LU88248A1 - Derives de l'indole - Google Patents
Derives de l'indole Download PDFInfo
- Publication number
- LU88248A1 LU88248A1 LU88248A LU88248A LU88248A1 LU 88248 A1 LU88248 A1 LU 88248A1 LU 88248 A LU88248 A LU 88248A LU 88248 A LU88248 A LU 88248A LU 88248 A1 LU88248 A1 LU 88248A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- compound
- compound according
- metabolically labile
- formula
- salt
- Prior art date
Links
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 9
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 24
- 150000002148 esters Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 10
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 9
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 230000002461 excitatory amino acid Effects 0.000 claims description 8
- 239000003257 excitatory amino acid Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical class C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- -1 alkaline earth metal salts Chemical class 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 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 6
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
- 150000002475 indoles Chemical class 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 229960001681 croscarmellose sodium Drugs 0.000 description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- BAMUEXIPKSRTBS-UHFFFAOYSA-N 1,1-dichloro-1,2,2,2-tetrafluoroethane Chemical compound FC(F)(F)C(F)(Cl)Cl BAMUEXIPKSRTBS-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 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 2
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 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 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-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
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 2
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000005809 transesterification reaction Methods 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 229940029284 trichlorofluoromethane Drugs 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- LORJLEXVRAHTFL-UHFFFAOYSA-N (2-anilino-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1NC(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LORJLEXVRAHTFL-UHFFFAOYSA-N 0.000 description 1
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
- BDXZOJVMTJOAPS-UHFFFAOYSA-N (3,5-dichlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC(Cl)=CC(Cl)=C1 BDXZOJVMTJOAPS-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WZBNEZWCNKUOSM-UHFFFAOYSA-N 3-(3-anilino-3-oxoprop-1-enyl)-4,6-dichloro-1H-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C=CC(=O)NC1=CC=CC=C1 WZBNEZWCNKUOSM-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-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
- 206010012289 Dementia Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 1
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 206010028923 Neonatal asphyxia Diseases 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- DGXMYSHVJMOWMA-UHFFFAOYSA-N ethyl 3-(3-anilino-3-oxoprop-1-enyl)-4,6-dichloro-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C=CC(=O)NC1=CC=CC=C1 DGXMYSHVJMOWMA-UHFFFAOYSA-N 0.000 description 1
- NFILHPVBZNKVNP-UHFFFAOYSA-N ethyl 4,6-dichloro-3-formyl-1h-indole-2-carboxylate Chemical compound ClC1=CC(Cl)=C2C(C=O)=C(C(=O)OCC)NC2=C1 NFILHPVBZNKVNP-UHFFFAOYSA-N 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000015362 glutaric aciduria Diseases 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000001057 ionotropic effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- BMQVDVJKPMGHDO-UHFFFAOYSA-K magnesium;potassium;chloride;sulfate;trihydrate Chemical compound O.O.O.[Mg+2].[Cl-].[K+].[O-]S([O-])(=O)=O BMQVDVJKPMGHDO-UHFFFAOYSA-K 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9208492 | 1992-04-16 | ||
| GB929208492A GB9208492D0 (en) | 1992-04-16 | 1992-04-16 | Heterocyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU88248A1 true LU88248A1 (fr) | 1994-03-01 |
Family
ID=10714220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU88248A LU88248A1 (fr) | 1992-04-16 | 1993-04-15 | Derives de l'indole |
Country Status (41)
| Country | Link |
|---|---|
| US (4) | US5374648A (sv) |
| EP (1) | EP0568136A1 (sv) |
| JP (2) | JPH07505407A (sv) |
| KR (1) | KR100264114B1 (sv) |
| CN (1) | CN1042331C (sv) |
| AP (1) | AP480A (sv) |
| AT (1) | AT403917B (sv) |
| AU (1) | AU666927B2 (sv) |
| BE (1) | BE1006343A5 (sv) |
| BG (1) | BG62136B1 (sv) |
| BR (1) | BR1100323A (sv) |
| CA (3) | CA2094073A1 (sv) |
| CH (1) | CH685630A5 (sv) |
| CY (1) | CY2038B1 (sv) |
| CZ (1) | CZ285799B6 (sv) |
| DK (1) | DK169890B1 (sv) |
| ES (1) | ES2105924B1 (sv) |
| FI (1) | FI106198B (sv) |
| FR (1) | FR2690919B1 (sv) |
| GB (2) | GB9208492D0 (sv) |
| GE (1) | GEP19991704B (sv) |
| GR (1) | GR1001619B (sv) |
| HK (1) | HK95797A (sv) |
| HU (2) | HU217964B (sv) |
| IL (1) | IL105412A (sv) |
| IS (1) | IS3994A (sv) |
| IT (1) | IT1265325B1 (sv) |
| LU (1) | LU88248A1 (sv) |
| MX (1) | MX9302195A (sv) |
| MY (1) | MY112232A (sv) |
| NO (1) | NO301879B1 (sv) |
| NZ (1) | NZ247413A (sv) |
| OA (1) | OA10103A (sv) |
| PL (1) | PL176451B1 (sv) |
| RO (1) | RO113242B1 (sv) |
| RU (1) | RU2129544C1 (sv) |
| SE (1) | SE504336C2 (sv) |
| SK (1) | SK281941B6 (sv) |
| TW (1) | TW224457B (sv) |
| WO (1) | WO1993021153A1 (sv) |
| ZA (1) | ZA932642B (sv) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9304500D0 (en) * | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| US5519048A (en) * | 1993-05-27 | 1996-05-21 | Merrell Pharmaceuticals Inc. | 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof |
| JP3334805B2 (ja) * | 1993-05-27 | 2002-10-15 | メレルファーマスーティカルズ インコーポレイテッド | ３−（インドール−３−イル）−プロペン酸誘導体類及びその製剤組成物 |
| GB9319243D0 (en) * | 1993-09-17 | 1993-11-03 | Glaxo Spa | Heterocyclic compounds |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| TW280819B (sv) * | 1993-11-17 | 1996-07-11 | Sumitomo Pharma | |
| US5563157B1 (en) * | 1994-10-31 | 1999-02-02 | Hoecst Marion Roussel Inc | Heterocycle substituted propenoic acid derivatives and pharmaceutical compositions thereof |
| GB9502695D0 (en) * | 1995-02-11 | 1995-03-29 | Glaxo Spa | Pharmaceutical composition |
| GB9504361D0 (en) * | 1995-03-04 | 1995-04-26 | Glaxo Spa | Heterocyclic compounds |
| US6030968A (en) * | 1996-09-17 | 2000-02-29 | The Regents Of The University Of California | Positive AMPA receptor modulation to enhance brain neurotrophic factor expression |
| DE69734594T2 (de) * | 1996-09-30 | 2006-07-06 | Aventis Pharmaceuticals Inc. | Nmda (n-methyl-d-aspartate) antagonists |
| US5922752A (en) * | 1997-06-11 | 1999-07-13 | Hoechst Marion Roussell, Inc. | NMDA (n-methyl-d-aspartate) antagonists |
| ES2367294T3 (es) * | 1998-03-26 | 2011-11-02 | Astellas Pharma Inc. | Preparación de liberación sostenida de un compuesto macrólido como tacrolimus. |
| US20030162825A1 (en) * | 2001-11-09 | 2003-08-28 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| CA2468544A1 (en) * | 2001-12-10 | 2003-06-19 | Amgen Inc. | Vanilloid receptor ligands |
| PA8579701A1 (es) * | 2002-08-23 | 2005-05-24 | Pfizer Prod Inc | Profarmaco inhibidor de beta-lactamasa |
| DE10306202A1 (de) * | 2003-02-13 | 2004-08-26 | Grünenthal GmbH | Arzneimittel enthaltend substituierte 2-Aryl-Aminoessigsäure-Verbindungen und/oder substituierte 2-Heteroaryl-Aminoessigsäure-Verbindungen |
| WO2004108733A1 (en) * | 2003-06-05 | 2004-12-16 | Pfizer Products Inc. | Beta-lactamase inhibitor prodrug |
| WO2005051919A1 (en) * | 2003-11-26 | 2005-06-09 | Pfizer Products Inc. | Aminopyrazole derivatives as gsk-3 inhibitors |
| US7488747B2 (en) * | 2003-12-29 | 2009-02-10 | Sepracor Inc. | Pyrrole and pyrazole DAAO inhibitors |
| US20060002999A1 (en) * | 2004-06-17 | 2006-01-05 | Forest Laboratories, Inc. | Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane |
| AU2006264317B2 (en) | 2005-07-06 | 2012-02-23 | Sunovion Pharmaceuticals Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
| ES2594156T3 (es) * | 2006-01-06 | 2016-12-16 | Sunovion Pharmaceuticals Inc. | Cicloalquilaminas como inhibidores de la recaptación de monoaminas |
| CN101426372A (zh) * | 2006-01-06 | 2009-05-06 | 塞普拉柯公司 | 基于四氢萘酮的单胺再摄取抑制剂 |
| US8097760B2 (en) | 2006-03-31 | 2012-01-17 | Sunovion Pharmacuticals Inc. | Preparation of chiral amides and amines |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
| EP1942104A1 (en) | 2006-12-20 | 2008-07-09 | sanofi-aventis | Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| ZA200904686B (en) | 2007-01-18 | 2010-09-29 | Sepracor Inc | Inhibitiors of D-amino acid oxidase |
| MX2009012685A (es) | 2007-05-31 | 2009-12-14 | Sepracor Inc | Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina. |
| WO2009151498A2 (en) * | 2008-03-28 | 2009-12-17 | Forest Laboratories Holdings Limited | Memantine formulations |
| US20100120740A1 (en) * | 2008-08-07 | 2010-05-13 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| CN102348683A (zh) * | 2009-03-10 | 2012-02-08 | 参天制药株式会社 | 含有4,6-二氯-1h-吲哚-2-羧酸衍生物或其盐作为有效成分的视神经损伤的预防或治疗剂 |
| US20110034434A1 (en) * | 2009-08-07 | 2011-02-10 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| CA2946153C (en) | 2014-04-30 | 2022-06-14 | Yufeng Jane Tseng | Use of known compounds as d-amino acid oxidase inhibitors |
| EP3512840B1 (en) | 2016-09-14 | 2024-03-06 | Yufeng Jane Tseng | Novel substituted benzimidazole derivatives as d-amino acid oxidase (daao) inhibitors |
| RU2020100230A (ru) | 2017-06-12 | 2021-07-13 | Глитек Ллс. | Лечение депрессии антагонистами nmda и антагонистами d2/5-ht2a или селективными антагонистами 5-нт2a |
| CN112707874A (zh) * | 2020-12-29 | 2021-04-27 | 广东中科药物研究有限公司 | 一种抗病毒化合物及其制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3010971A (en) * | 1960-08-04 | 1961-11-28 | Smith Kline French Lab | Cyclopropylamine derivatives and processes for their preparation |
| DK500285A (da) * | 1984-11-02 | 1986-05-03 | Glaxo Group Ltd | Cephalosporinantibiotika |
| US4960786A (en) * | 1989-04-24 | 1990-10-02 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| JPH0347123A (ja) * | 1989-05-05 | 1991-02-28 | G D Searle & Co | インドール―２―カルボキシレート化合物類を含有するｃｎｓ疾患治療用組成物 |
| EP0539503B1 (en) * | 1990-07-16 | 1996-04-03 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| US5284862A (en) * | 1991-03-18 | 1994-02-08 | Warner-Lambert Company | Derivatives of 2-carboxyindoles having pharmaceutical activity |
| US5145845A (en) * | 1991-05-14 | 1992-09-08 | Warner-Lambert Co. | Substituted 2-carboxylindoles having pharmaceutical activity |
-
1992
- 1992-04-16 GB GB929208492A patent/GB9208492D0/en active Pending
-
1993
- 1993-04-14 ZA ZA932642A patent/ZA932642B/xx unknown
- 1993-04-15 CA CA002094073A patent/CA2094073A1/en not_active Abandoned
- 1993-04-15 PL PL93305554A patent/PL176451B1/pl unknown
- 1993-04-15 IT IT93RM000236A patent/IT1265325B1/it active IP Right Grant
- 1993-04-15 WO PCT/EP1993/000938 patent/WO1993021153A1/en active IP Right Grant
- 1993-04-15 JP JP5517997A patent/JPH07505407A/ja active Pending
- 1993-04-15 GB GB9307808A patent/GB2266091B/en not_active Expired - Fee Related
- 1993-04-15 US US08/047,429 patent/US5374648A/en not_active Expired - Fee Related
- 1993-04-15 MX MX9302195A patent/MX9302195A/es not_active IP Right Cessation
- 1993-04-15 US US08/046,947 patent/US5373018A/en not_active Expired - Fee Related
- 1993-04-15 IS IS3994A patent/IS3994A/is unknown
- 1993-04-15 RO RO94-01658A patent/RO113242B1/ro unknown
- 1993-04-15 NZ NZ247413A patent/NZ247413A/en unknown
- 1993-04-15 CH CH1133/93A patent/CH685630A5/fr not_active IP Right Cessation
- 1993-04-15 SE SE9301241A patent/SE504336C2/sv not_active IP Right Cessation
- 1993-04-15 CA CA002094076A patent/CA2094076A1/en not_active Abandoned
- 1993-04-15 AT AT0075293A patent/AT403917B/de not_active IP Right Cessation
- 1993-04-15 EP EP93201103A patent/EP0568136A1/en not_active Withdrawn
- 1993-04-15 DK DK043193A patent/DK169890B1/da active
- 1993-04-15 CA CA002094075A patent/CA2094075A1/en not_active Abandoned
- 1993-04-15 HU HU9402975A patent/HU217964B/hu not_active IP Right Cessation
- 1993-04-15 LU LU88248A patent/LU88248A1/fr unknown
- 1993-04-15 KR KR1019940703668A patent/KR100264114B1/ko not_active IP Right Cessation
- 1993-04-15 CN CN93105797A patent/CN1042331C/zh not_active Expired - Fee Related
- 1993-04-15 MY MYPI93000690A patent/MY112232A/en unknown
- 1993-04-15 US US08/047,430 patent/US5374649A/en not_active Expired - Fee Related
- 1993-04-15 SK SK1241-94A patent/SK281941B6/sk unknown
- 1993-04-15 BE BE9300371A patent/BE1006343A5/fr active
- 1993-04-15 JP JP5088844A patent/JPH0649027A/ja active Pending
- 1993-04-15 CZ CZ942543A patent/CZ285799B6/cs not_active IP Right Cessation
- 1993-04-15 RU RU94045915A patent/RU2129544C1/ru active
- 1993-04-15 IL IL105412A patent/IL105412A/en not_active IP Right Cessation
- 1993-04-15 AU AU36923/93A patent/AU666927B2/en not_active Ceased
- 1993-04-15 ES ES09300771A patent/ES2105924B1/es not_active Expired - Lifetime
- 1993-04-15 GR GR930100154A patent/GR1001619B/el not_active IP Right Cessation
- 1993-04-15 FR FR9304452A patent/FR2690919B1/fr not_active Expired - Fee Related
- 1993-04-16 GE GEAP19932602A patent/GEP19991704B/en unknown
- 1993-04-16 AP APAP/P/1993/000524A patent/AP480A/en active
- 1993-05-06 TW TW082103531A patent/TW224457B/zh active
-
1994
- 1994-10-10 OA OA60570A patent/OA10103A/en unknown
- 1994-10-12 FI FI944800A patent/FI106198B/sv active
- 1994-10-14 NO NO943913A patent/NO301879B1/no not_active IP Right Cessation
- 1994-10-14 BG BG99111A patent/BG62136B1/bg unknown
- 1994-12-08 US US08/351,762 patent/US5510367A/en not_active Expired - Fee Related
-
1995
- 1995-06-29 HU HU95P/P00538P patent/HU211826A9/hu unknown
-
1997
- 1997-04-22 BR BR1100323-5A patent/BR1100323A/pt active IP Right Grant
- 1997-06-26 HK HK95797A patent/HK95797A/xx not_active IP Right Cessation
-
1998
- 1998-04-30 CY CY9802038A patent/CY2038B1/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BE1006343A5 (fr) | Derives de l'indole. | |
| EP0302788B1 (fr) | Dérivés de [(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 9H-pyrido[3,4-b]indole, leur préparation et leur application en thérapeutique | |
| EP0307303B1 (fr) | [(Pyrimidinyl-2)-aminoalkyl]-1 pipéridines, leur préparation et leur application en thérapeutique | |
| CZ398191A3 (en) | Novel 4-amino alkyl-2(3h)-indolones and pharmaceutical compositions containing them | |
| EP1567150B1 (fr) | Derives d indole-3-carboxamide, leur preparation et leur application en therapeutique | |
| FR2549058A1 (fr) | Nouveaux derives de la 1,4-dihydropyridine, leur preparation et leur utilisation comme medicaments | |
| WO2001044228A2 (fr) | Derives de quinazolinedione et phtalimide, leurs preparations et leurs applications en therapeutique | |
| FR2610932A1 (fr) | Nouvel acide piperazinecarboxylique, sa preparation et son utilisation comme medicament | |
| DE60027461T2 (de) | Megluminsalz einer spezifischen Chinolinsäure-Verbindung mit NMDA Rezeptor-Aktivität | |
| US4616011A (en) | Novel indole derivatives and pharmaceutical compositions containing same | |
| EP0402232A1 (fr) | Dérivés de pyridobenzoindole, leur préparation et les compositions qui les contiennent | |
| CH674008A5 (sv) | ||
| EP0266246A1 (fr) | Dérivés d'imidazo[4,5-b]pyridinone-2, leur préparation et leur application en thérapeutique | |
| EP1511728B1 (fr) | Derives d oxophenyl-cyclohexyl-propanolamine, leur preparati on et leur application en therapeutique | |
| WO2000063170A1 (fr) | Derives de cyclobutene-3,4-dione en tant qu'inhibiteurs de la phosphodiesterase 5 | |
| WO1995029154A1 (fr) | Nouveaux derives de benzylamines, leur procede de fabrication et les compositions pharmaceutiques les renfermant | |
| FR2690917A1 (fr) | Aminoesters, leur procédé de préparation et leur application en thérapeutique. | |
| EP0663903B1 (fr) | Derives de dihydro-1,2 oxo-2 amino-3 quinoxalines, leur preparation et leur application en therapeutique | |
| WO1998003485A1 (fr) | PHENOXYPROPANOLAMINES A ACTION ANTAGONISTE β3-ADRENERGIQUE | |
| WO1998015551A1 (fr) | Derives de quinuclidine en tant qu'antagonistes des recepteurs muscariniques | |
| FR2607134A1 (fr) | Nouveaux derives de l'octahydrobenzo(g)quinoleine, leur preparation et leur utilisation comme medicaments | |
| WO2000061554A1 (fr) | Derives de 1-amino ethylindole pour le traitement de l'incontinence urinaire | |
| WO2003011856A1 (fr) | Derives d'aminoalkylimidazole, leur preparation et leur utilisation en therapeutique | |
| BE898221A (fr) | Dérivés d'azepino (1,2-a) pyrimidine bronchodilatateurs, leurs sels d'addition d'acides et compositions pharmaceutiques qui les contiennent. | |
| JPH0233029B2 (ja) | Pirorijinjudotai |