NO310660B1 - Kondenserte tiazolderivater med 5-HT-reseptor-affinitet, anvendelse og fremstilling derav samt farmasöytisk blanding - Google Patents
Kondenserte tiazolderivater med 5-HT-reseptor-affinitet, anvendelse og fremstilling derav samt farmasöytisk blanding Download PDFInfo
- Publication number
- NO310660B1 NO310660B1 NO19976157A NO976157A NO310660B1 NO 310660 B1 NO310660 B1 NO 310660B1 NO 19976157 A NO19976157 A NO 19976157A NO 976157 A NO976157 A NO 976157A NO 310660 B1 NO310660 B1 NO 310660B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compounds
- mixture
- compound
- halogen
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 title description 7
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 title description 2
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 title 1
- 150000007979 thiazole derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 148
- 239000000203 mixture Substances 0.000 claims description 118
- 239000002904 solvent Substances 0.000 claims description 65
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 208000011117 substance-related disease Diseases 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
- 206010013654 Drug abuse Diseases 0.000 claims description 6
- 208000030814 Eating disease Diseases 0.000 claims description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 206010033664 Panic attack Diseases 0.000 claims description 6
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 206010039966 Senile dementia Diseases 0.000 claims description 6
- 206010041250 Social phobia Diseases 0.000 claims description 6
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
- 208000022531 anorexia Diseases 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 206010061428 decreased appetite Diseases 0.000 claims description 6
- 235000014632 disordered eating Nutrition 0.000 claims description 6
- 206010013663 drug dependence Diseases 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 208000019906 panic disease Diseases 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- BKCZXQQTZPBRPV-UHFFFAOYSA-N 3-(1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=CC=C2C(C3=CSC=4N3CCN=4)=CSC2=C1 BKCZXQQTZPBRPV-UHFFFAOYSA-N 0.000 claims description 4
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- SCNGAEDAPSRYOR-UHFFFAOYSA-N 3-(1-benzofuran-3-yl)-6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidine Chemical compound C1=CC=C2C(C3=CSC4=NCCCN43)=COC2=C1 SCNGAEDAPSRYOR-UHFFFAOYSA-N 0.000 claims description 3
- KFGPZSUBOWPPMR-UHFFFAOYSA-N 3-(1-benzothiophen-3-yl)-6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidine Chemical compound C1=CC=C2C(C3=CSC4=NCCCN43)=CSC2=C1 KFGPZSUBOWPPMR-UHFFFAOYSA-N 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- IPJUOWGTGHKFKN-UHFFFAOYSA-N 1-benzothiophene-5-carbonitrile Chemical compound N#CC1=CC=C2SC=CC2=C1 IPJUOWGTGHKFKN-UHFFFAOYSA-N 0.000 claims description 2
- SRYQCAVJRROBBI-UHFFFAOYSA-N 3-(5-chloro-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C12=CC(Cl)=CC=C2SC=C1C1=CSC2=NCCN12 SRYQCAVJRROBBI-UHFFFAOYSA-N 0.000 claims description 2
- AFAQYJGEWASWLG-UHFFFAOYSA-N 3-(5-fluoro-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C12=CC(F)=CC=C2SC=C1C1=CSC2=NCCN12 AFAQYJGEWASWLG-UHFFFAOYSA-N 0.000 claims description 2
- GMPXFKLYBVWGLP-UHFFFAOYSA-N 3-(5-methoxy-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C12=CC(OC)=CC=C2SC=C1C1=CSC2=NCCN12 GMPXFKLYBVWGLP-UHFFFAOYSA-N 0.000 claims description 2
- 231100000867 compulsive behavior Toxicity 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- IPZFRXRLIVTZIX-UHFFFAOYSA-N 3-(1-benzofuran-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=CC=C2C(C3=CSC=4N3CCN=4)=COC2=C1 IPZFRXRLIVTZIX-UHFFFAOYSA-N 0.000 claims 1
- 240000001987 Pyrus communis Species 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 138
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 79
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 239000007787 solid Substances 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 229910052757 nitrogen Inorganic materials 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- 238000001914 filtration Methods 0.000 description 23
- 235000019198 oils Nutrition 0.000 description 23
- 238000010992 reflux Methods 0.000 description 16
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 9
- 239000002775 capsule Substances 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- ZEVUHRJDTWDODR-UHFFFAOYSA-N 4-chlorobut-2-ynoxybenzene Chemical compound ClCC#CCOC1=CC=CC=C1 ZEVUHRJDTWDODR-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 210000001519 tissue Anatomy 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000006186 oral dosage form Substances 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- CHGABJRZTFUHDT-UHFFFAOYSA-N 1-(1-benzofuran-3-yl)ethanone Chemical compound C1=CC=C2C(C(=O)C)=COC2=C1 CHGABJRZTFUHDT-UHFFFAOYSA-N 0.000 description 5
- CKHWNGWAHFLCTJ-UHFFFAOYSA-N 1-(1-benzothiophen-3-yl)-2-bromoethanone Chemical compound C1=CC=C2C(C(=O)CBr)=CSC2=C1 CKHWNGWAHFLCTJ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- WVHFTONHSRLBGL-UHFFFAOYSA-N 1-(1-benzofuran-3-yl)-2-bromoethanone Chemical compound C1=CC=C2C(C(=O)CBr)=COC2=C1 WVHFTONHSRLBGL-UHFFFAOYSA-N 0.000 description 4
- FNTIAKACFVIIAI-UHFFFAOYSA-N 1-(5-methoxy-1-benzothiophen-3-yl)ethanone Chemical compound COC1=CC=C2SC=C(C(C)=O)C2=C1 FNTIAKACFVIIAI-UHFFFAOYSA-N 0.000 description 4
- QPNDSJGVDOIAGS-UHFFFAOYSA-N 1-(5-methoxy-2,3-dihydro-1-benzothiophen-3-yl)-2-phenoxyethanone Chemical compound C12=CC(OC)=CC=C2SCC1C(=O)COC1=CC=CC=C1 QPNDSJGVDOIAGS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- -1 bicarbonate salt Chemical class 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000002702 enteric coating Substances 0.000 description 4
- 238000009505 enteric coating Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000010438 heat treatment Methods 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
- 239000006201 parenteral dosage form Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- VUWDKOQPKHAVSN-UHFFFAOYSA-N 1-(5-fluoro-1-benzothiophen-3-yl)ethanone Chemical compound C1=C(F)C=C2C(C(=O)C)=CSC2=C1 VUWDKOQPKHAVSN-UHFFFAOYSA-N 0.000 description 3
- LTNIYZOLKCPNHY-UHFFFAOYSA-N 1-methoxy-4-(4-phenoxybut-2-ynylsulfanyl)benzene Chemical compound C1=CC(OC)=CC=C1SCC#CCOC1=CC=CC=C1 LTNIYZOLKCPNHY-UHFFFAOYSA-N 0.000 description 3
- GIUVHXVCSSHIQJ-UHFFFAOYSA-N 1-methoxy-4-(4-phenoxybut-2-ynylsulfinyl)benzene Chemical compound C1=CC(OC)=CC=C1S(=O)CC#CCOC1=CC=CC=C1 GIUVHXVCSSHIQJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
- 239000012839 Krebs-Henseleit buffer Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000005567 liquid scintillation counting Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- NVHNGVXBCWYLFA-UHFFFAOYSA-N 1,3-diazinane-2-thione Chemical compound S=C1NCCCN1 NVHNGVXBCWYLFA-UHFFFAOYSA-N 0.000 description 2
- RCHDLEVSZBOHOS-UHFFFAOYSA-N 1,4-dichlorobut-2-yne Chemical compound ClCC#CCCl RCHDLEVSZBOHOS-UHFFFAOYSA-N 0.000 description 2
- ZTTZKDDWXHQKSY-UHFFFAOYSA-N 1-(1-benzothiophen-3-yl)ethanone Chemical compound C1=CC=C2C(C(=O)C)=CSC2=C1 ZTTZKDDWXHQKSY-UHFFFAOYSA-N 0.000 description 2
- GMBFNZCPZFVKAT-UHFFFAOYSA-N 1-(2-methoxyphenyl)propan-2-one Chemical compound COC1=CC=CC=C1CC(C)=O GMBFNZCPZFVKAT-UHFFFAOYSA-N 0.000 description 2
- XDMSMJRHOBFWDD-UHFFFAOYSA-N 1-(5-chloro-1-benzothiophen-3-yl)ethanone Chemical compound C1=C(Cl)C=C2C(C(=O)C)=CSC2=C1 XDMSMJRHOBFWDD-UHFFFAOYSA-N 0.000 description 2
- IANOSQWTPMGMRD-UHFFFAOYSA-N 1-(5-chloro-2,3-dihydro-1-benzothiophen-3-yl)-2-phenoxyethanone Chemical compound C12=CC(Cl)=CC=C2SCC1C(=O)COC1=CC=CC=C1 IANOSQWTPMGMRD-UHFFFAOYSA-N 0.000 description 2
- TYODVCQLVRMAFD-UHFFFAOYSA-N 1-(5-fluoro-2,3-dihydro-1-benzothiophen-3-yl)-2-phenoxyethanone Chemical compound C12=CC(F)=CC=C2SCC1C(=O)COC1=CC=CC=C1 TYODVCQLVRMAFD-UHFFFAOYSA-N 0.000 description 2
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
- DOPYAYKQUNDJOP-UHFFFAOYSA-N 1-chloro-4-(4-phenoxybut-2-ynylsulfanyl)benzene Chemical compound C1=CC(Cl)=CC=C1SCC#CCOC1=CC=CC=C1 DOPYAYKQUNDJOP-UHFFFAOYSA-N 0.000 description 2
- CLNLGJLYFRTHPQ-UHFFFAOYSA-N 1-chloro-4-(4-phenoxybut-2-ynylsulfinyl)benzene Chemical compound C1=CC(Cl)=CC=C1S(=O)CC#CCOC1=CC=CC=C1 CLNLGJLYFRTHPQ-UHFFFAOYSA-N 0.000 description 2
- XYLOXXJTIYJSSO-UHFFFAOYSA-N 1-fluoro-4-(4-phenoxybut-2-ynylsulfanyl)benzene Chemical compound C1=CC(F)=CC=C1SCC#CCOC1=CC=CC=C1 XYLOXXJTIYJSSO-UHFFFAOYSA-N 0.000 description 2
- CCABJUHDHUCPDQ-UHFFFAOYSA-N 2-bromo-1-(5-chloro-1-benzothiophen-3-yl)ethanone Chemical compound ClC1=CC=C2SC=C(C(=O)CBr)C2=C1 CCABJUHDHUCPDQ-UHFFFAOYSA-N 0.000 description 2
- FZKABEQVVYVJCI-UHFFFAOYSA-N 3-(2-bromoacetyl)-1-benzothiophene-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(C(=O)CBr)=CSC2=C1 FZKABEQVVYVJCI-UHFFFAOYSA-N 0.000 description 2
- NIMMQYIFSIQSEK-UHFFFAOYSA-N 3-(2-phenoxyacetyl)-2,3-dihydro-1-benzothiophene-5-carbonitrile Chemical compound C1SC2=CC=C(C#N)C=C2C1C(=O)COC1=CC=CC=C1 NIMMQYIFSIQSEK-UHFFFAOYSA-N 0.000 description 2
- NAMJNARZYSZZDF-UHFFFAOYSA-N 3-acetyl-1-benzothiophene-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(C(=O)C)=CSC2=C1 NAMJNARZYSZZDF-UHFFFAOYSA-N 0.000 description 2
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 210000005257 cortical tissue Anatomy 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 230000012154 norepinephrine uptake Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000013275 serotonin uptake Effects 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 210000003568 synaptosome Anatomy 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- KAVTVUFNMHWAPD-UHFFFAOYSA-N 1-methoxy-4-[4-(4-methoxyphenyl)sulfanylbut-2-ynylsulfanyl]benzene Chemical compound C1=CC(OC)=CC=C1SCC#CCSC1=CC=C(OC)C=C1 KAVTVUFNMHWAPD-UHFFFAOYSA-N 0.000 description 1
- DZRDRAPINZWTEW-UHFFFAOYSA-N 2-hydroxy-3-methylidene-2-(phenoxymethyl)-1-benzothiophene-5-carbonitrile Chemical compound S1C2=CC=C(C#N)C=C2C(=C)C1(O)COC1=CC=CC=C1 DZRDRAPINZWTEW-UHFFFAOYSA-N 0.000 description 1
- FUMGEMIVASIFPY-UHFFFAOYSA-N 3-(1-benzofuran-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrate;hydrobromide Chemical compound O.Br.C1=CC=C2C(C3=CSC=4N3CCN=4)=COC2=C1 FUMGEMIVASIFPY-UHFFFAOYSA-N 0.000 description 1
- MDSOHNACNBSJKF-UHFFFAOYSA-N 3-(1-benzofuran-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrobromide Chemical compound Br.C1=CC=C2C(C3=CSC=4N3CCN=4)=COC2=C1 MDSOHNACNBSJKF-UHFFFAOYSA-N 0.000 description 1
- VWVYQLZROJLOIV-UHFFFAOYSA-N 3-(1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;dihydrate;hydrobromide Chemical compound O.O.Br.C1=CC=C2C(C3=CSC=4N3CCN=4)=CSC2=C1 VWVYQLZROJLOIV-UHFFFAOYSA-N 0.000 description 1
- BRGSVUWOWIJVKR-UHFFFAOYSA-N 3-(5,6-dihydroimidazo[2,1-b][1,3]thiazol-3-yl)-1-benzothiophene-5-carbonitrile;hydrobromide Chemical compound Br.C12=CC(C#N)=CC=C2SC=C1C1=CSC2=NCCN12 BRGSVUWOWIJVKR-UHFFFAOYSA-N 0.000 description 1
- ZVODWIWUVBWJLY-UHFFFAOYSA-N 3-(5-chloro-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrobromide Chemical compound Br.C12=CC(Cl)=CC=C2SC=C1C1=CSC2=NCCN12 ZVODWIWUVBWJLY-UHFFFAOYSA-N 0.000 description 1
- CQCNILGHVQIVEY-UHFFFAOYSA-N 3-(5-fluoro-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrobromide Chemical compound Br.C12=CC(F)=CC=C2SC=C1C1=CSC2=NCCN12 CQCNILGHVQIVEY-UHFFFAOYSA-N 0.000 description 1
- RLZUSORQJSFUNC-UHFFFAOYSA-N 3-(5-methoxy-1-benzothiophen-3-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrobromide Chemical compound Br.C12=CC(OC)=CC=C2SC=C1C1=CSC2=NCCN12 RLZUSORQJSFUNC-UHFFFAOYSA-N 0.000 description 1
- YHENUSABKJDJKN-UHFFFAOYSA-N 4-(4-phenoxybut-2-ynylsulfanyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1SCC#CCOC1=CC=CC=C1 YHENUSABKJDJKN-UHFFFAOYSA-N 0.000 description 1
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- MVPUXVBBHWUOFS-UHFFFAOYSA-N 4-sulfanylbenzonitrile Chemical compound SC1=CC=C(C#N)C=C1 MVPUXVBBHWUOFS-UHFFFAOYSA-N 0.000 description 1
- JDAYLYMYNKIHMN-UHFFFAOYSA-N 5-chloro-3-methylidene-2-(phenoxymethyl)-1-benzothiophen-2-ol Chemical compound S1C2=CC=C(Cl)C=C2C(=C)C1(O)COC1=CC=CC=C1 JDAYLYMYNKIHMN-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- UHIMBGSYHAETGG-UHFFFAOYSA-N 5-methoxy-3-methylidene-2-(phenoxymethyl)-1-benzothiophen-2-ol Chemical compound C=C1C2=CC(OC)=CC=C2SC1(O)COC1=CC=CC=C1 UHIMBGSYHAETGG-UHFFFAOYSA-N 0.000 description 1
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241001480079 Corymbia calophylla Species 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000017911 HTR1A Human genes 0.000 description 1
- 101150015707 HTR1A gene Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 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
- 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 150000002462 imidazolines Chemical class 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- BCXCABRDBBWWGY-UHFFFAOYSA-N n-benzyl-n-methylprop-2-yn-1-amine;hydrochloride Chemical compound Cl.C#CCN(C)CC1=CC=CC=C1 BCXCABRDBBWWGY-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000000966 norepinephrine reuptake Effects 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000019809 paraffin wax Nutrition 0.000 description 1
- 229960004239 pargyline hydrochloride Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Substances C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- WZMPOCLULGAHJR-UHFFFAOYSA-N thiophen-2-ol Chemical compound OC1=CC=CS1 WZMPOCLULGAHJR-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 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
- 230000009466 transformation Effects 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
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/24—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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Anesthesiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9513467.2A GB9513467D0 (en) | 1995-07-01 | 1995-07-01 | Therapeutic agents |
| PCT/EP1996/002676 WO1997002269A1 (fr) | 1995-07-01 | 1996-06-20 | Derives thiazoles condenses possedant une affinite pour les recepteurs 5-ht |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO976157L NO976157L (no) | 1997-12-30 |
| NO976157D0 NO976157D0 (no) | 1997-12-30 |
| NO310660B1 true NO310660B1 (no) | 2001-08-06 |
Family
ID=10777016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19976157A NO310660B1 (no) | 1995-07-01 | 1997-12-30 | Kondenserte tiazolderivater med 5-HT-reseptor-affinitet, anvendelse og fremstilling derav samt farmasöytisk blanding |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US5869492A (fr) |
| EP (1) | EP0836606B1 (fr) |
| JP (1) | JPH11508568A (fr) |
| KR (1) | KR19990028619A (fr) |
| CN (1) | CN1064966C (fr) |
| AR (1) | AR003963A1 (fr) |
| AT (1) | ATE195942T1 (fr) |
| AU (1) | AU708789B2 (fr) |
| BG (1) | BG63206B1 (fr) |
| BR (1) | BR9609525A (fr) |
| CA (1) | CA2222725A1 (fr) |
| CO (1) | CO4700463A1 (fr) |
| CZ (1) | CZ376297A3 (fr) |
| DE (1) | DE69610104T2 (fr) |
| DK (1) | DK0836606T3 (fr) |
| ES (1) | ES2151175T3 (fr) |
| GB (1) | GB9513467D0 (fr) |
| GR (1) | GR3034397T3 (fr) |
| HR (1) | HRP960306B1 (fr) |
| HU (1) | HUP9901258A3 (fr) |
| IL (1) | IL122158A (fr) |
| NO (1) | NO310660B1 (fr) |
| NZ (1) | NZ312130A (fr) |
| PL (1) | PL324337A1 (fr) |
| PT (1) | PT836606E (fr) |
| SK (1) | SK179297A3 (fr) |
| TR (1) | TR199701756T1 (fr) |
| TW (1) | TW474939B (fr) |
| WO (1) | WO1997002269A1 (fr) |
| ZA (1) | ZA965494B (fr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9705428D0 (en) | 1997-03-15 | 1997-04-30 | Knoll Ag | Therapeutic agents |
| RU2186065C1 (ru) * | 1998-03-31 | 2002-07-27 | Сионоги Энд Ко., Лтд. | Способ получения производных 5-гидрокси-бензо[b]тиофен-3-карбоновой кислоты (варианты) и производные бензо[b]тиофеновой кислоты |
| DE19908536A1 (de) | 1999-02-26 | 2000-08-31 | Aventis Pharma Gmbh | Polycyclische Thiazol-2-yliden Amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| GB9911881D0 (en) * | 1999-05-21 | 1999-07-21 | Knoll Ag | Therapeutic agents |
| GB9911863D0 (en) * | 1999-05-21 | 1999-07-21 | Knoll Ag | Therapeutic agents |
| GB0005789D0 (en) | 2000-03-11 | 2000-05-03 | Knoll Ag | Therapeutic agents |
| GB0023610D0 (en) * | 2000-09-27 | 2000-11-08 | Knoll Ag | Therapeutic agents |
| DE10112197A1 (de) * | 2001-03-14 | 2002-09-19 | Gruenenthal Gmbh | Substituierte Pyrazolo- und Thiazolopyrimidine |
| US8106074B2 (en) | 2001-07-13 | 2012-01-31 | Pierre Fabre Medicament | Pyridin-2-yl-methylamine derivatives for treating opiate dependence |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0002400A1 (fr) * | 1977-11-24 | 1979-06-13 | Synthelabo | Dérivés de thiazole, leur préparation, intermédiaires et leur application en thérapeutique |
| DK0672043T3 (da) * | 1992-07-13 | 2001-08-27 | Janssen Pharmaceutica Nv | Hidtil ukendte 4-(3-benzofuranyl)-piperidinyl- og 4-(3-benzothienyl)-piperidinyl-derivater og farmaceutiske præparater indeholdende dem |
-
1995
- 1995-07-01 GB GBGB9513467.2A patent/GB9513467D0/en active Pending
-
1996
- 1996-06-20 CA CA002222725A patent/CA2222725A1/fr not_active Abandoned
- 1996-06-20 NZ NZ312130A patent/NZ312130A/xx unknown
- 1996-06-20 KR KR1019970709941A patent/KR19990028619A/ko not_active Application Discontinuation
- 1996-06-20 PL PL96324337A patent/PL324337A1/xx unknown
- 1996-06-20 EP EP96922862A patent/EP0836606B1/fr not_active Expired - Lifetime
- 1996-06-20 HU HU9901258A patent/HUP9901258A3/hu unknown
- 1996-06-20 AU AU63589/96A patent/AU708789B2/en not_active Ceased
- 1996-06-20 AT AT96922862T patent/ATE195942T1/de not_active IP Right Cessation
- 1996-06-20 TR TR97/01756T patent/TR199701756T1/xx unknown
- 1996-06-20 PT PT96922862T patent/PT836606E/pt unknown
- 1996-06-20 SK SK1792-97A patent/SK179297A3/sk unknown
- 1996-06-20 ES ES96922862T patent/ES2151175T3/es not_active Expired - Lifetime
- 1996-06-20 WO PCT/EP1996/002676 patent/WO1997002269A1/fr not_active Application Discontinuation
- 1996-06-20 BR BR9609525A patent/BR9609525A/pt not_active Application Discontinuation
- 1996-06-20 DK DK96922862T patent/DK0836606T3/da active
- 1996-06-20 JP JP9504758A patent/JPH11508568A/ja active Pending
- 1996-06-20 IL IL12215896A patent/IL122158A/xx not_active IP Right Cessation
- 1996-06-20 US US08/973,960 patent/US5869492A/en not_active Expired - Fee Related
- 1996-06-20 CZ CZ973762A patent/CZ376297A3/cs unknown
- 1996-06-20 DE DE69610104T patent/DE69610104T2/de not_active Expired - Fee Related
- 1996-06-20 CN CN961952377A patent/CN1064966C/zh not_active Expired - Fee Related
- 1996-06-27 TW TW085107723A patent/TW474939B/zh active
- 1996-06-28 ZA ZA9605494A patent/ZA965494B/xx unknown
- 1996-07-01 HR HR960306A patent/HRP960306B1/xx not_active IP Right Cessation
- 1996-07-01 AR ARP960103406A patent/AR003963A1/es unknown
- 1996-07-02 CO CO96034464A patent/CO4700463A1/es unknown
-
1997
- 1997-11-28 BG BG102084A patent/BG63206B1/bg unknown
- 1997-12-30 NO NO19976157A patent/NO310660B1/no unknown
-
2000
- 2000-09-13 GR GR20000402087T patent/GR3034397T3/el not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0970090B1 (fr) | 4-arylmethylene-2-imino-2,3-dihydrothiazoles substitues, leurs derives, et leur utilisation pharmaceutique | |
| AU5065700A (en) | Thiazoloderivatives and pharmaceutical compositions containing them | |
| US6900216B2 (en) | Dihydroimidazo[2,1-b]thiazole and dihydro-5h-thiazolo[3,2-A]pyrimidines as antidepressant agents | |
| AU4565200A (en) | Substituted imidazothiazoles as antidepressant agents | |
| NO310660B1 (no) | Kondenserte tiazolderivater med 5-HT-reseptor-affinitet, anvendelse og fremstilling derav samt farmasöytisk blanding | |
| RU2169147C2 (ru) | ПРОИЗВОДНЫЕ АМИДОВ КАРБОНОВЫХ КИСЛОТ С ГЕТЕРОЦИКЛИЧЕСКИМИ ЗАМЕСТИТЕЛЯМИ И КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ СПОСОБНОСТЬЮ ИНГИБИРОВАТЬ 5-HT1А, И/ИЛИ α1, И/ИЛИ α2A, И/ИЛИ α2D, И/ИЛИ D2 РЕЦЕПТОРЫ | |
| WO2002026747A1 (fr) | Derives de dihydroimidazo[2,1-b]thiazole et de dihydro-5h-thiazolo[3,2-a]pyrimidine possedant une affinite pour les recepteurs 5-ht | |
| MXPA97009509A (en) | Therapeutic agents | |
| MXPA99005997A (en) | Sulfonamide compounds having 5-ht receptor activity | |
| CZ9903260A3 (cs) | Terapeutická činidla |