JP5393654B2 - 改善された心血管副作用プロフィールを呈する、ドーパミン受容体安定剤／調節剤のｎ−オキシド誘導体及び／又はジ−ｎ−オキシド誘導体 - Google Patents
改善された心血管副作用プロフィールを呈する、ドーパミン受容体安定剤／調節剤のｎ−オキシド誘導体及び／又はジ−ｎ−オキシド誘導体 Download PDFInfo
- Publication number
- JP5393654B2 JP5393654B2 JP2010502976A JP2010502976A JP5393654B2 JP 5393654 B2 JP5393654 B2 JP 5393654B2 JP 2010502976 A JP2010502976 A JP 2010502976A JP 2010502976 A JP2010502976 A JP 2010502976A JP 5393654 B2 JP5393654 B2 JP 5393654B2
- Authority
- JP
- Japan
- Prior art keywords
- disorders
- oxide
- compound
- treatment
- iatrogenic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001204 N-oxides Chemical class 0.000 title description 26
- 230000000694 effects Effects 0.000 title description 15
- 108050004812 Dopamine receptor Proteins 0.000 title description 13
- 102000015554 Dopamine receptor Human genes 0.000 title description 13
- 239000003381 stabilizer Substances 0.000 title description 5
- 230000002526 effect on cardiovascular system Effects 0.000 title description 2
- 230000001747 exhibiting effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 45
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 45
- 239000003814 drug Substances 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 208000035475 disorder Diseases 0.000 claims description 29
- 229960003638 dopamine Drugs 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 15
- 201000000980 schizophrenia Diseases 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 208000028017 Psychotic disease Diseases 0.000 claims description 12
- 208000012661 Dyskinesia Diseases 0.000 claims description 8
- 208000019022 Mood disease Diseases 0.000 claims description 7
- 208000016285 Movement disease Diseases 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 208000012239 Developmental disease Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 206010044565 Tremor Diseases 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 230000006870 function Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000019116 sleep disease Diseases 0.000 claims description 5
- 208000004547 Hallucinations Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 206010034010 Parkinsonism Diseases 0.000 claims description 4
- 230000003920 cognitive function Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- HSRUNQNYTPVPRR-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-oxido-1-propylpiperidin-1-ium Chemical compound C1C[N+](CCC)([O-])CCC1C1=CC=CC(S(C)(=O)=O)=C1 HSRUNQNYTPVPRR-UHFFFAOYSA-N 0.000 claims description 3
- 208000014094 Dystonic disease Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 3
- 208000003028 Stuttering Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 208000010118 dystonia Diseases 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 230000033001 locomotion Effects 0.000 claims description 3
- 230000002503 metabolic effect Effects 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000020706 Autistic disease Diseases 0.000 claims description 2
- 208000029028 brain injury Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 230000007659 motor function Effects 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 2
- 208000015891 sexual disease Diseases 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- 230000000642 iatrogenic effect Effects 0.000 claims 6
- 206010003805 Autism Diseases 0.000 claims 1
- 206010006100 Bradykinesia Diseases 0.000 claims 1
- 206010050012 Bradyphrenia Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 208000006083 Hypokinesia Diseases 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 230000001146 hypoxic effect Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000002458 infectious effect Effects 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 230000030363 nerve development Effects 0.000 claims 1
- 231100000331 toxic Toxicity 0.000 claims 1
- 230000002588 toxic effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- 229940079593 drug Drugs 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 31
- 239000002904 solvent Substances 0.000 description 27
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- -1 tertiary amine N-oxides Chemical class 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 150000003512 tertiary amines Chemical class 0.000 description 9
- SSNWMPRWIIBOCB-UHFFFAOYSA-N 4-(3-methylsulfanylphenyl)-1-propylpiperidin-4-ol Chemical compound C1CN(CCC)CCC1(O)C1=CC=CC(SC)=C1 SSNWMPRWIIBOCB-UHFFFAOYSA-N 0.000 description 8
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 230000001624 sedative effect Effects 0.000 description 7
- AUEVPUKHNGEVFZ-UHFFFAOYSA-N 4-(3-methylsulfanylphenyl)-1-propyl-3,6-dihydro-2h-pyridine Chemical compound C1N(CCC)CCC(C=2C=C(SC)C=CC=2)=C1 AUEVPUKHNGEVFZ-UHFFFAOYSA-N 0.000 description 6
- KARJWCLKKGSFBV-UHFFFAOYSA-N 4-(3-methylsulfanylphenyl)-1-propylpiperidine Chemical compound C1CN(CCC)CCC1C1=CC=CC(SC)=C1 KARJWCLKKGSFBV-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- XADUXZWGQXGKNK-UHFFFAOYSA-N 1-benzyl-3-(3-methoxyphenyl)piperidine Chemical compound COC1=CC=CC(C2CN(CC=3C=CC=CC=3)CCC2)=C1 XADUXZWGQXGKNK-UHFFFAOYSA-N 0.000 description 5
- RVWZUOPFHTYIEO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Natural products C1=C(O)C=C2C(C(=O)O)=CNC2=C1 RVWZUOPFHTYIEO-UHFFFAOYSA-N 0.000 description 5
- 239000003310 5-hydroxyindoleacetic acid Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- AMAPEXTUMXQULJ-APQDOHRLSA-N Morphine N-oxide Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)(=O)[C@@H]3CC5=CC=C4O AMAPEXTUMXQULJ-APQDOHRLSA-N 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 150000002978 peroxides Chemical class 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- NKYFJZAKUPSUSH-UHFFFAOYSA-N 1-bromo-3-methylsulfanylbenzene Chemical compound CSC1=CC=CC(Br)=C1 NKYFJZAKUPSUSH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010012239 Delusion Diseases 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- 101150109352 acr-16 gene Proteins 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
- 231100000868 delusion Toxicity 0.000 description 4
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 4
- 230000003291 dopaminomimetic effect Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000001690 micro-dialysis Methods 0.000 description 4
- 229960005181 morphine Drugs 0.000 description 4
- 229960002715 nicotine Drugs 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- 230000002085 persistent effect Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000001839 systemic circulation Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 208000016686 tic disease Diseases 0.000 description 4
- JQIXPQADNAGPAW-UHFFFAOYSA-N 1-benzyl-3-(3-methoxyphenyl)-3,6-dihydro-2h-pyridine Chemical compound COC1=CC=CC(C2C=CCN(CC=3C=CC=CC=3)C2)=C1 JQIXPQADNAGPAW-UHFFFAOYSA-N 0.000 description 3
- PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 208000027534 Emotional disease Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000001089 Multiple system atrophy Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 230000001149 cognitive effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229960002690 fluphenazine Drugs 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000003340 mental effect Effects 0.000 description 3
- 239000003176 neuroleptic agent Substances 0.000 description 3
- 230000000701 neuroleptic effect Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- GZVBVBMMNFIXGE-CQSZACIVSA-N osu-6162 Chemical compound C1N(CCC)CCC[C@H]1C1=CC=CC(S(C)(=O)=O)=C1 GZVBVBMMNFIXGE-CQSZACIVSA-N 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 150000004885 piperazines Chemical class 0.000 description 3
- YGKUEOZJFIXDGI-UHFFFAOYSA-N pridopidine Chemical compound C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGKUEOZJFIXDGI-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000932 sedative agent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- GXMDLXQESSRSFB-ZWKGOLINSA-N (4r,4as,7ar,12bs)-4a-hydroxy-9-methoxy-3-methyl-3-oxido-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7-one Chemical compound C([C@@]1(O)[C@H]([N+](CC[C@@]112)(C)[O-])C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC GXMDLXQESSRSFB-ZWKGOLINSA-N 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 2
- YGDZKYYCJUNORF-UHFFFAOYSA-N 1-propylpiperidin-4-one Chemical compound CCCN1CCC(=O)CC1 YGDZKYYCJUNORF-UHFFFAOYSA-N 0.000 description 2
- HTSNFXAICLXZMA-UHFFFAOYSA-N 3-(1-propyl-3-piperidinyl)phenol Chemical compound C1N(CCC)CCCC1C1=CC=CC(O)=C1 HTSNFXAICLXZMA-UHFFFAOYSA-N 0.000 description 2
- LXCUAFVVTHZALS-UHFFFAOYSA-N 3-(3-methoxyphenyl)piperidine Chemical compound COC1=CC=CC(C2CNCCC2)=C1 LXCUAFVVTHZALS-UHFFFAOYSA-N 0.000 description 2
- SKJVHGNPOINIFA-UHFFFAOYSA-N 3-benzyl-1-(3-methoxyphenyl)cyclohexan-1-ol Chemical compound COC1=CC=CC(C2(O)CC(CC=3C=CC=CC=3)CCC2)=C1 SKJVHGNPOINIFA-UHFFFAOYSA-N 0.000 description 2
- MVDVFRYFFSLDGH-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-oxido-1-propyl-3,6-dihydro-2h-pyridin-1-ium Chemical compound C1[N+](CCC)([O-])CCC(C=2C=C(C=CC=2)S(C)(=O)=O)=C1 MVDVFRYFFSLDGH-UHFFFAOYSA-N 0.000 description 2
- URHYIWVFGYKNHG-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-oxido-1-propylpiperidin-1-ium-4-ol Chemical compound C1C[N+](CCC)([O-])CCC1(O)C1=CC=CC(S(C)(=O)=O)=C1 URHYIWVFGYKNHG-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000031091 Amnestic disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000027448 Attention Deficit and Disruptive Behavior disease Diseases 0.000 description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 2
- 206010008748 Chorea Diseases 0.000 description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 2
- 208000006561 Cluster Headache Diseases 0.000 description 2
- 240000007154 Coffea arabica Species 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 2
- 208000021584 Expressive language disease Diseases 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 208000009829 Lewy Body Disease Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 206010061296 Motor dysfunction Diseases 0.000 description 2
- 206010028343 Muscle tone abnormalities Diseases 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000012075 Paroxysmal dystonia Diseases 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 206010068100 Vascular parkinsonism Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000006986 amnesia Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229940045348 brown mixture Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
- 229960001076 chlorpromazine Drugs 0.000 description 2
- LFDFWIIFGRXCFR-UHFFFAOYSA-N chlorpromazine N-oxide Chemical compound C1=C(Cl)C=C2N(CCC[N+](C)([O-])C)C3=CC=CC=C3SC2=C1 LFDFWIIFGRXCFR-UHFFFAOYSA-N 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical class C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 208000018912 cluster headache syndrome Diseases 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
- 229960004126 codeine Drugs 0.000 description 2
- 235000016213 coffee Nutrition 0.000 description 2
- 235000013353 coffee beverage Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 208000012839 conversion disease Diseases 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- BCQMRZRAWHNSBF-UHFFFAOYSA-N desmethylprodine Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CCN(C)CC1 BCQMRZRAWHNSBF-UHFFFAOYSA-N 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical class II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 2
- 201000003631 narcolepsy Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 208000030212 nutrition disease Diseases 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- 150000004967 organic peroxy acids Chemical class 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229960002085 oxycodone Drugs 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 208000022821 personality disease Diseases 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 208000014321 polymorphic ventricular tachycardia Diseases 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000000698 schizophrenic effect Effects 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 201000009032 substance abuse Diseases 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- RWFBQHICRCUQJJ-JQWIXIFHSA-N trans-(S)-nicotine N(1')-oxide Chemical compound C[N@+]1([O-])CCC[C@H]1C1=CC=CN=C1 RWFBQHICRCUQJJ-JQWIXIFHSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 206010047302 ventricular tachycardia Diseases 0.000 description 2
- ZIZQARJISFQDMO-TUVFQOJMSA-N (1R,9R,10R)-4-methoxy-17-methyl-17-oxido-17-azoniatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene Chemical compound C1CCC[C@H]2[C@]3([H])[N+]([O-])(C)CC[C@@]21C1=CC(OC)=CC=C1C3 ZIZQARJISFQDMO-TUVFQOJMSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-L (2r,3r)-2,3-dibenzoyloxybutanedioate Chemical compound O([C@@H](C(=O)[O-])[C@@H](OC(=O)C=1C=CC=CC=1)C([O-])=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-L 0.000 description 1
- DXDIHODZARUBLA-IODNYQNNSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid;hydrate Chemical compound O.O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 DXDIHODZARUBLA-IODNYQNNSA-N 0.000 description 1
- FVVZCYAZJLEMGV-GPLBXWCQSA-N (4r,4ar,7ar,12bs)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O FVVZCYAZJLEMGV-GPLBXWCQSA-N 0.000 description 1
- OJOOUQMEQYGIDH-WEOKCGDASA-N (4r,4ar,7ar,12bs)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC OJOOUQMEQYGIDH-WEOKCGDASA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- DZKRDHLYQRTDBU-UPHRSURJSA-N (z)-but-2-enediperoxoic acid Chemical compound OOC(=O)\C=C/C(=O)OO DZKRDHLYQRTDBU-UPHRSURJSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- JCSCMMDQBWQISZ-UHFFFAOYSA-N 1-(1-propylcyclohexa-2,4-dien-1-yl)piperidine Chemical compound C1CCCCN1C1(CCC)CC=CC=C1 JCSCMMDQBWQISZ-UHFFFAOYSA-N 0.000 description 1
- DAHDPFPMRKVRHX-UHFFFAOYSA-N 1-benzyl-5-(3-methoxyphenyl)-3,6-dihydro-2h-pyridine Chemical compound COC1=CC=CC(C=2CN(CC=3C=CC=CC=3)CCC=2)=C1 DAHDPFPMRKVRHX-UHFFFAOYSA-N 0.000 description 1
- BBQQULRBTOMLTC-UHFFFAOYSA-N 1-benzylpiperidin-3-one Chemical compound C1C(=O)CCCN1CC1=CC=CC=C1 BBQQULRBTOMLTC-UHFFFAOYSA-N 0.000 description 1
- CSXPUTRJYNPOMI-UHFFFAOYSA-N 1-oxido-1-(1-propylcyclohexa-2,4-dien-1-yl)piperidin-1-ium Chemical compound C1CCCC[N+]1([O-])C1(CCC)CC=CC=C1 CSXPUTRJYNPOMI-UHFFFAOYSA-N 0.000 description 1
- SZWFGCRTUHNBQX-UHFFFAOYSA-N 1-propylpiperidin-3-one Chemical compound CCCN1CCCC(=O)C1 SZWFGCRTUHNBQX-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical class C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 1
- 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 1
- 108091005479 5-HT2 receptors Proteins 0.000 description 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 208000036640 Asperger disease Diseases 0.000 description 1
- 201000006062 Asperger syndrome Diseases 0.000 description 1
- 208000009017 Athetosis Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 102000007527 Autoreceptors Human genes 0.000 description 1
- 108010071131 Autoreceptors Proteins 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- QZPAXHYFJLXMGL-BBWFWOEESA-N CC1=CC=CC([C@]2(CC3)[C@H]4CCCC2)=C1C[C@H]4N3O Chemical compound CC1=CC=CC([C@]2(CC3)[C@H]4CCCC2)=C1C[C@H]4N3O QZPAXHYFJLXMGL-BBWFWOEESA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 208000010248 Cerebrovascular Trauma Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- OGUCZBIQSYYWEF-UHFFFAOYSA-N Clozapine N-oxide Chemical compound C1C[N+](C)([O-])CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 OGUCZBIQSYYWEF-UHFFFAOYSA-N 0.000 description 1
- 206010010305 Confusional state Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- 229940098778 Dopamine receptor agonist Drugs 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000001836 Firesetting Behavior Diseases 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 208000001613 Gambling Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 206010020852 Hypertonia Diseases 0.000 description 1
- 208000030990 Impulse-control disease Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 238000006219 Matteson homologation reaction Methods 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 206010027387 Merycism Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019896 Motor Skills disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010061533 Myotonia Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010052794 Panic disorder with agoraphobia Diseases 0.000 description 1
- 206010033668 Panic disorder without agoraphobia Diseases 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 208000036353 Rett disease Diseases 0.000 description 1
- 208000011390 Rumination Syndrome Diseases 0.000 description 1
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 208000019568 Shared Paranoid disease Diseases 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 208000028790 Speech Sound disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010042209 Stress Diseases 0.000 description 1
- 208000011962 Substance-induced mood disease Diseases 0.000 description 1
- 231100000395 Substance-induced mood disorder Toxicity 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 208000001407 Vascular Headaches Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000026345 acute stress disease Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- UPOYFZYFGWBUKL-UHFFFAOYSA-N amiphenazole Chemical compound S1C(N)=NC(N)=C1C1=CC=CC=C1 UPOYFZYFGWBUKL-UHFFFAOYSA-N 0.000 description 1
- 229950001798 amiphenazole Drugs 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940125709 anorectic agent Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001090 anti-dopaminergic effect Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 208000022257 bipolar II disease Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- LJVNYCDXBXGQIK-UHFFFAOYSA-N chembl440512 Chemical compound S1C(C)=CC2=C1NC1=CC=CC=C1N=C2N1CC[N+](C)([O-])CC1 LJVNYCDXBXGQIK-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000024825 childhood disintegrative disease Diseases 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 208000030251 communication disease Diseases 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 230000010249 dopaminergic function Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 206010020765 hypersomnia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 208000015046 intermittent explosive disease Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 229960004715 morphine sulfate Drugs 0.000 description 1
- GRVOTVYEFDAHCL-RTSZDRIGSA-N morphine sulfate pentahydrate Chemical compound O.O.O.O.O.OS(O)(=O)=O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O GRVOTVYEFDAHCL-RTSZDRIGSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- KIWSYRHAAPLJFJ-DNZSEPECSA-N n-[(e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enyl]pyridine-3-carboxamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/CNC(=O)C1=CC=CN=C1 KIWSYRHAAPLJFJ-DNZSEPECSA-N 0.000 description 1
- 239000003887 narcotic antagonist Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000037860 neuroleptic-induced Akathisia Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940051807 opiod analgesics morphinan derivative Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 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
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 208000015212 rumination disease Diseases 0.000 description 1
- 230000024053 secondary metabolic process Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 208000013623 stereotypic movement disease Diseases 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical class C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 1
- 229960002324 trifluoperazine Drugs 0.000 description 1
- 150000003682 vanadium compounds Chemical class 0.000 description 1
- 208000010926 vascular brain injury Diseases 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/94—Oxygen atom, e.g. piperidine N-oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (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)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Anesthesiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Psychology (AREA)
- AIDS & HIV (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0700893 | 2007-04-12 | ||
| SE0700893-1 | 2007-04-12 | ||
| PCT/SE2008/050414 WO2008127188A1 (en) | 2007-04-12 | 2008-04-11 | N-oxide and/or di-n-oxide derivatives of dopamine receptor stabilizers/modulators displaying improved cardiovascular side-effects profiles |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010523651A JP2010523651A (ja) | 2010-07-15 |
| JP2010523651A5 JP2010523651A5 (enExample) | 2011-05-26 |
| JP5393654B2 true JP5393654B2 (ja) | 2014-01-22 |
Family
ID=39864178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010502976A Expired - Fee Related JP5393654B2 (ja) | 2007-04-12 | 2008-04-11 | 改善された心血管副作用プロフィールを呈する、ドーパミン受容体安定剤／調節剤のｎ−オキシド誘導体及び／又はジ−ｎ−オキシド誘導体 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US9139525B2 (enExample) |
| EP (1) | EP2146961B1 (enExample) |
| JP (1) | JP5393654B2 (enExample) |
| CN (1) | CN101711236B (enExample) |
| AU (1) | AU2008239841B2 (enExample) |
| BR (1) | BRPI0810161A2 (enExample) |
| CA (1) | CA2683719C (enExample) |
| CY (1) | CY1115337T1 (enExample) |
| DK (1) | DK2146961T3 (enExample) |
| ES (1) | ES2458592T3 (enExample) |
| HR (1) | HRP20140380T1 (enExample) |
| IL (1) | IL201401A (enExample) |
| MX (1) | MX2009011020A (enExample) |
| NZ (1) | NZ580856A (enExample) |
| PL (1) | PL2146961T3 (enExample) |
| PT (1) | PT2146961E (enExample) |
| RU (1) | RU2470013C2 (enExample) |
| SI (1) | SI2146961T1 (enExample) |
| WO (1) | WO2008127188A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE46117E1 (en) | 1999-12-22 | 2016-08-23 | Teva Pharmaceuticals International Gmbh | Modulators of dopamine neurotransmission |
| EP2367788A1 (en) * | 2008-11-24 | 2011-09-28 | NSAB, Filial af NeuroSearch Sweden AB, Sverige | 3-phenyl-3-methoxypyrrolidine derivatives as modulators of cortical catecholaminergic neurotransmission |
| WO2011107583A1 (en) | 2010-03-04 | 2011-09-09 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Substituted 4-phenyl-n-alkyl-piperidines for preventing onset or slowing progression of neurodegenerative disorders |
| BR112013005125A2 (pt) | 2010-09-03 | 2016-08-16 | Ivax Int Gmbh | deuterados análogos dos pridopidine úteis como estabilizadores dopaminérgicos |
| US9018202B2 (en) * | 2010-12-03 | 2015-04-28 | Allergan, Inc. | Methods for treating diseases of the retina |
| CA2847736A1 (en) | 2011-09-07 | 2013-03-14 | IVAX International GmbH | A new polymorphic form of pridopidine hydrochloride |
| MX347209B (es) | 2011-12-08 | 2017-04-19 | Teva Pharmaceuticals Int Gmbh | La sal de bromhidrato de pridopidina. |
| US20130267552A1 (en) | 2012-04-04 | 2013-10-10 | IVAX International GmbH | Pharmaceutical compositions for combination therapy |
| US11090297B2 (en) | 2013-06-21 | 2021-08-17 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating huntington's disease |
| JP2016523862A (ja) | 2013-06-21 | 2016-08-12 | テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハーＴｅｖａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | ハンチントン病を治療するための高用量プリドピジンの使用 |
| TW201613859A (en) | 2014-06-30 | 2016-04-16 | Teva Pharma | Analogs of PRIDOPIDINE, their preparation and use |
| CA2970799A1 (en) | 2014-12-22 | 2016-06-30 | Teva Pharmaceuticals International Gmbh | L-tartrate salt of pridopidine |
| US11471449B2 (en) | 2015-02-25 | 2022-10-18 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine to improve cognitive function and for treating Alzheimer's disease |
| HUE060353T2 (hu) | 2015-02-25 | 2023-02-28 | Prilenia Neurotherapeutics Ltd | Pridopidin alkalmazása memória javítására |
| AR105434A1 (es) | 2015-07-22 | 2017-10-04 | Teva Pharmaceuticals Int Gmbh | Proceso para preparar pridopidina |
| JP7034488B2 (ja) | 2016-02-24 | 2022-03-14 | プリレニア・ニューロセラピューティクス・エルティーディー | プリドピジンを使用する神経変性眼疾患の治療 |
| CA3035099C (en) | 2016-08-24 | 2023-01-17 | Prilenia Therapeutics Development Ltd. | Use of pridopidine for treating dystonias |
| HUE071008T2 (hu) | 2016-08-24 | 2025-07-28 | Prilenia Neurotherapeutics Ltd | Pridopidin alkalmazása mûködési hanyatlás kezelésére |
| US12102627B2 (en) | 2016-09-16 | 2024-10-01 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine for treating rett syndrome |
| IL268125B2 (en) | 2017-01-20 | 2023-04-01 | Prilenia Neurotherapeutics Ltd | Pridopidine for the treatment of fragile x syndrome |
| HUE061505T2 (hu) | 2017-08-14 | 2023-07-28 | Prilenia Neurotherapeutics Ltd | Módszer amyothrophiás lateralsclerosis kezelésére pridopidinnel |
| EA202090542A1 (ru) | 2017-08-30 | 2020-06-08 | Приления Ньюротерапьютикс Лтд. | Высококонцентрированные лекарственные формы придопидина |
| AU2018329628B2 (en) | 2017-09-08 | 2021-04-22 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| US12036213B2 (en) | 2017-09-08 | 2024-07-16 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| CN113395964A (zh) | 2019-02-04 | 2021-09-14 | 普瑞尼亚神经治疗有限公司 | 用于帕金森氏病和与帕金森症相关的其它疾病的低剂量普利多匹定 |
| CN116472043A (zh) * | 2020-10-20 | 2023-07-21 | 普瑞尼亚神经治疗有限公司 | 普利多匹定和类似物用于治疗焦虑和抑郁的用途 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1217296A (en) | 1917-01-11 | 1917-02-27 | Lewis A Peckham | Shock-absorber. |
| US2813098A (en) | 1955-08-16 | 1957-11-12 | Upjohn Co | 3-methoxy-n-methylmorphinan n-oxide |
| US2813097A (en) | 1955-08-16 | 1957-11-12 | Upjohn Co | 3-hydroxy-n-methylmorphinan-n-oxide |
| US3131185A (en) | 1959-03-18 | 1964-04-28 | Orsymonde | Nicotinic esters of hydroxyl derivatives of the phenanthrenic alkaloids of opium, and process for the preparation of these esters |
| BE638369A (enExample) | 1962-10-10 | |||
| CH481123A (de) | 1966-09-21 | 1969-11-15 | Geigy Ag J R | Verfahren zur Herstellung von neuen, kondensierten heterocyclischen Verbindungen |
| CA2071897A1 (en) | 1989-12-28 | 1991-06-29 | Richard A. Glennon | Sigma receptor ligands and the use thereof |
| AU653837B2 (en) * | 1991-04-17 | 1994-10-13 | Pharmacia & Upjohn Company | Substituted phenylazacycloalkanes as CNS agents |
| PT100639A (pt) | 1991-06-27 | 1993-09-30 | Univ Virginia Commonwealth | Metodo para o tratamento terapeutico com compostos que sao ligandos ao receptor sigma e compostos ai utilizados, nomeadamente derivados fenilalquil-amina, aminotetralina,piperazina e piperidina |
| IL112099A (en) * | 1993-12-23 | 1999-07-14 | Ortho Pharma Corp | N-oxides of 4-arylpiperazines and 4-arylpiperidines and pharmaceutical compositions containing them |
| CA2144669A1 (en) | 1994-03-29 | 1995-09-30 | Kozo Akasaka | Biphenyl derivatives |
| DE69912635T2 (de) * | 1998-11-23 | 2004-05-13 | Sepracor Inc., Marlborough | Olanzapin-n-oxide enthaltende pharmaceutische zusammensetzungen |
| SE9904723D0 (sv) * | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
| SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
| SE0200301D0 (sv) | 2002-02-01 | 2002-02-01 | Axon Biochemicals Bv | Thio-carbostyril derivative |
| DE602005017784D1 (de) * | 2004-06-08 | 2009-12-31 | Nsab, Filial Af Neurosearch Sweden Ab | Neue disubstituierte phenylpiperidine als modulatoren der dopamin- und serotoninneurotransmission |
| ATE469885T1 (de) | 2004-06-08 | 2010-06-15 | Nsab Af Neurosearch Sweden Ab | Neue disubstituierte phenylpiperidine und piperazine als modulatoren der dopamin- neurotransmission |
| AU2005273961A1 (en) * | 2004-08-11 | 2006-02-23 | Williamsburg Holdings Llc | Noncardiotoxic pharmaceutical compounds |
| DK1802573T3 (en) * | 2004-10-13 | 2016-12-19 | Teva Pharmaceuticals Int Gmbh | METHOD OF SYNTHESIS OF 4- (3-METHANSULPHONYLPHENYL) -1-N-PROPYL-PIPERIDINE. |
| JP2009504799A (ja) | 2005-08-22 | 2009-02-05 | ソルベイ・フアーマシユーチカルズ・ベー・ブイ | ピペラジンおよびピペリジン誘導体のプロドラッグとしてのｎ−オキシド |
| SE529246C2 (sv) * | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
| CN101432279A (zh) * | 2006-05-02 | 2009-05-13 | 索尔瓦药物有限公司 | 吡啶基甲基哌嗪和吡啶基甲基哌啶衍生物的n-氧化物 |
| WO2011107583A1 (en) * | 2010-03-04 | 2011-09-09 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Substituted 4-phenyl-n-alkyl-piperidines for preventing onset or slowing progression of neurodegenerative disorders |
| US20130203886A1 (en) * | 2010-03-05 | 2013-08-08 | Nileshkumar Prakash Kukalyekar | Process for the production of an uhmwpe article |
| BR112013005125A2 (pt) * | 2010-09-03 | 2016-08-16 | Ivax Int Gmbh | deuterados análogos dos pridopidine úteis como estabilizadores dopaminérgicos |
| CA2847736A1 (en) | 2011-09-07 | 2013-03-14 | IVAX International GmbH | A new polymorphic form of pridopidine hydrochloride |
| MX347209B (es) * | 2011-12-08 | 2017-04-19 | Teva Pharmaceuticals Int Gmbh | La sal de bromhidrato de pridopidina. |
| US20130267552A1 (en) * | 2012-04-04 | 2013-10-10 | IVAX International GmbH | Pharmaceutical compositions for combination therapy |
| MX2015003812A (es) * | 2012-09-27 | 2015-07-17 | Teva Pharma | Combinacion de rasagilina y pridopidina para tratar trastornos neurodegenerativos, en particular enfermedad de huntington. |
| EA201590655A8 (ru) * | 2012-09-27 | 2016-07-29 | Тева Фармасьютикал Индастриз Лтд. | Комбинация лахинимода и придопидина для лечения нейродегенеративных нарушений |
-
2008
- 2008-04-11 DK DK08741904T patent/DK2146961T3/da active
- 2008-04-11 PL PL08741904T patent/PL2146961T3/pl unknown
- 2008-04-11 NZ NZ580856A patent/NZ580856A/en unknown
- 2008-04-11 WO PCT/SE2008/050414 patent/WO2008127188A1/en not_active Ceased
- 2008-04-11 SI SI200831188T patent/SI2146961T1/sl unknown
- 2008-04-11 JP JP2010502976A patent/JP5393654B2/ja not_active Expired - Fee Related
- 2008-04-11 CN CN2008800175988A patent/CN101711236B/zh not_active Expired - Fee Related
- 2008-04-11 CA CA2683719A patent/CA2683719C/en not_active Expired - Fee Related
- 2008-04-11 HR HRP20140380AT patent/HRP20140380T1/hr unknown
- 2008-04-11 EP EP20080741904 patent/EP2146961B1/en not_active Not-in-force
- 2008-04-11 MX MX2009011020A patent/MX2009011020A/es unknown
- 2008-04-11 PT PT08741904T patent/PT2146961E/pt unknown
- 2008-04-11 RU RU2009141300/04A patent/RU2470013C2/ru not_active IP Right Cessation
- 2008-04-11 AU AU2008239841A patent/AU2008239841B2/en not_active Ceased
- 2008-04-11 BR BRPI0810161 patent/BRPI0810161A2/pt not_active IP Right Cessation
- 2008-04-11 US US12/595,472 patent/US9139525B2/en active Active
- 2008-04-11 ES ES08741904T patent/ES2458592T3/es active Active
-
2009
- 2009-10-11 IL IL201401A patent/IL201401A/en not_active IP Right Cessation
-
2014
- 2014-04-25 CY CY20141100304T patent/CY1115337T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL201401A0 (en) | 2010-05-31 |
| NZ580856A (en) | 2011-11-25 |
| PT2146961E (pt) | 2014-04-30 |
| RU2470013C2 (ru) | 2012-12-20 |
| IL201401A (en) | 2015-10-29 |
| PL2146961T3 (pl) | 2014-09-30 |
| ES2458592T3 (es) | 2014-05-06 |
| WO2008127188A1 (en) | 2008-10-23 |
| US9139525B2 (en) | 2015-09-22 |
| SI2146961T1 (sl) | 2014-08-29 |
| AU2008239841B2 (en) | 2013-07-18 |
| EP2146961B1 (en) | 2014-01-29 |
| DK2146961T3 (da) | 2014-04-28 |
| BRPI0810161A2 (pt) | 2014-12-30 |
| EP2146961A4 (en) | 2011-08-03 |
| JP2010523651A (ja) | 2010-07-15 |
| CN101711236B (zh) | 2012-10-31 |
| CN101711236A (zh) | 2010-05-19 |
| RU2009141300A (ru) | 2011-05-20 |
| AU2008239841A1 (en) | 2008-10-23 |
| CA2683719C (en) | 2015-07-14 |
| EP2146961A1 (en) | 2010-01-27 |
| HRP20140380T1 (hr) | 2014-08-15 |
| US20100105736A1 (en) | 2010-04-29 |
| CA2683719A1 (en) | 2008-10-23 |
| CY1115337T1 (el) | 2017-01-04 |
| MX2009011020A (es) | 2009-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5393654B2 (ja) | 改善された心血管副作用プロフィールを呈する、ドーパミン受容体安定剤／調節剤のｎ−オキシド誘導体及び／又はジ−ｎ−オキシド誘導体 | |
| JP5524939B2 (ja) | 胃腸疾患および中枢神経系疾患の治療のための立体異性体化合物と方法 | |
| HUP0203872A2 (hu) | Helyettesített 4-(fenil-N-alkil)-piperazin és piperidinszármazékok, alkalmazásuk dopamin neurotranszmissziós modulátorként és ezeket tartalmazó gyógyszerkészítmények | |
| JP4937124B2 (ja) | ドーパミン神経伝達のモジュレーターとしての新規に提供されるフェニルピペリジン／ピペラジン | |
| AU708010B2 (en) | Novel heterocyclic compounds | |
| CZ302907B6 (cs) | Substituovaná (4-fenyl-N-alkyl)piperidinová sloucenina, její použití a farmaceutická kompozice s jejím obsahem | |
| AU2007251663B2 (en) | 4-[(3-fluorophenoxy)phenylmethyl]piperidine methanesulfonate: uses, process of synthesis and pharmaceutical compositions | |
| US20080085915A1 (en) | Compounds and methods for the treatment of gastrointestinal and central nervous system disorders | |
| EP4185578A1 (en) | Ibogaine analogs as therapeutics for neurological and psychiatric disorders | |
| KR101351454B1 (ko) | 위장 및 중추 신경계 장애의 치료에 유용한 입체이성질체 화합물의 합성 방법 및 중간 생성물 | |
| JP7048572B2 (ja) | テトラヒドロイソキノリンカッパーオピオイドアンタゴニスト | |
| EP1978959B1 (en) | Piperidine and piperazine derivatives | |
| BRPI0618971A2 (pt) | compostos derivados de isoqionolina e benzo [h] isoqionolina, composição farmacêutica, utilização dos compostos e processo de preparo dos compostos | |
| EP1434764B1 (en) | Process for obtainment of enantiomers-of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide; process for obtainment of non-racemic mixtures between the enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide; non racemic mixtures of enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide;pharmaceuticals compositions comprising said non-racemic mixtures of enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide | |
| HK1130053B (en) | 4-[(3-fluorophenoxy)phenylmethyl]piperidine methanesulfonate: uses, process of synthesis and pharmaceutical compositions | |
| HK1069818B (en) | Process for obtainment of enantiomers-of n-(2,6-dimethylphenyl)-1-propyl-2- piperidinocarboxamide; process for obtainment of non-racemic mixtures between the enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide; non racemic mixtures of enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide; pharmaceuticals compositions comprising said non-racemic mixtures of enantiomers of n-(2,6-dimethylphenyl)-1-propyl-2-piperidinocarboxamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110411 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110411 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130516 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130524 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20130618 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130618 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130823 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130917 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131015 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |