CA2255727A1 - Produit pharmaceutique pour le traitement de troubles neurologiques et neuropsychiatriques - Google Patents
Produit pharmaceutique pour le traitement de troubles neurologiques et neuropsychiatriques Download PDFInfo
- Publication number
- CA2255727A1 CA2255727A1 CA002255727A CA2255727A CA2255727A1 CA 2255727 A1 CA2255727 A1 CA 2255727A1 CA 002255727 A CA002255727 A CA 002255727A CA 2255727 A CA2255727 A CA 2255727A CA 2255727 A1 CA2255727 A1 CA 2255727A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- ring
- substituted
- alkyl
- nitrogen
- 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.)
- Abandoned
Links
- 230000000926 neurological effect Effects 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 78
- 229910052799 carbon Chemical group 0.000 claims description 58
- 229910052757 nitrogen Inorganic materials 0.000 claims description 56
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 55
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 48
- -1 nitro, hydroxy Chemical group 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 230000002194 synthesizing effect Effects 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 239000001301 oxygen Substances 0.000 claims description 35
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 31
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 30
- 239000011593 sulfur Chemical group 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000006413 ring segment Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 206010015037 epilepsy Diseases 0.000 claims description 13
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 13
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 12
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 12
- 230000030833 cell death Effects 0.000 claims description 12
- 230000002708 enhancing effect Effects 0.000 claims description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 208000018198 spasticity Diseases 0.000 claims description 12
- 125000001118 alkylidene group Chemical group 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 210000003061 neural cell Anatomy 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 238000006467 substitution reaction Methods 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 206010019196 Head injury Diseases 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 208000007101 Muscle Cramp Diseases 0.000 claims description 6
- 208000005392 Spasm Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 241000534944 Thia Species 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 5
- 230000000269 nucleophilic effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 208000020358 Learning disease Diseases 0.000 claims description 4
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 201000003723 learning disability Diseases 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 3
- 208000014094 Dystonic disease Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 150000001721 carbon Chemical class 0.000 claims description 3
- 208000010118 dystonia Diseases 0.000 claims description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 125000002524 organometallic group Chemical group 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 125000005604 azodicarboxylate group Chemical group 0.000 claims description 2
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000005265 dialkylamine group Chemical group 0.000 claims description 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 2
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 2
- 125000002720 diazolyl group Chemical group 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims 3
- 208000019022 Mood disease Diseases 0.000 claims 2
- DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical compound N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 claims 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims 1
- 201000004810 Vascular dementia Diseases 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000005956 isoquinolyl group Chemical group 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 79
- 238000006243 chemical reaction Methods 0.000 description 47
- 239000004471 Glycine Substances 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 40
- 230000000694 effects Effects 0.000 description 22
- 239000000243 solution Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 18
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 102100023145 Sodium- and chloride-dependent glycine transporter 1 Human genes 0.000 description 13
- 101710083167 Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 13
- 230000027455 binding Effects 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 102100028886 Sodium- and chloride-dependent glycine transporter 2 Human genes 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002773 nucleotide Substances 0.000 description 9
- 125000003729 nucleotide group Chemical group 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 102000011714 Glycine Receptors Human genes 0.000 description 8
- 108010076533 Glycine Receptors Proteins 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- 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 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 101000631936 Rattus norvegicus Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000008351 acetate buffer Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000003185 calcium uptake Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- DBXIKTQNOQRNGL-UHFFFAOYSA-N ethyl 2-(3-benzhydryl-3,6-dihydro-2h-pyridin-1-yl)acetate Chemical compound C1N(CC(=O)OCC)CC=CC1C(C=1C=CC=CC=1)C1=CC=CC=C1 DBXIKTQNOQRNGL-UHFFFAOYSA-N 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 230000016273 neuron death Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000000946 synaptic effect Effects 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- HHZQLQREDATOBM-CODXZCKSSA-M Hydrocortisone Sodium Succinate Chemical compound [Na+].O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC([O-])=O)[C@@H]4[C@@H]3CCC2=C1 HHZQLQREDATOBM-CODXZCKSSA-M 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 4
- 210000000225 synapse Anatomy 0.000 description 4
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 3
- BGKFPRIGXAVYNX-UHFFFAOYSA-N 5,7-dichloro-4-oxo-1H-quinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=CC2=NC(C(=O)O)=CC(O)=C21 BGKFPRIGXAVYNX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- KWFUNBHQYSJTNZ-UHFFFAOYSA-N C(C)OC(C(N1CCCCC1)OC)=O Chemical compound C(C)OC(C(N1CCCCC1)OC)=O KWFUNBHQYSJTNZ-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 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 3
- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 3
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 229960003677 chloroquine Drugs 0.000 description 3
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 3
- 230000019771 cognition Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 210000000063 presynaptic terminal Anatomy 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 description 2
- 241001516584 Andrya Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000518994 Conta Species 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 101000631937 Homo sapiens Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241000282320 Panthera leo Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241001279009 Strychnos toxifera Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical group [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000003467 diminishing effect Effects 0.000 description 2
- ZKPLNIPNNCBHQC-UHFFFAOYSA-M ethyl 2-(3-benzhydrylpyridin-1-ium-1-yl)acetate;bromide Chemical compound [Br-].CCOC(=O)C[N+]1=CC=CC(C(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 ZKPLNIPNNCBHQC-UHFFFAOYSA-M 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 150000002332 glycine derivatives Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 210000004129 prosencephalon Anatomy 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960005453 strychnine Drugs 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JWXPYNYNEUYKOW-JTQLQIEISA-N (2s)-n-(4-nitrophenyl)pyrrolidine-2-carboxamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC(=O)[C@H]1NCCC1 JWXPYNYNEUYKOW-JTQLQIEISA-N 0.000 description 1
- JDZOTSLZMQDFLG-BTJKTKAUSA-N (z)-but-2-enedioic acid;2-(2,2-dicyclohexylethyl)piperidine Chemical compound OC(=O)\C=C/C(O)=O.C1CCCNC1CC(C1CCCCC1)C1CCCCC1 JDZOTSLZMQDFLG-BTJKTKAUSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 1
- MIRKCSZMSBCHIB-UHFFFAOYSA-N 2-ethyl-3,3-diphenylpyrrolidine Chemical compound CCC1NCCC1(C=1C=CC=CC=1)C1=CC=CC=C1 MIRKCSZMSBCHIB-UHFFFAOYSA-N 0.000 description 1
- VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 1
- WFJJMXWXQANJDG-UHFFFAOYSA-N 3-[bis(4-fluorophenyl)methoxy]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)OC1CNCCC1 WFJJMXWXQANJDG-UHFFFAOYSA-N 0.000 description 1
- HGVLJGHVYCBNBB-UHFFFAOYSA-N 3-benzhydrylpyridine Chemical compound C1=CC=CC=C1C(C=1C=NC=CC=1)C1=CC=CC=C1 HGVLJGHVYCBNBB-UHFFFAOYSA-N 0.000 description 1
- BTVVEKSXUOEVAY-UHFFFAOYSA-N 4,4-diphenylpiperidine Chemical compound C1CNCCC1(C=1C=CC=CC=1)C1=CC=CC=C1 BTVVEKSXUOEVAY-UHFFFAOYSA-N 0.000 description 1
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
- QKICWELGRMTQCR-UHFFFAOYSA-N 4-[(7-chloroquinolin-4-yl)azaniumyl]pentyl-diethylazanium;dihydrogen phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 QKICWELGRMTQCR-UHFFFAOYSA-N 0.000 description 1
- RIYGJSDIJWHXJS-UHFFFAOYSA-N 4-[4-(9-hydroxynonoxy)phenyl]benzonitrile Chemical compound C1=CC(OCCCCCCCCCO)=CC=C1C1=CC=C(C#N)C=C1 RIYGJSDIJWHXJS-UHFFFAOYSA-N 0.000 description 1
- ZWLWOTHDIGRTNE-UHFFFAOYSA-N 4-benzhydrylpyridine Chemical compound C1=CC=CC=C1C(C=1C=CN=CC=1)C1=CC=CC=C1 ZWLWOTHDIGRTNE-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- ZSZDLICNXAEVQW-UHFFFAOYSA-N 5-ethyl-4,4-diphenyl-2,3-dihydropyrrole Chemical compound CCC1=NCCC1(C=1C=CC=CC=1)C1=CC=CC=C1 ZSZDLICNXAEVQW-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
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000011045 Chloride Channels Human genes 0.000 description 1
- 108010062745 Chloride Channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000684936 Homo sapiens Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 101150046735 LEPR gene Proteins 0.000 description 1
- 101150063827 LEPROT gene Proteins 0.000 description 1
- LBOJYSIDWZQNJS-JKSUJKDBSA-N LSM-5387 Chemical compound C12=CC=CC=C2[C@@]2(C)C3=CC=CC=C3C[C@@H]1N2 LBOJYSIDWZQNJS-JKSUJKDBSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 206010061285 Mental disorder due to a general medical condition Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 108010049175 N-substituted Glycines Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 240000006474 Theobroma bicolor Species 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- QOKMIHKIMQNRES-UHFFFAOYSA-L [Cl-].[Cl-].[Cr++]Cc1ccccc1 Chemical compound [Cl-].[Cl-].[Cr++]Cc1ccccc1 QOKMIHKIMQNRES-UHFFFAOYSA-L 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives 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
- 150000001408 amides Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 125000003943 azolyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- VDXXMBLYDRQANY-UHFFFAOYSA-N ethyl 2-(3-benzhydrylpiperidin-1-yl)acetate Chemical compound C1N(CC(=O)OCC)CCCC1C(C=1C=CC=CC=1)C1=CC=CC=C1 VDXXMBLYDRQANY-UHFFFAOYSA-N 0.000 description 1
- VGXDMYGCHTXKEP-UHFFFAOYSA-N ethyl 2-[2-(2,2-dicyclohexylethyl)piperidin-1-yl]acetate Chemical compound CCOC(=O)CN1CCCCC1CC(C1CCCCC1)C1CCCCC1 VGXDMYGCHTXKEP-UHFFFAOYSA-N 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 230000000575 glycinergic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- LBOJYSIDWZQNJS-UHFFFAOYSA-N neurogard Chemical compound C12=CC=CC=C2C2(C)C3=CC=CC=C3CC1N2 LBOJYSIDWZQNJS-UHFFFAOYSA-N 0.000 description 1
- 230000008062 neuronal firing Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960004803 perhexiline maleate Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Virology (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Hospice & Palliative Care (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Abstract
Cette invention concerne un produit pharmaceutique destiné au traitement de troubles neurologiques ou neuropsychiatriques. Ledit produit pharmaceutique comprend un composé ayant les formules (I) et (II) ou un sel pharmaceutiquement acceptable dudit composé.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65584796A | 1996-05-31 | 1996-05-31 | |
| US80768197A | 1997-02-27 | 1997-02-27 | |
| US08/655,847 | 1997-02-27 | ||
| US08/807,681 | 1997-02-27 | ||
| PCT/US1997/009346 WO1997045423A1 (fr) | 1996-05-31 | 1997-05-29 | Produit pharmaceutique pour le traitement de troubles neurologiques et neuropsychiatriques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2255727A1 true CA2255727A1 (fr) | 1997-12-04 |
Family
ID=27097055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002255727A Abandoned CA2255727A1 (fr) | 1996-05-31 | 1997-05-29 | Produit pharmaceutique pour le traitement de troubles neurologiques et neuropsychiatriques |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0918767A4 (fr) |
| JP (2) | JP4403212B2 (fr) |
| AU (1) | AU737095B2 (fr) |
| CA (1) | CA2255727A1 (fr) |
| WO (1) | WO1997045423A1 (fr) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU737095B2 (en) * | 1996-05-31 | 2001-08-09 | Nps Pharmaceuticals, Inc. | Pharmaceutical for treating of neurological and neuropsychiatric disorders |
| EP1058684A1 (fr) * | 1998-03-06 | 2000-12-13 | Janssen Pharmaceutica N.V. | Inhibiteurs du transport de la glycine |
| TW555757B (en) | 1998-07-31 | 2003-10-01 | Akzo Nobel Nv | Aminomethylcarboxylic acid derivatives |
| HN1999000149A (es) | 1998-09-09 | 2000-01-12 | Pfizer Prod Inc | Derivados de 4,4-biarilpiperidina |
| UA75051C2 (en) * | 1999-09-03 | 2006-03-15 | Syngenta Participations Ag | Tetrahydropiridines as pesticides, a composition, a method for the preparation thereof and a method of controlling pests |
| TWI243173B (en) | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
| US20020120149A1 (en) | 2000-09-08 | 2002-08-29 | Ali Syed M. | Substituted hydrazine derivatives |
| AU2001290786A1 (en) | 2000-09-14 | 2002-03-26 | Gliatech, Inc. | Nitrogen-containing compounds and their use as glycine transport inhibitors |
| AR032653A1 (es) | 2001-02-09 | 2003-11-19 | Telik Inc | Inhibidores heterociclicos del trasportador de glicina 2 composiciones farmaceuticas, uso y metodos. |
| WO2003010196A2 (fr) | 2001-07-24 | 2003-02-06 | Genset S.A. | Nouveaux variants et exons du transporteur glyt1 |
| AU2002332659A1 (en) * | 2001-08-21 | 2003-03-03 | Sepracor, Inc. | 2-substituted piperidines that are ligands for monoamine receptors and transporters |
| WO2005100301A1 (fr) * | 2004-03-31 | 2005-10-27 | Eli Lilly And Company | Derives de la 2-aryloxyethyl glycine et leur utilisation comme inhibiteurs du transport de la glycine |
| ATE435650T1 (de) * | 2005-01-18 | 2009-07-15 | Hoffmann La Roche | 2,5-disubstituierte phenylmethanonderivative als glycintransporter-1-inhibitoren (glyt-1) zur behandlung von neurologischen und neuropsychiatrischen störungen |
| ES2452822T3 (es) | 2006-06-28 | 2014-04-02 | Amgen Inc. | Inhibidores del transportador 1 de glicina |
| ES2486299T3 (es) | 2007-12-12 | 2014-08-18 | Amgen Inc. | Inhibidores del transportador de glicina 1 |
| BRPI0907990A2 (pt) * | 2008-03-05 | 2015-12-29 | Neurosearch As | composto, composição farmacêutica, e, uso do composto |
| CN110372571B (zh) * | 2018-04-12 | 2022-11-15 | 中国科学院大连化学物理研究所 | 一种2-(2,2-二芳基乙基)-环胺衍生物或盐及合成和应用与组合物 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0686463B2 (ja) * | 1988-07-01 | 1994-11-02 | 明治製菓株式会社 | 新規セフェム化合物、その製造法及び抗菌剤 |
| CA2015949A1 (fr) * | 1989-05-22 | 1990-11-22 | Yasuo Ito | Derive de piperidine, methode de preparation et compose pharmaceutique le contenant |
| JPH03264562A (ja) * | 1989-05-22 | 1991-11-25 | Hokuriku Seiyaku Co Ltd | ピペリジン誘導体 |
| JPH03204885A (ja) * | 1989-12-28 | 1991-09-06 | Meiji Seika Kaisha Ltd | 新規セファロスポリン系化合物 |
| US5057524A (en) * | 1990-02-08 | 1991-10-15 | A. H. Robins Company Incorporated | 4-[diaryl)hydroxymethyl]-1-piperidinealkylcarboxylic acids, salts and esters useful in the treatment of allergic disorders |
| US5063235A (en) * | 1990-04-30 | 1991-11-05 | A. H. Robins Company, Inc. | 4-[(diaryl)hydromethyl]-1-piperidinealkanols and esters and carbamates thereof useful in the treatment of allergic disorders |
| JPH0517443A (ja) * | 1991-07-11 | 1993-01-26 | Hokuriku Seiyaku Co Ltd | ピペリジン誘導体 |
| AU737095B2 (en) * | 1996-05-31 | 2001-08-09 | Nps Pharmaceuticals, Inc. | Pharmaceutical for treating of neurological and neuropsychiatric disorders |
-
1997
- 1997-05-29 AU AU31510/97A patent/AU737095B2/en not_active Ceased
- 1997-05-29 CA CA002255727A patent/CA2255727A1/fr not_active Abandoned
- 1997-05-29 EP EP97926837A patent/EP0918767A4/fr not_active Withdrawn
- 1997-05-29 WO PCT/US1997/009346 patent/WO1997045423A1/fr not_active Ceased
- 1997-05-29 JP JP54300197A patent/JP4403212B2/ja not_active Expired - Fee Related
-
2009
- 2009-02-04 JP JP2009023296A patent/JP2009149663A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP4403212B2 (ja) | 2010-01-27 |
| JP2009149663A (ja) | 2009-07-09 |
| EP0918767A1 (fr) | 1999-06-02 |
| AU3151097A (en) | 1998-01-05 |
| WO1997045423A1 (fr) | 1997-12-04 |
| EP0918767A4 (fr) | 2000-04-26 |
| JP2001500107A (ja) | 2001-01-09 |
| AU737095B2 (en) | 2001-08-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU730789B2 (en) | Pharmaceutical for treatment of neurological and neuropsychiatric disorders | |
| US6191165B1 (en) | Pharmaceutical for treatment of neurological and neuropsychiatric disorders | |
| JP2009149663A (ja) | 神経障害および神経心理学的障害の治療のための製剤学的薬剤 | |
| JPH0757748B2 (ja) | 3−アミノピペリジン誘導体及び関連する窒素含有複素環化合物 | |
| HUT65831A (en) | Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutically acceptable salts | |
| JP2005519048A (ja) | GlyT1トランスポーター阻害剤ならびに神経病学および神経精神病学的障害の治療におけるその使用 | |
| US6001854A (en) | Pharmaceutical for treating of neurological and neuropsychiatric disorders | |
| RO119545B1 (ro) | Derivaţi de 4-aminotetrahidrobenzizoxazol ca inhibitori ai absorbţiei gaba | |
| JP2003502415A (ja) | 神経疾患に対するクロマン誘導体 | |
| IL93814A (en) | History of benzothiophyranilamines, their preparation and pharmaceutical preparations containing them | |
| HU211322A9 (en) | (2-thienyl)alkylamine derivaties having neuroprotective properties | |
| RU2465273C2 (ru) | ГЕТЕРОЦИКЛИЧЕСКИЕ НИЗКОМОЛЕКУЛЯРНЫЕ sAPP-МИМЕТИКИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБЫ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ | |
| EP1708704A2 (fr) | 4-aryle piperidines | |
| EP1140891A1 (fr) | Composes de 1,4-diazacyclo-heptane, procedeede preparation et applications medicamenteuses | |
| KR20010033998A (ko) | 신경학적 질병 치료용 1,4-디아자시클로헵탄 유도체 | |
| JP2003502421A (ja) | 化合物 | |
| MXPA00006078A (en) | 1,4-diazacycloheptane derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |