1(C(C)C)C3 DHWQMEWSEZKXHY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XVIYCJDWYLJQBG-UHFFFAOYSA-N acetic acid;adamantane Chemical compound CC(O)=O.C1C(C2)CC3CC1CC2C3 XVIYCJDWYLJQBG-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000012154 double-distilled water Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 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
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent 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
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- CWNOIUTVJRWADX-UHFFFAOYSA-N 1,3-dimethyladamantane Chemical compound C1C(C2)CC3CC1(C)CC2(C)C3 CWNOIUTVJRWADX-UHFFFAOYSA-N 0.000 description 1
- XSOHXMFFSKTSIT-UHFFFAOYSA-N 1-adamantylmethanamine Chemical compound C1C(C2)CC3CC2CC1(CN)C3 XSOHXMFFSKTSIT-UHFFFAOYSA-N 0.000 description 1
- LZLRNLVOPUAITP-UHFFFAOYSA-N 1-bromo-3-ethyl-5-phenyladamantane Chemical compound C1C(CC)(C2)CC(C3)CC1(Br)CC32C1=CC=CC=C1 LZLRNLVOPUAITP-UHFFFAOYSA-N 0.000 description 1
- VQHPRVYDKRESCL-UHFFFAOYSA-N 1-bromoadamantane Chemical compound C1C(C2)CC3CC2CC1(Br)C3 VQHPRVYDKRESCL-UHFFFAOYSA-N 0.000 description 1
- AZCUIXHZJHFUFI-UHFFFAOYSA-N 1-butyladamantane Chemical compound C1C(C2)CC3CC2CC1(CCCC)C3 AZCUIXHZJHFUFI-UHFFFAOYSA-N 0.000 description 1
- RTVIOLNBTCXFJS-UHFFFAOYSA-N 1-ethyl-3-phenyladamantane Chemical compound C1C(CC)(C2)CC(C3)CC1CC32C1=CC=CC=C1 RTVIOLNBTCXFJS-UHFFFAOYSA-N 0.000 description 1
- LXTHCCWEYOKFSR-UHFFFAOYSA-N 1-ethyladamantane Chemical compound C1C(C2)CC3CC2CC1(CC)C3 LXTHCCWEYOKFSR-UHFFFAOYSA-N 0.000 description 1
- UZUCFTVAWGRMTQ-UHFFFAOYSA-N 1-methyladamantane Chemical compound C1C(C2)CC3CC2CC1(C)C3 UZUCFTVAWGRMTQ-UHFFFAOYSA-N 0.000 description 1
- ICJYJPOGTLSWBN-UHFFFAOYSA-N 3,5-di(propan-2-yl)adamantan-1-amine Chemical compound C1C(C2)CC3(N)CC1(C(C)C)CC2(C(C)C)C3 ICJYJPOGTLSWBN-UHFFFAOYSA-N 0.000 description 1
- KAQDREXRTIUTKK-UHFFFAOYSA-N 3,5-dibutyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC1(CCCC)CC2(CCCC)C3 KAQDREXRTIUTKK-UHFFFAOYSA-N 0.000 description 1
- OCNRWOKQFKXZGR-UHFFFAOYSA-N 3,5-dicyclohexyladamantan-1-amine Chemical compound C1C(N)(C2)CC(C3)CC1(C1CCCCC1)CC32C1CCCCC1 OCNRWOKQFKXZGR-UHFFFAOYSA-N 0.000 description 1
- ITAALVOWSKQISP-UHFFFAOYSA-N 3,5-diethyl-7-methyladamantan-1-amine Chemical compound C1C(C2)(C)CC3(N)CC1(CC)CC2(CC)C3 ITAALVOWSKQISP-UHFFFAOYSA-N 0.000 description 1
- MAQDODRYDKZRSA-UHFFFAOYSA-N 3,5-dihexyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC1(CCCCCC)CC2(CCCCCC)C3 MAQDODRYDKZRSA-UHFFFAOYSA-N 0.000 description 1
- QWBQEEKAKVRBIF-UHFFFAOYSA-N 3,5-dipentyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC1(CCCCC)CC2(CCCCC)C3 QWBQEEKAKVRBIF-UHFFFAOYSA-N 0.000 description 1
- WPXLJHZRYJANCQ-UHFFFAOYSA-N 3,5-diphenyladamantan-1-amine Chemical compound C1C(N)(C2)CC(C3)CC1(C=1C=CC=CC=1)CC32C1=CC=CC=C1 WPXLJHZRYJANCQ-UHFFFAOYSA-N 0.000 description 1
- RBLRBILRVQBSIG-UHFFFAOYSA-N 3-butyl-5-cyclohexyladamantan-1-amine Chemical compound C1C(CCCC)(C2)CC(C3)CC1(N)CC32C1CCCCC1 RBLRBILRVQBSIG-UHFFFAOYSA-N 0.000 description 1
- DEIFIQCDTVHYOV-UHFFFAOYSA-N 3-butyl-5-ethyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CC)CC1(CCCC)C3 DEIFIQCDTVHYOV-UHFFFAOYSA-N 0.000 description 1
- OLXPDDYSCPPKAV-UHFFFAOYSA-N 3-butyl-5-hexyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCCC)CC1(CCCCCC)C3 OLXPDDYSCPPKAV-UHFFFAOYSA-N 0.000 description 1
- TXZQKDJQUVYBAV-UHFFFAOYSA-N 3-butyl-5-methyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(N)CC1(CCCC)C3 TXZQKDJQUVYBAV-UHFFFAOYSA-N 0.000 description 1
- DMYFHACLIMYSRB-UHFFFAOYSA-N 3-butyl-5-pentyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCCC)CC1(CCCCC)C3 DMYFHACLIMYSRB-UHFFFAOYSA-N 0.000 description 1
- HJFLKCNNMZSALM-UHFFFAOYSA-N 3-butyl-5-phenyladamantan-1-amine Chemical compound C1C(CCCC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 HJFLKCNNMZSALM-UHFFFAOYSA-N 0.000 description 1
- QARLESAFJAGAIO-UHFFFAOYSA-N 3-butyl-5-propyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCC)CC1(CCCC)C3 QARLESAFJAGAIO-UHFFFAOYSA-N 0.000 description 1
- KUNFZDMYUIQERL-UHFFFAOYSA-N 3-butyladamantan-1-amine Chemical compound C1C(C2)CC3CC2(N)CC1(CCCC)C3 KUNFZDMYUIQERL-UHFFFAOYSA-N 0.000 description 1
- QPSPKNCPWYOZOQ-UHFFFAOYSA-N 3-cyclohexyl-5-ethyladamantan-1-amine Chemical compound C1C(CC)(C2)CC(C3)CC1(N)CC32C1CCCCC1 QPSPKNCPWYOZOQ-UHFFFAOYSA-N 0.000 description 1
- BEUDGYXRWYAKAG-UHFFFAOYSA-N 3-cyclohexyl-5-hexyladamantan-1-amine Chemical compound C1C(CCCCCC)(C2)CC(C3)CC1(N)CC32C1CCCCC1 BEUDGYXRWYAKAG-UHFFFAOYSA-N 0.000 description 1
- XWSMYWOEEAGQCR-UHFFFAOYSA-N 3-cyclohexyl-5-methyladamantan-1-amine Chemical compound C1C(C)(C2)CC(C3)CC1(N)CC32C1CCCCC1 XWSMYWOEEAGQCR-UHFFFAOYSA-N 0.000 description 1
- IFCVAKRZRKACNB-UHFFFAOYSA-N 3-cyclohexyl-5-pentyladamantan-1-amine Chemical compound C1C(CCCCC)(C2)CC(C3)CC1(N)CC32C1CCCCC1 IFCVAKRZRKACNB-UHFFFAOYSA-N 0.000 description 1
- GECBZEYAMKSLFJ-UHFFFAOYSA-N 3-cyclohexyl-5-phenyladamantan-1-amine Chemical compound C1C(N)(C2)CC(C3)CC1(C1CCCCC1)CC32C1=CC=CC=C1 GECBZEYAMKSLFJ-UHFFFAOYSA-N 0.000 description 1
- BOBKSKBPCSEMON-UHFFFAOYSA-N 3-cyclohexyl-5-propyladamantan-1-amine Chemical compound C1C(CCC)(C2)CC(C3)CC1(N)CC32C1CCCCC1 BOBKSKBPCSEMON-UHFFFAOYSA-N 0.000 description 1
- XUONURYAKCELNT-UHFFFAOYSA-N 3-cyclohexyladamantan-1-amine;hydrochloride Chemical compound Cl.C1C(N)(C2)CC(C3)CC1CC32C1CCCCC1 XUONURYAKCELNT-UHFFFAOYSA-N 0.000 description 1
- WHQKNPQELALARV-UHFFFAOYSA-N 3-ethyl-5-hexyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CC)CC1(CCCCCC)C3 WHQKNPQELALARV-UHFFFAOYSA-N 0.000 description 1
- ZWHAFHCGBIKBIF-UHFFFAOYSA-N 3-ethyl-5-methyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(N)CC1(CC)C3 ZWHAFHCGBIKBIF-UHFFFAOYSA-N 0.000 description 1
- GAWKCQRMGQRNML-UHFFFAOYSA-N 3-ethyl-5-pentyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CC)CC1(CCCCC)C3 GAWKCQRMGQRNML-UHFFFAOYSA-N 0.000 description 1
- ZUTXTLRAGKYACK-UHFFFAOYSA-N 3-ethyl-5-propyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CC)CC1(CCC)C3 ZUTXTLRAGKYACK-UHFFFAOYSA-N 0.000 description 1
- LOPRUTAJASQIDA-UHFFFAOYSA-N 3-hexyl-5-methyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(N)CC1(CCCCCC)C3 LOPRUTAJASQIDA-UHFFFAOYSA-N 0.000 description 1
- URZNPFBAGSZRJP-UHFFFAOYSA-N 3-hexyl-5-pentyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCCCC)CC1(CCCCCC)C3 URZNPFBAGSZRJP-UHFFFAOYSA-N 0.000 description 1
- ODVDRMCIFBNGSW-UHFFFAOYSA-N 3-hexyl-5-phenyladamantan-1-amine Chemical compound C1C(CCCCCC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 ODVDRMCIFBNGSW-UHFFFAOYSA-N 0.000 description 1
- UPBDDXAQCQQAAJ-UHFFFAOYSA-N 3-hexyl-5-propyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCC)CC1(CCCCCC)C3 UPBDDXAQCQQAAJ-UHFFFAOYSA-N 0.000 description 1
- NRHDSAUGPAWDPU-UHFFFAOYSA-N 3-hexyladamantan-1-amine Chemical compound C1C(C2)CC3CC2(N)CC1(CCCCCC)C3 NRHDSAUGPAWDPU-UHFFFAOYSA-N 0.000 description 1
- PMPXWFMKLVAEFO-UHFFFAOYSA-N 3-methyl-5-pentyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(N)CC1(CCCCC)C3 PMPXWFMKLVAEFO-UHFFFAOYSA-N 0.000 description 1
- NMLWLANWDKUOBD-UHFFFAOYSA-N 3-methyl-5-phenyladamantan-1-amine Chemical compound C1C(C)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 NMLWLANWDKUOBD-UHFFFAOYSA-N 0.000 description 1
- NLRUYIOCMXWZSA-UHFFFAOYSA-N 3-methyl-5-propyladamantan-1-amine Chemical compound C1C(C2)CC3(C)CC2(N)CC1(CCC)C3 NLRUYIOCMXWZSA-UHFFFAOYSA-N 0.000 description 1
- XBBCQVZVUGJABN-UHFFFAOYSA-N 3-pentyl-5-phenyladamantan-1-amine Chemical compound C1C(CCCCC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 XBBCQVZVUGJABN-UHFFFAOYSA-N 0.000 description 1
- UJFMDHQWICLPDF-UHFFFAOYSA-N 3-pentyl-5-propyladamantan-1-amine Chemical compound C1C(C2)CC3(N)CC2(CCC)CC1(CCCCC)C3 UJFMDHQWICLPDF-UHFFFAOYSA-N 0.000 description 1
- NTGFIYWWLVZQPT-UHFFFAOYSA-N 3-pentyladamantan-1-amine Chemical compound C1C(C2)CC3CC2(N)CC1(CCCCC)C3 NTGFIYWWLVZQPT-UHFFFAOYSA-N 0.000 description 1
- ZHUNEHAFDUSIHE-UHFFFAOYSA-N 3-phenyl-5-propyladamantan-1-amine Chemical compound C1C(CCC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 ZHUNEHAFDUSIHE-UHFFFAOYSA-N 0.000 description 1
- VCZOJIYQTDUXBF-UHFFFAOYSA-N 3-phenyladamantan-1-amine;hydrochloride Chemical compound Cl.C1C(N)(C2)CC(C3)CC1CC32C1=CC=CC=C1 VCZOJIYQTDUXBF-UHFFFAOYSA-N 0.000 description 1
- QNYZSAKFAQDNGK-UHFFFAOYSA-N 3-phenyladamantan-1-ol Chemical compound C1C(O)(C2)CC(C3)CC1CC32C1=CC=CC=C1 QNYZSAKFAQDNGK-UHFFFAOYSA-N 0.000 description 1
- UNZLVAUDWGXALA-UHFFFAOYSA-N 3-propan-2-yladamantan-1-amine Chemical compound C1C(C2)CC3CC2(N)CC1(C(C)C)C3 UNZLVAUDWGXALA-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KWPYQZKUNOQNKS-UHFFFAOYSA-N Cl.C1C(CC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 Chemical compound Cl.C1C(CC)(C2)CC(C3)CC1(N)CC32C1=CC=CC=C1 KWPYQZKUNOQNKS-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 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
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 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
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- CHHJDCVKYCVTHD-UHFFFAOYSA-N chloromethyl formate Chemical compound ClCOC=O CHHJDCVKYCVTHD-UHFFFAOYSA-N 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000007512 neuronal protection Effects 0.000 description 1
- 230000036963 noncompetitive effect Effects 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
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001292 preischemic effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- 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
- A61P25/28—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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/38—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP89106657.3 | 1989-04-14 | ||
| EP89106657A EP0392059B1 (de) | 1989-04-14 | 1989-04-14 | Verwendung von Adamantan-Derivaten zur Prävention und Behandlung der cerebralen Ischämie |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02292214A JPH02292214A (ja) | 1990-12-03 |
| JP2821233B2 true JP2821233B2 (ja) | 1998-11-05 |
Family
ID=8201228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2099117A Expired - Lifetime JP2821233B2 (ja) | 1989-04-14 | 1990-04-13 | 脳乏血の予防ならびに治療におけるアダマンタン誘導体 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5061703A (show.php) |
| EP (1) | EP0392059B1 (show.php) |
| JP (1) | JP2821233B2 (show.php) |
| AT (1) | ATE94384T1 (show.php) |
| CA (1) | CA2014453C (show.php) |
| CH (1) | CH679208A5 (show.php) |
| DD (1) | DD293493A5 (show.php) |
| DE (2) | DE10299048I2 (show.php) |
| DK (1) | DK173356B1 (show.php) |
| ES (1) | ES2059602T3 (show.php) |
| HU (1) | HU215592B (show.php) |
| IE (1) | IE63467B1 (show.php) |
| LU (1) | LU90988I2 (show.php) |
| NL (1) | NL300107I2 (show.php) |
| PT (1) | PT93763B (show.php) |
| SE (1) | SE9001329L (show.php) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008010481A1 (en) | 2006-07-18 | 2008-01-24 | Astellas Pharma Inc. | Aminoindan derivative or salt thereof |
Families Citing this family (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506231A (en) * | 1989-03-31 | 1996-04-09 | The Children's Medical Center Corporation | Treatment of aids dementia, myelopathy and blindness |
| US5334618A (en) * | 1991-04-04 | 1994-08-02 | The Children's Medical Center Corporation | Method of preventing NMDA receptor-mediated neuronal damage |
| US5455279A (en) * | 1991-04-19 | 1995-10-03 | The Children's Medical Center Corporation | Regimen method of mediating neuronal damage using nitroglycerine |
| US5614560A (en) * | 1991-04-04 | 1997-03-25 | Children's Medical Center Corporation | Method of preventing NMDA receptor-mediated neuronal damage |
| WO1992017168A1 (en) * | 1991-04-04 | 1992-10-15 | The Children's Medical Center Corporation | Method of preventing nmda receptor-mediated neuronal damage |
| DE4225730C2 (de) * | 1992-08-04 | 2003-04-30 | Merz Pharma Gmbh & Co Kgaa | Verfahren zur Herstellung von festen Arzneiformkörpern mit protrahierter 2-Stufen-Freisetzung |
| IL112099A (en) * | 1993-12-23 | 1999-07-14 | Ortho Pharma Corp | N-oxides of 4-arylpiperazines and 4-arylpiperidines and pharmaceutical compositions containing them |
| DE19510189A1 (de) * | 1995-03-21 | 1996-09-26 | Hartmut Dr Goebel | Verwendung von Amantadin |
| DE19528388A1 (de) * | 1995-08-02 | 1997-02-06 | Hans Peter Prof Dr Med Zenner | Verwendung von Adamantan-Derivaten zur Behandlung von Erkrankungen des Innenohrs |
| US6057373A (en) * | 1997-05-22 | 2000-05-02 | Synchroneuron, Llc | Methods of treating tardive dyskinesia and other movement disorders using NMDA receptor antagonists |
| US5866585A (en) * | 1997-05-22 | 1999-02-02 | Synchroneuron, Llc | Methods of treating tardive dyskinesia using NMDA receptor antagonists |
| US5952389A (en) * | 1998-01-13 | 1999-09-14 | Synchroneuron | Methods of treating tardive dyskinesia and other movement disorders |
| US6294583B1 (en) | 1998-01-13 | 2001-09-25 | Synchroneuron, Llc | Methods of treating tardive dyskinesia and other movement disorders |
| GB9802225D0 (en) * | 1998-02-02 | 1998-04-01 | Cerebrus Ltd | Chemical compounds |
| RU2147573C1 (ru) * | 1998-08-24 | 2000-04-20 | Волгоградский государственный технический университет | Способ получения адамант-1-иламина и его производных |
| US6444702B1 (en) * | 2000-02-22 | 2002-09-03 | Neuromolecular, Inc. | Aminoadamantane derivatives as therapeutic agents |
| US20040122090A1 (en) * | 2001-12-07 | 2004-06-24 | Lipton Stuart A. | Methods for treating neuropsychiatric disorders with nmda receptor antagonists |
| US7795468B2 (en) * | 2001-01-19 | 2010-09-14 | Chevron U.S.A. Inc. | Functionalized higher diamondoids |
| US20040248984A1 (en) * | 2001-08-29 | 2004-12-09 | Josef Krieglstein | Use of $g(b)-adrenoceptor agonists for the treatment of neurodegenerative diseases |
| AU2002333510A1 (en) | 2001-08-29 | 2003-03-18 | Eucro European Contract Research Gmbh And Co. Kg | Use of beta-adrenoceptor agonists for the treatment of neurodegenerative diseases |
| DE10142176A1 (de) * | 2001-08-29 | 2003-03-27 | Eucro Europe Contract Res Gmbh | Verwendung einer Kombination aus ß-adrenergen Agonisten und NDMA-Antagonisten |
| GB0202161D0 (en) * | 2002-01-30 | 2002-03-20 | Vernalis Res Ltd | Chemical compounds V |
| AU2003251993A1 (en) * | 2002-07-19 | 2004-02-09 | Inge Grundke-Iqbal | NMDA RECEPTOR ANTAGONISTS AND THEIR USE IN INHIBITING ABNORMAL HYPERPHOSPHORYLATION OF MICROTUBULE ASSOCIATED PROTEIN tau |
| UA83645C2 (ru) | 2002-10-24 | 2008-08-11 | Мерц Фарма Гмбх Унд Ко. Кгаа | Фармацевтический продукт, который содержит производное 1-аминоциклогексана и ингибитор ацетилхолинестеразы, его применение |
| RU2246482C2 (ru) * | 2002-12-25 | 2005-02-20 | ООО "Циклан" | Способ получения гидрохлорида 1-амино-3,5-диметиладамантана |
| CN1794981A (zh) | 2003-05-27 | 2006-06-28 | 森林实验室公司 | 治疗抑郁症和其它情绪障碍的nmda受体拮抗剂和选择性5－羟色胺重摄取抑制剂的组合 |
| CN100345819C (zh) * | 2003-07-01 | 2007-10-31 | 北京德众万全药物技术开发有限公司 | 一种取代的金刚烷胺类化合物或其盐的制备方法 |
| ITTO20030668A1 (it) * | 2003-09-02 | 2005-03-03 | Rotta Res Lab S P A O Ra Rottapharm | Derivati dell'adamantano dotati di attivita' neuroprotettiva, antidepressiva e anti-ischemica e procedimento per la loro preparazione. |
| CN1240668C (zh) * | 2003-09-10 | 2006-02-08 | 上海医药工业研究院 | 一种新的盐酸美金刚制备方法 |
| CN1870984A (zh) * | 2003-10-22 | 2006-11-29 | 莫茨药物股份两合公司 | 1－氨基环己烷衍生物用于调节淀粉样病变中原纤维生成Aβ肽的沉积的用途 |
| AR046314A1 (es) | 2003-11-05 | 2005-11-30 | Merz Pharma Gmbh & Co Kgaa | Composiciones que comprenden ciclohexilaminas y aminoadamantanos |
| UY28650A1 (es) * | 2003-12-05 | 2005-02-28 | Forest Laboratories | Memantina para la prevencion o disminucion de la conducta suicida y para el tratamiento de la depresion mayor asociada con esta conducta |
| RS51540B (sr) * | 2004-01-05 | 2011-06-30 | Merz Pharma Gmbh. & Co. Kgaa. | Memantin za lečenje blage do umerene alzhajmerove bolesti |
| WO2005072705A1 (en) * | 2004-01-29 | 2005-08-11 | Neuromolecular, Inc. | Combination of a nmda receptor antagonist and a mao-inhibitor or a gadpf-inhibitor for the treatment of central nervous system-related conditions |
| US7456224B2 (en) * | 2004-04-05 | 2008-11-25 | Forest Laboratories Holdings, Ltd. | Method for treating autism |
| US20060002999A1 (en) * | 2004-06-17 | 2006-01-05 | Forest Laboratories, Inc. | Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane |
| EP1781261A1 (en) * | 2004-06-17 | 2007-05-09 | Forest Laboratories, Inc. | Modified release formulation of memantine |
| CN101389315A (zh) | 2004-06-17 | 2009-03-18 | 莫茨药物股份两合公司 | 美金刚口服剂型即释制剂 |
| TW200616608A (en) * | 2004-07-09 | 2006-06-01 | Forest Laboratories | Memantine as adjunctive treatment to atypical antipsychotics in schizophrenia patients |
| TW200621677A (en) * | 2004-09-21 | 2006-07-01 | Astellas Pharma Inc | Cyclic amine derivative or salt thereof |
| MX2007003267A (es) * | 2004-09-23 | 2007-05-23 | Merz Pharma Gmbh & Co Kgaa | Memantina para el tratamiento de trastornos de conducta en la infancia. |
| CN100351225C (zh) * | 2004-10-28 | 2007-11-28 | 中国医学科学院医药生物技术研究所 | 一组金刚烷胺类衍生物及其合成方法和作为神经元损伤保护剂的应用 |
| EP1827385B1 (en) | 2004-11-23 | 2013-03-27 | Adamas Pharmaceuticals, Inc. | Pharmaceutical composition comprising memantine in an extended dosage release form for use in the treatment of dementias |
| US7619007B2 (en) * | 2004-11-23 | 2009-11-17 | Adamas Pharmaceuticals, Inc. | Method and composition for administering an NMDA receptor antagonist to a subject |
| CA2588296A1 (en) | 2004-11-24 | 2006-06-01 | Neuromolecular Pharmaceuticals, Inc. | Composition comprising an nmda receptor antagonist and levodopa and use thereof for treating neurological disease |
| US20060205822A1 (en) * | 2004-12-22 | 2006-09-14 | Forest Laboratories, Inc. | 1-Aminocyclohexane derivatives for the treatment of multiple sclerosis, emotional lability and pseudobulbar affect |
| WO2006076562A1 (en) * | 2005-01-11 | 2006-07-20 | Teva Pharmaceutical Fine Chemicals S.R.L. | Process for the preparation of 1-amino-3,5-dimethyladamantane hydrochloride |
| CA2604052C (en) | 2005-04-06 | 2014-07-08 | Adamas Pharmaceuticals, Inc. | Methods and compositions for the treatment of cns-related conditions |
| ITMI20050833A1 (it) | 2005-05-10 | 2006-11-11 | A M S A S P A Anonima Materie Sintetiche Affini | Nuovo procedimento per la sintesi di aminoadamantani |
| EP1879849A1 (en) * | 2005-05-11 | 2008-01-23 | Dr. Reddy's Laboratories, Inc. | Process for preparing memantine |
| EA013474B1 (ru) * | 2005-06-16 | 2010-04-30 | Форест Лэборэтериз, Инк. | Композиция в виде гранул с модифицированным и немедленным высвобождением мемантина |
| CA2612338C (en) | 2005-06-17 | 2015-02-03 | Apogee Biotechnology Corporation | Sphingosine kinase inhibitors |
| RU2309940C2 (ru) * | 2005-09-30 | 2007-11-10 | НПЦ "Фармзащита" | Способ получения 3,5-диметиладамантил-1-амина или его солей |
| US20070099947A1 (en) * | 2005-11-03 | 2007-05-03 | Alkermes, Inc. | Methods and compositions for the treatment of brain reward system disorders by combination therapy |
| ATE541827T1 (de) | 2006-02-21 | 2012-02-15 | Hexal Ag | Verfahren zur herstellung von adamantanaminen |
| DE102006009279A1 (de) | 2006-03-01 | 2007-09-06 | Justus-Liebig-Universität Giessen | Verfahren zur Herstellung von 1-Formamido-3,5-dimethyladamantan |
| DE102006009278B4 (de) * | 2006-03-01 | 2010-06-02 | Justus-Liebig-Universität Giessen | Verfahren zur direkten Formamidierung oder Acetamidierung von Admantan und Admantanderivaten sowie deren Verwendung zur Herstellung von Aminoadmantanen |
| CA2644819A1 (en) | 2006-03-27 | 2007-11-08 | Teva Pharmaceutical Fine Chemicals S.R.L. | Process for preparing memantine hydrochloride substantially free of impurities |
| WO2008002594A2 (en) * | 2006-06-27 | 2008-01-03 | Neuroprotection For Life Corp. | Neuronal circuit-dependent neuroprotection by interaction between nicotinic receptors |
| WO2008005534A2 (en) * | 2006-07-06 | 2008-01-10 | Forest Laboratories, Inc. | Orally dissolving formulations of memantine |
| MX2009001036A (es) | 2006-08-04 | 2009-04-23 | Merz Pharma Gmbh & Co Kgaa | Pirazolopirimidinas, proceso para su preparacion y su uso como medicina. |
| WO2008062472A2 (en) * | 2006-10-24 | 2008-05-29 | Cadila Healthcare Limited | Process for the preparation of memantine |
| EP2420235A1 (en) | 2006-10-27 | 2012-02-22 | Medivation Neurology, Inc. | Methods and combination therapies for treating alzheimer's disease |
| WO2008063847A2 (en) * | 2006-11-03 | 2008-05-29 | Forest Laboratories Holdings Limited | Method for treating autism |
| GB0623897D0 (en) * | 2006-11-30 | 2007-01-10 | Pliva Istrazivanje I Razvoj D | Pharmaceutical composition of memantine |
| US20080182908A1 (en) * | 2007-01-25 | 2008-07-31 | Vinita Umashankar Vyas | Pharmaceutical compositions comprising memantine |
| EP2085398A1 (en) | 2008-02-01 | 2009-08-05 | Merz Pharma GmbH & Co. KGaA | Pyrazolopyrimidines, a process for their preparation and their use as medicine |
| EP2090576A1 (en) | 2008-02-01 | 2009-08-19 | Merz Pharma GmbH & Co.KGaA | 6-halo-pyrazolo[1,5-a]pyridines, a process for their preparation and their use as metabotropic glutamate receptor (mGluR) modulators |
| EP2265114A4 (en) * | 2008-03-13 | 2012-04-25 | Univ California | USE OF EPICATECHIN AND ITS DERIVATIVES AND SALTS FOR THE PROTECTION OF THE HEART AGAINST ISCHEMIC MYOKARD AND FOR THE IMPROVEMENT OF CARDIAL REMODELING |
| EP2274276B1 (en) * | 2008-03-20 | 2014-07-09 | Merz Pharma GmbH & Co. KGaA | Process for the manufacture of memantine and intermediate product |
| EP2103597A1 (en) | 2008-03-20 | 2009-09-23 | Merz Pharma GmbH & Co.KGaA | Process for the manufacture of memantine and intermediate product |
| KR100998525B1 (ko) * | 2008-03-28 | 2010-12-07 | 나노다이아몬드 주식회사 | 아밀로이드 올리고머 독성 억제제로서의 아다만탄 유도체 |
| US20090247644A1 (en) * | 2008-03-28 | 2009-10-01 | Forest Laboratories Holdings Limited | Memantine formulations |
| EP2288345B1 (en) | 2008-04-18 | 2015-06-10 | University College Dublin National University Of Ireland, Dublin | Psycho-pharmaceuticals |
| EP2111858A1 (en) | 2008-04-25 | 2009-10-28 | EPFL Ecole Polytechnique Fédérale de Lausanne | Novel treatment for alzheimer's disease |
| US20090275597A1 (en) * | 2008-05-02 | 2009-11-05 | Forest Laboratories Holdings Limited | Methods of treating cns disorders |
| EP2138173A1 (en) | 2008-06-26 | 2009-12-30 | Merz Pharma GmbH & Co.KGaA | Pharmaceutical compositions comprising aminoadamantane derivatives |
| UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
| WO2010112221A1 (en) | 2009-04-03 | 2010-10-07 | Synthon B.V. | Pharmaceutical compositions comprising memantine |
| JP5778148B2 (ja) | 2009-08-04 | 2015-09-16 | メルク パテント ゲーエムベーハー | 多環式炭水化物を含む電子デバイス |
| TW201116532A (en) | 2009-08-05 | 2011-05-16 | Merz Pharma Gmbh & Co Kgaa | Metabotropic glutamate receptor modulators |
| CA2994873A1 (en) | 2009-12-02 | 2011-06-09 | Adamas Pharmaceuticals, Inc. | Amantadine compositions and methods of use |
| ES2758554T3 (es) | 2009-12-08 | 2020-05-05 | Univ Case Western Reserve | Aminoácidos gama para tratamiento de trastornos oculares |
| US20110251239A1 (en) | 2010-04-07 | 2011-10-13 | Eisai Inc. | Combination therapy for the treatment of dementia |
| JP5562716B2 (ja) * | 2010-05-12 | 2014-07-30 | 花王株式会社 | 電位依存性カチオンチャネル抑制剤 |
| WO2011147999A1 (es) | 2010-05-24 | 2011-12-01 | Farmalider, S.A. | Compuesto inhibidor de la activación de la enzima erk1/2 para su uso en el tratamiento de enfermedades neurodegenerativas |
| FR2962335B1 (fr) | 2010-07-12 | 2013-01-18 | Cll Pharma | Utilisation du nonapeptide pat dans le traitement et la prevention des maladies neurodegeneratives |
| WO2012048871A1 (en) | 2010-10-12 | 2012-04-19 | Merz Pharma Gmbh & Co. Kgaa | Memantine for improving cognitive performance in subjects |
| AR083475A1 (es) | 2010-10-18 | 2013-02-27 | Merz Pharma Gmbh & Co Kgaa | Moduladores de receptores de glutamato metabotropicos |
| MX2013004760A (es) | 2010-10-29 | 2013-07-02 | Merz Pharma Gmbh & Co Kgaa | Derivados de indol y proceso para su preparacion. |
| EP3034079B1 (en) | 2010-11-15 | 2018-01-10 | Agenebio, Inc. | Pyridazine derivatives, compositions and methods for treating cognitive impairment |
| AR084515A1 (es) | 2010-12-22 | 2013-05-22 | Merz Pharma Gmbh & Co Kgaa | Derivados heterociclicos nitrogenados, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de enfermedades asociadas al sistema nervioso central tales como parkinson y alzheimer, entre otras |
| AR084516A1 (es) | 2010-12-22 | 2013-05-22 | Merz Pharma Gmbh & Co Kgaa | Moduladores de receptores de glutamato metabotropicos |
| US20140004189A1 (en) | 2011-01-25 | 2014-01-02 | Cadila Healthcare Limited | Modified release pharmaceutical compositions memantine |
| CN102241678B (zh) | 2011-04-26 | 2014-10-29 | 辽宁利锋科技开发有限公司 | 含有脂环结构化合物的抗肿瘤作用与应用 |
| WO2012152854A1 (en) | 2011-05-12 | 2012-11-15 | Merz Pharma Gmbh & Co. Kgaa | Metabotropic glutamate receptor modulators |
| WO2012172093A1 (en) | 2011-06-17 | 2012-12-20 | Merz Pharma Gmbh & Co. Kgaa | Dihydroindolizine derivate as metabotropic glutamate receptor modulators |
| EP2650284A1 (en) | 2012-04-10 | 2013-10-16 | Merz Pharma GmbH & Co. KGaA | Heterocyclic derivatives as metabotropic glutamate receptor modulators |
| CN104519886B (zh) | 2012-04-14 | 2017-09-12 | 细胞内治疗公司 | 有机化合物 |
| RU2488388C1 (ru) | 2012-05-24 | 2013-07-27 | Ооо "Валента Интеллект" | Фармацевтическая композиция для профилактики и лечения психических, поведенческих, когнитивных расстройств |
| US9242009B2 (en) | 2012-07-17 | 2016-01-26 | The General Hospital Corporation | Compositions and methods to treat neurodegenerative diseases |
| UA107653U (uk) | 2012-10-01 | 2016-06-24 | Общєство С Огранічєнной Отвєтствєнностью "Валєнта-Інтєллєкт" | Композиція лікарських засобів для лікування та профілактики поведінкових, психічних та когнітивних розладів |
| US10154971B2 (en) | 2013-06-17 | 2018-12-18 | Adamas Pharma, Llc | Methods of administering amantadine |
| CA3123897C (en) | 2013-12-20 | 2024-02-06 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| CA2938671A1 (en) | 2014-02-04 | 2015-08-13 | Forest Laboratories Holdings Limited | Donepezil compositions and method of treating alzheimer's disease |
| IL234638A0 (en) | 2014-09-14 | 2014-12-02 | Yeda Res & Dev | NMDA receptor antagonists for the treatment of Gaucher disease |
| CN108026107B (zh) | 2015-06-19 | 2021-07-30 | 艾吉因生物股份有限公司 | 用于治疗认知损害的苯并二氮杂环庚三烯衍生物、组合物和方法 |
| WO2017093354A1 (en) | 2015-11-30 | 2017-06-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Nmdar antagonists for the treatment of diseases associated with angiogenesis |
| RU2737464C2 (ru) | 2015-12-30 | 2020-11-30 | Кориум Интернэшнл, Инк. | Системы и способы длительного трансдермального введения |
| EP3405183A4 (en) | 2016-01-18 | 2019-12-11 | Arisan Therapeutics Inc. | ADAMATE DERIVATIVES FOR TREATING A FILOVIRUS INFECTION |
| WO2017223402A1 (en) | 2016-06-23 | 2017-12-28 | Corium International, Inc. | Adhesive matrix with hydrophilic and hydrophobic domains and a therapeutic agent |
| KR102508993B1 (ko) | 2016-07-27 | 2023-03-10 | 코리움, 인크. | 메만틴 경피 송달 시스템 |
| AU2017302305A1 (en) | 2016-07-27 | 2019-02-14 | Corium, LLC. | Transdermal delivery systems with pharmacokinetics bioequivalent to oral delivery |
| US20180028463A1 (en) | 2016-07-27 | 2018-02-01 | Corium International Inc. | Transdermal formulation and delivery method of low solubility or unstable unionized neutral drugs by in situ salt-to-neutral drug conversion of salt drug |
| US20180170941A1 (en) | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US11505555B2 (en) | 2016-12-19 | 2022-11-22 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US10369187B2 (en) | 2017-02-09 | 2019-08-06 | Vanderbilt University | Peptide regulators of JNK family kinases |
| US11548893B2 (en) | 2017-07-15 | 2023-01-10 | Arisan Therapeutics Inc. | Enantiomerically pure adamantane carboxamides for the treatment of filovirus infection |
| AU2018392686A1 (en) | 2017-12-20 | 2020-07-09 | Corium Pharma Solutions, Inc. | Transdermal adhesive composition comprising a volatile liquid therapeutic agent having low melting point |
| CN112601749B (zh) | 2018-06-19 | 2024-03-26 | 艾吉因生物股份有限公司 | 用于治疗认知损害的苯并二氮杂环庚三烯衍生物，组合物和方法 |
| WO2020240505A1 (en) | 2019-05-31 | 2020-12-03 | TECNIMEDE - Sociedade Técnico-medicinal, SA | Immediate release fixed-dose combination of memantine and donepezil |
| EP4005565A1 (en) | 2020-11-30 | 2022-06-01 | Merz Pharmaceuticals GmbH | Novel uses of adamantane derivatives |
| US20250161238A1 (en) | 2022-02-08 | 2025-05-22 | Fikret Sahin | NMDAR Antagonists Prevent Ageing and Aging-Associated Conditions and Diseases Through Increasing 20S Proteasome Activity |
| US20240132513A1 (en) | 2022-08-19 | 2024-04-25 | Agenebio, Inc. | Benzazepine derivatives, compositions, and methods for treating cognitive impairment |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3450761A (en) * | 1967-03-30 | 1969-06-17 | Sun Oil Co | 1-aminoethyldimethyladamantane |
| US4748154A (en) * | 1985-12-24 | 1988-05-31 | Takeda Chemical Industries, Ltd. | Peptide derivatives, their production and use |
| IT1205042B (it) * | 1987-05-28 | 1989-03-10 | Crinos Industria Farmaco | Composizione farmaceutica ad attivita' terapeutica per il trattamento della demenza senile di tipo alzheimer |
-
1989
- 1989-04-14 AT AT89106657T patent/ATE94384T1/de active
- 1989-04-14 DE DE2002199048 patent/DE10299048I2/de active Active
- 1989-04-14 ES ES89106657T patent/ES2059602T3/es not_active Expired - Lifetime
- 1989-04-14 DE DE89106657T patent/DE58905637D1/de not_active Expired - Lifetime
- 1989-04-14 EP EP89106657A patent/EP0392059B1/de not_active Expired - Lifetime
-
1990
- 1990-03-16 IE IE99690A patent/IE63467B1/en not_active IP Right Cessation
- 1990-04-10 CH CH1539/90A patent/CH679208A5/de not_active IP Right Cessation
- 1990-04-11 US US07/508,109 patent/US5061703A/en not_active Expired - Lifetime
- 1990-04-11 CA CA002014453A patent/CA2014453C/en not_active Expired - Lifetime
- 1990-04-11 SE SE9001329A patent/SE9001329L/xx not_active Application Discontinuation
- 1990-04-11 DK DK199000916A patent/DK173356B1/da not_active IP Right Cessation
- 1990-04-12 PT PT93763A patent/PT93763B/pt not_active IP Right Cessation
- 1990-04-12 DD DD90339741A patent/DD293493A5/de not_active IP Right Cessation
- 1990-04-13 JP JP2099117A patent/JP2821233B2/ja not_active Expired - Lifetime
- 1990-04-13 HU HU902434A patent/HU215592B/hu unknown
-
2002
- 2002-11-13 LU LU90988C patent/LU90988I2/fr unknown
- 2002-11-14 NL NL300107C patent/NL300107I2/nl unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008010481A1 (en) | 2006-07-18 | 2008-01-24 | Astellas Pharma Inc. | Aminoindan derivative or salt thereof |
| US8013018B2 (en) | 2006-07-18 | 2011-09-06 | Astellas Pharma Inc. | Aminoindane derivative or salt thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| LU90988I2 (fr) | 2003-01-13 |
| NL300107I1 (nl) | 2003-02-03 |
| HU902434D0 (en) | 1990-08-28 |
| HU215592B (hu) | 1999-01-28 |
| EP0392059A1 (de) | 1990-10-17 |
| ATE94384T1 (de) | 1993-10-15 |
| PT93763A (pt) | 1990-11-20 |
| DK91690A (da) | 1990-10-15 |
| IE63467B1 (en) | 1995-04-19 |
| NL300107I2 (nl) | 2003-02-03 |
| SE9001329D0 (sv) | 1990-04-11 |
| HUT58200A (en) | 1992-02-28 |
| IE900996L (en) | 1990-10-14 |
| ES2059602T3 (es) | 1994-11-16 |
| US5061703A (en) | 1991-10-29 |
| DD293493A5 (de) | 1991-09-05 |
| CA2014453A1 (en) | 1990-10-14 |
| EP0392059B1 (de) | 1993-09-15 |
| CH679208A5 (show.php) | 1992-01-15 |
| SE9001329L (sv) | 1990-10-15 |
| JPH02292214A (ja) | 1990-12-03 |
| DE10299048I1 (de) | 2003-03-27 |
| DE10299048I2 (de) | 2006-07-13 |
| DK91690D0 (da) | 1990-04-11 |
| DE58905637D1 (de) | 1993-10-21 |
| CA2014453C (en) | 2000-03-28 |
| DK173356B1 (da) | 2000-08-07 |
| PT93763B (pt) | 1996-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2821233B2 (ja) | 脳乏血の予防ならびに治療におけるアダマンタン誘導体 | |
| DE69912313T2 (de) | Colchinolderivate als gefässschädigende mittel | |
| JP2001010953A (ja) | ２，４−ジスルホフェニルブチルニトロン、その塩および薬学的スピントラップ剤としてのそれらの使用 | |
| JPH09511506A (ja) | ステロイドホルモン及びその拮抗薬の永久的イオン性誘導体 | |
| JP5399564B2 (ja) | トラマドールとコキシブとの共結晶 | |
| JPH04244024A (ja) | 痴呆及び脳血管障害予防・治療剤並びに血小板凝集抑制剤 | |
| EP1127045B1 (en) | Triphenylbutene derivatives for the treatment of neurological disorders | |
| JP2016512526A (ja) | オナプリストン多形体及び使用方法 | |
| US5049555A (en) | Antagonists of specific excitatory amino acid receptors as neuroprotectants and anxiolytics | |
| US6258807B1 (en) | Method for treating pain | |
| US6335371B1 (en) | Method for inducing cognition enhancement | |
| CN108239095A (zh) | 一类吡喃并咔唑生物碱及其制备方法和其药物组合物与用途 | |
| AU2017216288B2 (en) | Novel combinatorial therapies of neurological disorders | |
| CN113546082A (zh) | 特拉匹韦在制备治疗缺血/再灌注损伤的药物及细胞保护药物中的应用 | |
| CA3252370A1 (en) | PREVENTION OR TREATMENT OF CARDIOVASCULAR DISEASES USING ASPIRIN AND OTHER HIGHLY PENETRATING NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) | |
| CN110267661A (zh) | 包括trh类似物和丙基辛酸的组合的组合物和丙基辛酸的药学上可接受的盐 | |
| EP2488169A1 (en) | Co-crystals of tramadol and coxibs | |
| CN113975276A (zh) | 考比替尼在制备治疗缺血/再灌注损伤药物及细胞保护药物中的应用 | |
| US20030022889A1 (en) | Method for providing neuro-protective effects | |
| WO2000027807A1 (en) | Polymorphic forms of an amyloidosis inhibitor and methods of preparation | |
| EP0872238B1 (en) | Use of olanzapine for the manufacture of a medicament for neuroprotection | |
| EP3411025A1 (en) | Novel combinatorial therapies of neurological disorders | |
| JPS63295579A (ja) | 骨粗鬆症治療剤 | |
| WO2010142642A1 (en) | 4 -hydrazono- 1,4 -dihydropyridine derivatives for the treatment of neurodegenerative diseases | |
| MXPA98007808A (en) | Use of olanzapine to treat the do |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20080828 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20080828 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090828 Year of fee payment: 11 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090828 Year of fee payment: 11 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100828 Year of fee payment: 12 |
|
| EXPY | Cancellation because of completion of term | ||
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100828 Year of fee payment: 12 |