RU2407743C2 - Фармацевтические соединения - Google Patents
Фармацевтические соединения Download PDFInfo
- Publication number
- RU2407743C2 RU2407743C2 RU2008108623/04A RU2008108623A RU2407743C2 RU 2407743 C2 RU2407743 C2 RU 2407743C2 RU 2008108623/04 A RU2008108623/04 A RU 2008108623/04A RU 2008108623 A RU2008108623 A RU 2008108623A RU 2407743 C2 RU2407743 C2 RU 2407743C2
- Authority
- RU
- Russia
- Prior art keywords
- dihydrotetrabenazine
- psychosis
- cis
- compound
- isomer
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 100
- 238000000034 method Methods 0.000 claims abstract description 54
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 239000003814 drug Substances 0.000 claims description 38
- 208000004547 Hallucinations Diseases 0.000 claims description 33
- 208000024891 symptom Diseases 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 15
- 208000020925 Bipolar disease Diseases 0.000 claims description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 11
- 230000003542 behavioural effect Effects 0.000 claims description 11
- 206010012239 Delusion Diseases 0.000 claims description 10
- 231100000868 delusion Toxicity 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 9
- 230000002996 emotional effect Effects 0.000 claims description 9
- 201000006347 Intellectual Disability Diseases 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 206010019070 Hallucination, auditory Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 6
- 208000028683 bipolar I disease Diseases 0.000 claims description 6
- 230000003340 mental effect Effects 0.000 claims description 6
- 230000035807 sensation Effects 0.000 claims description 6
- 235000019615 sensations Nutrition 0.000 claims description 6
- 208000030507 AIDS Diseases 0.000 claims description 5
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 claims description 5
- 206010014418 Electrolyte imbalance Diseases 0.000 claims description 5
- 206010019075 Hallucination, visual Diseases 0.000 claims description 5
- 206010021402 Illogical thinking Diseases 0.000 claims description 5
- 206010024229 Leprosy Diseases 0.000 claims description 5
- 208000005647 Mumps Diseases 0.000 claims description 5
- 206010034719 Personality change Diseases 0.000 claims description 5
- 206010053632 Reactive psychosis Diseases 0.000 claims description 5
- 206010070863 Toxicity to various agents Diseases 0.000 claims description 5
- 230000006931 brain damage Effects 0.000 claims description 5
- 231100000874 brain damage Toxicity 0.000 claims description 5
- 208000029028 brain injury Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 201000004792 malaria Diseases 0.000 claims description 5
- 208000010805 mumps infectious disease Diseases 0.000 claims description 5
- 230000035943 smell Effects 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 235000019640 taste Nutrition 0.000 claims description 5
- 208000019206 urinary tract infection Diseases 0.000 claims description 5
- 206010033864 Paranoia Diseases 0.000 claims description 4
- 208000027099 Paranoid disease Diseases 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 41
- 230000000694 effects Effects 0.000 abstract description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- WEQLWGNDNRARGE-DJIMGWMZSA-N (2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-ol Chemical compound C1CN2C[C@@H](CC(C)C)[C@H](O)C[C@@H]2C2=C1C=C(OC)C(OC)=C2 WEQLWGNDNRARGE-DJIMGWMZSA-N 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 63
- 239000000203 mixture Substances 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 230000002829 reductive effect Effects 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 102000005962 receptors Human genes 0.000 description 32
- 108020003175 receptors Proteins 0.000 description 32
- 238000012360 testing method Methods 0.000 description 32
- 229940079593 drug Drugs 0.000 description 30
- 229960005333 tetrabenazine Drugs 0.000 description 29
- 241000700159 Rattus Species 0.000 description 28
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 28
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 28
- 150000001336 alkenes Chemical class 0.000 description 27
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 27
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000011534 incubation Methods 0.000 description 26
- 239000003446 ligand Substances 0.000 description 26
- 238000001914 filtration Methods 0.000 description 24
- 230000027455 binding Effects 0.000 description 23
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 18
- 230000009870 specific binding Effects 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 15
- 239000000164 antipsychotic agent Substances 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 239000000872 buffer Substances 0.000 description 14
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 13
- 229960003638 dopamine Drugs 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000004445 quantitative analysis Methods 0.000 description 13
- 239000002287 radioligand Substances 0.000 description 13
- 230000000638 stimulation Effects 0.000 description 13
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 238000004296 chiral HPLC Methods 0.000 description 11
- 208000010877 cognitive disease Diseases 0.000 description 11
- -1 hydroxyl ions Chemical class 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 208000028698 Cognitive impairment Diseases 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 229960001534 risperidone Drugs 0.000 description 10
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 229940005529 antipsychotics Drugs 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 229940127236 atypical antipsychotics Drugs 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 229960003878 haloperidol Drugs 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229940076279 serotonin Drugs 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229910000085 borane Inorganic materials 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000002424 x-ray crystallography Methods 0.000 description 6
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 5
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 5
- 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 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 239000003693 atypical antipsychotic agent Substances 0.000 description 5
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 238000006735 epoxidation reaction Methods 0.000 description 5
- 150000002118 epoxides Chemical class 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000007916 tablet composition Substances 0.000 description 5
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 101150049660 DRD2 gene Proteins 0.000 description 4
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- 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 4
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 238000012937 correction Methods 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001640 fractional crystallisation Methods 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 238000006197 hydroboration reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000010410 layer 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
- 230000014759 maintenance of location Effects 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 230000010004 neural pathway Effects 0.000 description 4
- 210000000118 neural pathway Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- MKJIEFSOBYUXJB-UHFFFAOYSA-N 9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2CC(CC(C)C)C(=O)CC2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 0 CC(C)C[C@@](CN(CCc1c2)C(C3)c1cc(OC)c2OC)*3O Chemical compound CC(C)C[C@@](CN(CCc1c2)C(C3)c1cc(OC)c2OC)*3O 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 3
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 102000009659 Vesicular Monoamine Transport Proteins Human genes 0.000 description 3
- 108010020033 Vesicular Monoamine Transport Proteins Proteins 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 230000000561 anti-psychotic effect Effects 0.000 description 3
- 238000009227 behaviour therapy Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000003930 cognitive ability Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229950002454 lysergide Drugs 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- 230000006403 short-term memory Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- JJYKJUXBWFATTE-SECBINFHSA-N (2r)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid Chemical compound CO[C@](C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-SECBINFHSA-N 0.000 description 2
- VAYOSLLFUXYJDT-QZGBZKRISA-N (6ar,9r)-n,n-diethyl-7-(tritritiomethyl)-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C([3H])([3H])[3H])C(=O)N(CC)CC)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-QZGBZKRISA-N 0.000 description 2
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 2
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 description 2
- 102000017910 Adrenergic receptor Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 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
- 230000019771 cognition Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000002050 diffraction method Methods 0.000 description 2
- 125000003700 epoxy group Chemical group 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000005153 frontal cortex Anatomy 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 2
- 229960003998 ifenprodil Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000015654 memory Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- SIIICDNNMDMWCI-YJNKXOJESA-N rti-55 Chemical compound C1([C@H]2C[C@@H]3CC[C@@H](N3C)[C@H]2C(=O)OC)=CC=C(I)C=C1 SIIICDNNMDMWCI-YJNKXOJESA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- ZZJYIKPMDIWRSN-TZBSWOFLSA-N (+)-butaclamol Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@@H]1CN1CC[C@@](C(C)(C)C)(O)C[C@@H]13 ZZJYIKPMDIWRSN-TZBSWOFLSA-N 0.000 description 1
- WEQLWGNDNRARGE-XIRDDKMYSA-N (2S,3S,11bS)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-ol Chemical compound C1CN2C[C@H](CC(C)C)[C@@H](O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 WEQLWGNDNRARGE-XIRDDKMYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WEQLWGNDNRARGE-BHYGNILZSA-N (2r,3s,11bs)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizin-2-ol Chemical compound C1CN2C[C@H](CC(C)C)[C@H](O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 WEQLWGNDNRARGE-BHYGNILZSA-N 0.000 description 1
- WEQLWGNDNRARGE-OIISXLGYSA-N (2s,3r,11br)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizin-2-ol Chemical compound C1CN2C[C@@H](CC(C)C)[C@@H](O)C[C@@H]2C2=C1C=C(OC)C(OC)=C2 WEQLWGNDNRARGE-OIISXLGYSA-N 0.000 description 1
- VSWBSWWIRNCQIJ-GJZGRUSLSA-N (R,R)-asenapine Chemical compound O1C2=CC=CC=C2[C@@H]2CN(C)C[C@H]2C2=CC(Cl)=CC=C21 VSWBSWWIRNCQIJ-GJZGRUSLSA-N 0.000 description 1
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- GWNKOGCQUQKSHT-UHFFFAOYSA-N 2,9,10-trimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizine Chemical compound COC1=C(OC)C=C2C3CC(OC)C(CC(C)C)CN3CCC2=C1 GWNKOGCQUQKSHT-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- PIVQQUNOTICCSA-UHFFFAOYSA-N ANTU Chemical compound C1=CC=C2C(NC(=S)N)=CC=CC2=C1 PIVQQUNOTICCSA-UHFFFAOYSA-N 0.000 description 1
- 206010001022 Acute psychosis Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OENMJNOSTJGSPT-GLUHHBOGSA-N CC(C)C[C@H](CN(CCC1C=C2OC)[C@H](C3)C1C=C2OC)[C@@H]3O Chemical compound CC(C)C[C@H](CN(CCC1C=C2OC)[C@H](C3)C1C=C2OC)[C@@H]3O OENMJNOSTJGSPT-GLUHHBOGSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008748 Chorea Diseases 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
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012241 Delusion of grandeur Diseases 0.000 description 1
- 102000003962 Dopamine D4 receptors Human genes 0.000 description 1
- 108090000357 Dopamine D4 receptors Proteins 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 208000027776 Extrapyramidal disease Diseases 0.000 description 1
- 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 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 208000000269 Hyperkinesis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101100510284 Rattus norvegicus Kl gene Proteins 0.000 description 1
- GOTMKOSCLKVOGG-UHFFFAOYSA-N SCH 23390 Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1=CC=CC=C1 GOTMKOSCLKVOGG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000004479 aerosol dispenser Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229960005245 asenapine Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- WEQLWGNDNRARGE-UHFFFAOYSA-N b-Dihydrotetrabenazine Chemical compound C1CN2CC(CC(C)C)C(O)CC2C2=C1C=C(OC)C(OC)=C2 WEQLWGNDNRARGE-UHFFFAOYSA-N 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 230000000903 blocking effect 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
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 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 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 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
- 208000018548 hypothalamic dysfunction Diseases 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 229960003162 iloperidone Drugs 0.000 description 1
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003924 mental process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000007433 nerve pathway Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 230000002360 prefrontal effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- BLGXFZZNTVWLAY-DIRVCLHFSA-N rauwolscine Chemical compound C1=CC=C2C(CCN3C[C@H]4CC[C@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-DIRVCLHFSA-N 0.000 description 1
- 230000006833 reintegration Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 230000021317 sensory perception Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0516167.4A GB0516167D0 (en) | 2005-08-06 | 2005-08-06 | Pharmaceutical compounds |
| GB0516167.4 | 2005-08-06 | ||
| GB0516790A GB0516790D0 (en) | 2005-08-16 | 2005-08-16 | Pharmaceutical compounds |
| GB0516790.3 | 2005-08-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2008108623A RU2008108623A (ru) | 2009-09-20 |
| RU2407743C2 true RU2407743C2 (ru) | 2010-12-27 |
Family
ID=37400949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008108623/04A RU2407743C2 (ru) | 2005-08-06 | 2006-08-04 | Фармацевтические соединения |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US20110257220A1 (enExample) |
| EP (2) | EP1855677B1 (enExample) |
| JP (1) | JP2009504622A (enExample) |
| KR (1) | KR20080033500A (enExample) |
| AT (2) | ATE415968T1 (enExample) |
| AU (1) | AU2006277753B2 (enExample) |
| CA (1) | CA2620960A1 (enExample) |
| CY (1) | CY1108843T1 (enExample) |
| DE (1) | DE602006004009D1 (enExample) |
| DK (1) | DK1855677T3 (enExample) |
| ES (1) | ES2318771T3 (enExample) |
| HR (1) | HRP20090074T3 (enExample) |
| MX (1) | MX2008001549A (enExample) |
| NZ (1) | NZ566011A (enExample) |
| PL (1) | PL1855677T3 (enExample) |
| PT (1) | PT1855677E (enExample) |
| RS (1) | RS50807B (enExample) |
| RU (1) | RU2407743C2 (enExample) |
| SI (1) | SI1855677T1 (enExample) |
| WO (1) | WO2007017654A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2783865C2 (ru) * | 2017-04-01 | 2022-11-21 | Адептио Фармасьютикалз Лимитед | Фармацевтические композиции |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2081929T3 (da) | 2006-11-08 | 2013-04-15 | Neurocrine Biosciences Inc | Substituerede 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11B-hexahydro-2H-pyrido[2,1-A]isoquinolin-2-ol-forbindelser og fremgangsmåder angående disse |
| US8008500B2 (en) | 2007-06-08 | 2011-08-30 | General Electric Company | Intermediates useful for making tetrabenazine compounds |
| US8053578B2 (en) | 2007-11-29 | 2011-11-08 | General Electric Company | Alpha-fluoroalkyl dihydrotetrabenazine imaging agents and probes |
| GB0810857D0 (en) * | 2008-06-13 | 2008-07-23 | Cambridge Lab Ireland Ltd | Pharmaceutical compounds |
| GB2463283A (en) * | 2008-09-08 | 2010-03-10 | Cambridge Lab | 3,11b-cis-dihydrotetrabenazine for use in treating asthma |
| GB2463451A (en) | 2008-09-08 | 2010-03-17 | Cambridge Lab | 3, 11b cis-dihydrotetrabenazine compounds for use in the treatment of dementia |
| CA2801061A1 (en) | 2010-06-01 | 2011-12-08 | Auspex Pharmaceuticals, Inc. | Benzoquinolone inhibitors of vmat2 |
| JP6010108B2 (ja) | 2011-04-01 | 2016-10-19 | スリーエム イノベイティブ プロパティズ カンパニー | トリアジン系紫外線吸収剤を含むフィルム |
| CA2936823A1 (en) | 2014-01-27 | 2015-07-30 | Auspex Pharmaceuticals, Inc. | Benzoquinoline inhibitors of vesicular monoamine transporter 2 |
| CA2938581C (en) | 2014-02-07 | 2023-02-28 | Neurocrine Biosciences, Inc. | Pharmaceutical compositions comprising an antipsychotic drug and a vmat2 inhibitor and uses thereof |
| IL284874B2 (en) | 2015-10-30 | 2023-10-01 | Neurocrine Biosciences Inc | Valbenazine salts and polymorphs thereof |
| LT3394057T (lt) | 2015-12-23 | 2022-06-27 | Neurocrine Biosciences, Inc. | Sintezės būdas, skirtas pagaminti (s)-(2r,3r,11br)-3-izobutil-9,10-dimetoksi-2,3,4,6,7,11b-heksahidro-1h-pirido[2,1-a]izochinolin-2-ilo 2-amino-3-metilbutanoato di(4-metilbenzensulfonatą) |
| TW202345829A (zh) * | 2016-12-02 | 2023-12-01 | 美商紐羅克里生物科學有限公司 | 戊苯那嗪（valbenazine）於治療精神分裂症或情感性精神分裂症之用途 |
| KR20230169457A (ko) | 2017-01-27 | 2023-12-15 | 뉴로크린 바이오사이언시즈 인코퍼레이티드 | 특정 vmat2 억제제의 투여 방법 |
| GB201705304D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705302D0 (en) * | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705303D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705306D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705305D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| RS66714B1 (sr) | 2017-09-21 | 2025-05-30 | Neurocrine Biosciences Inc | Formulacija visoke doze valbenazina i sastavi, postupci i kompleti povezani sa njim |
| MX2020003421A (es) | 2017-10-10 | 2020-07-20 | Neurocrine Biosciences Inc | Metodos para la administracion de ciertos inhibidores del transportador vesicular de monoamina 2 (vmat2). |
| KR20250070134A (ko) | 2017-10-10 | 2025-05-20 | 뉴로크린 바이오사이언시즈 인코퍼레이티드 | 특정 vmat2 억제제의 투여 방법 |
| GB201808464D0 (en) | 2018-05-23 | 2018-07-11 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compounds for use in treating huntington's disease |
| MA53239A (fr) | 2018-08-15 | 2022-05-04 | Neurocrine Biosciences Inc | Procédés d'administration de certains inhibiteurs de vmat2 |
| US10940141B1 (en) | 2019-08-23 | 2021-03-09 | Neurocrine Biosciences, Inc. | Methods for the administration of certain VMAT2 inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2073678C1 (ru) * | 1991-01-25 | 1997-02-20 | Ф.Хоффманн-Ля Рош Аг | (s)-1-[(10-хлор-6,7-дигидро-4-оксо-3-фенил-4h-бензо/а/хинолизин-1-ил)карбонил]-3-этоксипирролидин, (s)-1-[(10-хлор-6,7-дигидро-4-оксо-3-фенил-4h-бензо/а/хинолизин-1-ил)карбонил]-3-оксипирролидин в качестве промежуточного продукта, композиция, обладающая гипнотическим неседативным действием |
| WO1999021856A1 (fr) * | 1997-10-28 | 1999-05-06 | Pierre Fabre Medicament | Derives d'aminomethyl-benzo[a]quinolizidine, leur preparation et leur application en therapeutique pour les maladies neurodegeneratives |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2830993A (en) * | 1958-04-15 | Quinolizine derivatives | ||
| US2843591A (en) | 1958-07-15 | Method for preparing same | ||
| US6087376A (en) * | 1997-02-05 | 2000-07-11 | University Of Kentucky Research Foundation | Use of lobeline compounds in the treatment of central nervous system diseases and pathologies |
| GB2410947B (en) * | 2004-02-11 | 2008-09-17 | Cambridge Lab Ltd | Pharmaceutical compounds |
-
2006
- 2006-08-04 AT AT06765238T patent/ATE415968T1/de active
- 2006-08-04 CA CA002620960A patent/CA2620960A1/en not_active Abandoned
- 2006-08-04 PT PT06765238T patent/PT1855677E/pt unknown
- 2006-08-04 JP JP2008525620A patent/JP2009504622A/ja not_active Ceased
- 2006-08-04 KR KR1020087005308A patent/KR20080033500A/ko not_active Withdrawn
- 2006-08-04 MX MX2008001549A patent/MX2008001549A/es active IP Right Grant
- 2006-08-04 RU RU2008108623/04A patent/RU2407743C2/ru not_active IP Right Cessation
- 2006-08-04 PL PL06765238T patent/PL1855677T3/pl unknown
- 2006-08-04 EP EP06765238A patent/EP1855677B1/en active Active
- 2006-08-04 DE DE602006004009T patent/DE602006004009D1/de active Active
- 2006-08-04 US US11/997,591 patent/US20110257220A1/en not_active Abandoned
- 2006-08-04 HR HR20090074T patent/HRP20090074T3/xx unknown
- 2006-08-04 SI SI200630210T patent/SI1855677T1/sl unknown
- 2006-08-04 ES ES06765238T patent/ES2318771T3/es active Active
- 2006-08-04 DK DK06765238T patent/DK1855677T3/da active
- 2006-08-04 AU AU2006277753A patent/AU2006277753B2/en not_active Expired - Fee Related
- 2006-08-04 WO PCT/GB2006/002936 patent/WO2007017654A1/en not_active Ceased
- 2006-08-04 RS RSP-2009/0055A patent/RS50807B/sr unknown
- 2006-08-04 NZ NZ566011A patent/NZ566011A/en not_active IP Right Cessation
- 2006-08-04 AT AT08170385T patent/ATE534391T1/de active
- 2006-08-04 EP EP08170385A patent/EP2050451B1/en active Active
-
2009
- 2009-02-26 CY CY20091100221T patent/CY1108843T1/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2073678C1 (ru) * | 1991-01-25 | 1997-02-20 | Ф.Хоффманн-Ля Рош Аг | (s)-1-[(10-хлор-6,7-дигидро-4-оксо-3-фенил-4h-бензо/а/хинолизин-1-ил)карбонил]-3-этоксипирролидин, (s)-1-[(10-хлор-6,7-дигидро-4-оксо-3-фенил-4h-бензо/а/хинолизин-1-ил)карбонил]-3-оксипирролидин в качестве промежуточного продукта, композиция, обладающая гипнотическим неседативным действием |
| WO1999021856A1 (fr) * | 1997-10-28 | 1999-05-06 | Pierre Fabre Medicament | Derives d'aminomethyl-benzo[a]quinolizidine, leur preparation et leur application en therapeutique pour les maladies neurodegeneratives |
Non-Patent Citations (1)
| Title |
|---|
| MEHVAR R, JORNAL OF PHARMACEUTICAL SCIENCES, vol.76, no.6, 1987, pages 461-465. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2783865C2 (ru) * | 2017-04-01 | 2022-11-21 | Адептио Фармасьютикалз Лимитед | Фармацевтические композиции |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2620960A1 (en) | 2007-02-15 |
| CY1108843T1 (el) | 2014-07-02 |
| DK1855677T3 (da) | 2009-02-09 |
| RU2008108623A (ru) | 2009-09-20 |
| ES2318771T3 (es) | 2009-05-01 |
| RS50807B (sr) | 2010-08-31 |
| EP1855677B1 (en) | 2008-12-03 |
| HRP20090074T3 (en) | 2009-04-30 |
| PL1855677T3 (pl) | 2009-07-31 |
| AU2006277753B2 (en) | 2011-11-10 |
| SI1855677T1 (sl) | 2009-04-30 |
| AU2006277753A1 (en) | 2007-02-15 |
| KR20080033500A (ko) | 2008-04-16 |
| PT1855677E (pt) | 2009-01-13 |
| WO2007017654A1 (en) | 2007-02-15 |
| EP2050451B1 (en) | 2011-11-23 |
| DE602006004009D1 (de) | 2009-01-15 |
| MX2008001549A (es) | 2008-04-04 |
| EP1855677A1 (en) | 2007-11-21 |
| HK1111083A1 (en) | 2008-08-01 |
| JP2009504622A (ja) | 2009-02-05 |
| EP2050451A1 (en) | 2009-04-22 |
| NZ566011A (en) | 2011-01-28 |
| ATE415968T1 (de) | 2008-12-15 |
| ATE534391T1 (de) | 2011-12-15 |
| US20110257220A1 (en) | 2011-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2050451B1 (en) | 3,11b cis dihydrotetrabanezine for the treatment of psychoses | |
| EP0734724B1 (en) | Process for the preparation of a phencynonate hydrochloride of alpha-configuration | |
| GB2463452A (en) | Desmethyl derivatives of tetrabenazine and pharmaceutical compositions thereof | |
| EP1885363B1 (en) | Use of 3,11b-cis-dihydrotetrabenazine for the treatment of symptoms of huntington' s disease | |
| JP2007522193A (ja) | ジヒドロテトラベナジン類およびそれらを含有する医薬組成物 | |
| GB2463451A (en) | 3, 11b cis-dihydrotetrabenazine compounds for use in the treatment of dementia | |
| CN110664801A (zh) | 用于治疗痴呆中的激越行为的包含右美沙芬化合物和奎尼丁的药物组合物 | |
| CN101932323A (zh) | 3，11b-顺式-二氢丁苯那嗪在治疗多发性硬化症以及自身免疫性脊髓炎中的用途 | |
| KR20230096003A (ko) | 만성 ssri 레지멘 후 실로시빈에 대한 민감도를 증가시키기 위한 벤조디아제핀의 사용 | |
| WO2009150474A1 (en) | Dihydrotetrabenanzine for the treatment of anxiety | |
| HK1125575A (en) | 3,11b cis dihydrotetrabanezine for the treatment of psychoses | |
| HK1111083B (en) | 3,11b cis dihydrotetrabanezine for the treatment of schizophrenia and other psychoses | |
| CN101351205A (zh) | 治疗精神分裂症及其它精神病的3,11b-顺式-二氢丁苯那嗪 | |
| CN101646676A (zh) | 7,8-饱和-4,5-环氧-吗啡烷离子类似物的(s)-n-立体异构体 | |
| HK40071167A (en) | Methods for treating behavioral and psychological symptoms in patients with dementia | |
| CN114761008A (zh) | 用于在患有痴呆的患者中治疗行为和心理症状的方法 | |
| HK1111085B (en) | Use of 3,11b-cis-dihydrotetrabenazine for the treatment of symptoms of huntington' s disease | |
| HK1121972A (en) | Use of 3,11b-cis-dihydrotetrabenazine for the treatment of symptoms of huntington's disease | |
| HK40020899A (en) | Pharmaceutical compositions comprising a dextromethorphan compound and quinidine for the treatment of agitation in dementia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20120805 |