NO174507B - Analogifremgangsmaate for fremstilling av terapeutisk aktive substiuerte benzazepiner - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive substiuerte benzazepiner Download PDFInfo
- Publication number
- NO174507B NO174507B NO885096A NO885096A NO174507B NO 174507 B NO174507 B NO 174507B NO 885096 A NO885096 A NO 885096A NO 885096 A NO885096 A NO 885096A NO 174507 B NO174507 B NO 174507B
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- chloro
- tetrahydro
- formula
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 150000008038 benzoazepines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 187
- -1 1-substituted-2,3,4,5-tetrahydro-1H-3-benzazepines Chemical class 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 89
- 239000000460 chlorine Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 14
- 230000009467 reduction Effects 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000002785 azepinyl group Chemical group 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 230000008030 elimination Effects 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 230000026030 halogenation Effects 0.000 claims description 3
- 238000005658 halogenation reaction Methods 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- FKWYOTLPGSGDTP-UHFFFAOYSA-N 8-chloro-3-methyl-5-(2,2,2-trifluoroethoxy)-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound FC(F)(F)COC1CN(C)CCC2=CC(Cl)=C(O)C=C21 FKWYOTLPGSGDTP-UHFFFAOYSA-N 0.000 claims description 2
- XVCTVHVYHVASIP-UHFFFAOYSA-N 8-chloro-3-methyl-5-(2-phenylethoxy)-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1OCCC1=CC=CC=C1 XVCTVHVYHVASIP-UHFFFAOYSA-N 0.000 claims description 2
- QIRXFZBPQOTDCU-UHFFFAOYSA-N 8-chloro-3-methyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1OC1=CC=CC=C1 QIRXFZBPQOTDCU-UHFFFAOYSA-N 0.000 claims description 2
- BWUDJJGJDCRQNH-UHFFFAOYSA-N 8-chloro-3-methyl-5-phenylmethoxy-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1OCC1=CC=CC=C1 BWUDJJGJDCRQNH-UHFFFAOYSA-N 0.000 claims description 2
- GYHGYVBXMMJZRX-UHFFFAOYSA-N 8-chloro-3-methyl-5-phenylsulfanyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1SC1=CC=CC=C1 GYHGYVBXMMJZRX-UHFFFAOYSA-N 0.000 claims description 2
- KMGQNUYJWJFJQG-UHFFFAOYSA-N 8-chloro-3-methyl-5-piperidin-1-yl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1N1CCCCC1 KMGQNUYJWJFJQG-UHFFFAOYSA-N 0.000 claims description 2
- XINWVWPVSCGKJU-UHFFFAOYSA-N 8-chloro-3-methyl-5-pyrrol-1-yl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1N1C=CC=C1 XINWVWPVSCGKJU-UHFFFAOYSA-N 0.000 claims description 2
- YWMDBNUBAGRKLQ-UHFFFAOYSA-N 8-chloro-5-cyclohex-2-en-1-yl-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1CCCC=C1 YWMDBNUBAGRKLQ-UHFFFAOYSA-N 0.000 claims description 2
- LTQIAJAFDWMJTE-UHFFFAOYSA-N 8-chloro-5-cyclohexyl-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1CCCCC1 LTQIAJAFDWMJTE-UHFFFAOYSA-N 0.000 claims description 2
- QTRSQVRJSMUFNF-UHFFFAOYSA-N 8-chloro-5-cyclohexyloxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1OC1CCCCC1 QTRSQVRJSMUFNF-UHFFFAOYSA-N 0.000 claims description 2
- UWJZELKDZCMKAN-UHFFFAOYSA-N 8-chloro-5-ethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound CCOC1CN(C)CCC2=CC(Cl)=C(O)C=C12 UWJZELKDZCMKAN-UHFFFAOYSA-N 0.000 claims description 2
- ZRNUCTXOLFRDOO-UHFFFAOYSA-N 8-chloro-5-ethoxy-n,n,5-trimethyl-1,2,3,4-tetrahydro-3-benzazepine-7-carboxamide Chemical compound CCOC1(C)CNCCC2=CC(Cl)=C(C(=O)N(C)C)C=C12 ZRNUCTXOLFRDOO-UHFFFAOYSA-N 0.000 claims description 2
- VVFBHNJTTAXEPI-UHFFFAOYSA-N 8-chloro-5-ethylsulfanyl-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound CCSC1CN(C)CCC2=CC(Cl)=C(O)C=C12 VVFBHNJTTAXEPI-UHFFFAOYSA-N 0.000 claims description 2
- MPKFCNPYESGCCE-UHFFFAOYSA-N 8-chloro-5-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound COC1CN(C)CCC2=CC(Cl)=C(O)C=C12 MPKFCNPYESGCCE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- SUACDOBINQPHIA-UHFFFAOYSA-N [8-chloro-3-methyl-5-(3-methylbut-2-enyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl] acetate Chemical compound CC(C)=CCC1CN(C)CCC2=CC(Cl)=C(OC(C)=O)C=C21 SUACDOBINQPHIA-UHFFFAOYSA-N 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 230000020335 dealkylation Effects 0.000 claims description 2
- 238000006900 dealkylation reaction Methods 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 238000007031 hydroxymethylation reaction Methods 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- RRHPQRCPGVDEPK-UHFFFAOYSA-N (8-chloro-5-cyclohexyl-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl) ethyl carbonate Chemical compound C1N(C)CCC=2C=C(Cl)C(OC(=O)OCC)=CC=2C1C1CCCCC1 RRHPQRCPGVDEPK-UHFFFAOYSA-N 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 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 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract description 4
- 125000001188 haloalkyl group Chemical group 0.000 abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 abstract description 3
- 125000000304 alkynyl group Chemical group 0.000 abstract description 3
- 208000028017 Psychotic disease Diseases 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 2
- 230000036407 pain Effects 0.000 abstract description 2
- 125000001424 substituent group Chemical group 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000000168 pyrrolyl group Chemical group 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
- 239000000243 solution Substances 0.000 description 58
- 239000000203 mixture Substances 0.000 description 57
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000002904 solvent Substances 0.000 description 17
- 239000000463 material Substances 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 239000007983 Tris buffer Substances 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 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 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000012038 nucleophile Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 6
- 229960005333 tetrabenazine Drugs 0.000 description 6
- 206010015995 Eyelid ptosis Diseases 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 230000001430 anti-depressive effect Effects 0.000 description 5
- 239000000935 antidepressant agent Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000004533 oil dispersion Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 201000003004 ptosis Diseases 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011343 solid material Substances 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 4
- GOTMKOSCLKVOGG-OAHLLOKOSA-N (5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1([C@@H]2C3=CC(O)=C(Cl)C=C3CCN(C2)C)=CC=CC=C1 GOTMKOSCLKVOGG-OAHLLOKOSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000007336 electrophilic substitution reaction Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000003470 muricidal effect Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 3
- 229950001675 spiperone Drugs 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 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
- 230000000202 analgesic effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 230000002508 compound effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 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
- 239000012265 solid product Substances 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
- 239000003381 stabilizer Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 150000003461 sulfonyl halides Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-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
- 239000003981 vehicle Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SCAKFUJVCFIFOX-UHFFFAOYSA-N 1-phenylsulfanylpyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1SC1=CC=CC=C1 SCAKFUJVCFIFOX-UHFFFAOYSA-N 0.000 description 1
- HUMIEJNVCICTPJ-UHFFFAOYSA-N 2,2-dimethoxy-n-methylethanamine Chemical compound CNCC(OC)OC HUMIEJNVCICTPJ-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- MEXPXLPUVFBQGJ-UHFFFAOYSA-N 5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical class C1NCCC2=CC=CC=C2C1C1=CC=CC=C1 MEXPXLPUVFBQGJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 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 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 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
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001090 anti-dopaminergic effect Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- ZJULYDCRWUEPTK-UHFFFAOYSA-N dichloromethyl Chemical compound Cl[CH]Cl ZJULYDCRWUEPTK-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 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
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002143 fast-atom bombardment mass spectrum Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- VIANBEAUACIOKY-UHFFFAOYSA-M sodium;3-ethoxy-3-oxopropanoate Chemical compound [Na+].CCOC(=O)CC([O-])=O VIANBEAUACIOKY-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/32—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3213587A | 1987-03-27 | 1987-03-27 | |
| PCT/US1988/000899 WO1988007526A1 (en) | 1987-03-27 | 1988-03-24 | Substituted benzazepines, their preparation and pharmaceutical compositions containing them |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO885096D0 NO885096D0 (no) | 1988-11-15 |
| NO885096L NO885096L (no) | 1988-11-15 |
| NO174507B true NO174507B (no) | 1994-02-07 |
| NO174507C NO174507C (da) | 1994-05-18 |
Family
ID=21863286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO885096A NO174507B (no) | 1987-03-27 | 1988-11-15 | Analogifremgangsmaate for fremstilling av terapeutisk aktive substiuerte benzazepiner |
Country Status (18)
| Country | Link |
|---|---|
| EP (2) | EP0357641A1 (da) |
| JP (1) | JPH0662574B2 (da) |
| KR (1) | KR930011489B1 (da) |
| AT (1) | ATE112766T1 (da) |
| AU (1) | AU619744B2 (da) |
| CA (1) | CA1321195C (da) |
| DE (1) | DE3851769T2 (da) |
| DK (1) | DK165688C (da) |
| FI (1) | FI894566A0 (da) |
| HU (1) | HU205744B (da) |
| IL (1) | IL85855A (da) |
| MY (1) | MY103357A (da) |
| NO (1) | NO174507B (da) |
| NZ (1) | NZ224038A (da) |
| PH (1) | PH27337A (da) |
| PT (1) | PT87068B (da) |
| WO (1) | WO1988007526A1 (da) |
| ZA (1) | ZA882080B (da) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK107688D0 (da) * | 1988-03-01 | 1988-03-01 | Novo Industri As | Carbaminsyreestere af substituerede 7-hydroxy-2,3,4,5-tetrahydro-1h-3-benzazepiner |
| DK67489D0 (da) * | 1989-02-14 | 1989-02-14 | Novo Industri As | Nye benzazepinderivater |
| US5068326A (en) * | 1989-04-03 | 1991-11-26 | Kung Hank F | Dopamine receptor ligands and imaging agents |
| AU8201591A (en) * | 1990-06-15 | 1992-01-07 | Schering Corporation | 8-lower alkyl-5-cycloalkyl or 5-cycloalkenyl substitued benzazepines and pharmaceutical compositions containing them |
| WO1992005157A1 (en) * | 1990-09-25 | 1992-04-02 | Schering Corporation | Peri-condensed benzazepines |
| US5241065A (en) * | 1992-02-25 | 1993-08-31 | Schering Corporation | 2,3,4,5-tetrahydro-1h-3-benzazepines having anti-psychotic activity |
| ATE305454T1 (de) * | 2000-07-05 | 2005-10-15 | Ortho Mcneil Pharm Inc | Nichtpeptidische substituierte spirobenzoazepine als vasopressin antagonisten |
| US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| CA2509413C (en) * | 2002-12-20 | 2012-05-01 | Glaxo Group Limited | Benzazepine derivatives for the treatment of neurological disorders |
| EP1646623A2 (en) | 2003-05-22 | 2006-04-19 | Schering Corporation | 5-h-benzo[d]naphth[2,1-b]azepine derivative as selective d1/d5 receptor antagonists for the treatment of obesity and cns disorders |
| ES2571220T3 (es) | 2003-06-17 | 2016-05-24 | Arena Pharm Inc | Clorhidrato de 8-cloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzazepina |
| WO2005003096A1 (en) | 2003-06-17 | 2005-01-13 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives useful for the treatment of 5ht2c receptor associated diseases |
| AU2012200805B2 (en) * | 2003-06-17 | 2015-01-22 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives useful for the treatment of 5HT2C receptor associated diseases |
| US20070275949A1 (en) * | 2003-10-22 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2C Receptor Associated Diseases |
| US20080009478A1 (en) * | 2003-10-22 | 2008-01-10 | Arena Pharmaceuticals, Inc. | Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2c Receptor Associated Diseases |
| US8168624B2 (en) | 2004-12-21 | 2012-05-01 | Arena Pharmaceuticals, Inc. | Crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride |
| CN102627607A (zh) | 2004-12-23 | 2012-08-08 | 艾尼纳制药公司 | 5HT2c受体调节剂组合物和使用方法 |
| CA2646044A1 (en) | 2006-04-03 | 2007-10-25 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates related thereto |
| SG177128A1 (en) | 2006-12-05 | 2012-01-30 | Arena Pharm Inc | Processes for preparing (r)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates thereof |
| US8822727B2 (en) | 2008-03-04 | 2014-09-02 | Arena Pharmaceuticals, Inc. | Processes for the preparation of intermediates related to the 5-HT2C agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine |
| US8952197B2 (en) | 2009-06-18 | 2015-02-10 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 5-HT2C receptor agonists |
| WO2011153206A1 (en) | 2010-06-02 | 2011-12-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 5-ht2c receptor agonists |
| WO2012030957A2 (en) | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Non-hygroscopic salts of 5-ht2c agonists |
| MX2013002418A (es) | 2010-09-01 | 2013-08-01 | Arena Pharm Inc | Administracion de lorcaserina a individuos con daño renal. |
| CN103189053A (zh) | 2010-09-01 | 2013-07-03 | 艾尼纳制药公司 | 用于体重控制的5-ht2c激动剂的调节释放剂型 |
| MX2013002422A (es) | 2010-09-01 | 2013-05-17 | Arena Pharm Inc | Sales de lorcaserina con acidos opticamente activos. |
| MY181736A (en) | 2012-10-09 | 2021-01-05 | Arena Pharm Inc | Method of weight management |
| HU230826B1 (hu) | 2014-11-19 | 2018-07-30 | Richter Gedeon Nyrt. | Eljárás benzazepin származékok előállítására |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA974989A (en) * | 1968-03-11 | 1975-09-23 | Wallace And Tiernan Inc. | Process for preparing 1,2,4,5-tetrahydro-3h,3-benzazepines and products obtained thereby |
| DE1934150A1 (de) * | 1968-07-10 | 1970-01-15 | Pennwalt Corp | Neue 1-Alkanoyloxy-1,2,4,5-tetrahydro-3H,3-benzazepine |
| US4988690A (en) * | 1982-06-14 | 1991-01-29 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines and anti-depressant use thereof |
| DK180485D0 (da) * | 1985-04-22 | 1985-04-23 | Novo Industri As | Nitrogenholdige forbindelser |
| US4707483A (en) * | 1985-12-20 | 1987-11-17 | Smithkline Beckman Corporation | 1-phenyl-3-benzazepines and their use for treating gastrointestinal motility disorders |
| GB8807922D0 (en) * | 1988-04-05 | 1988-05-05 | Fujisawa Pharmaceutical Co | Isoquinoline compound & process for preparation thereof |
-
1988
- 1988-03-23 PH PH36675A patent/PH27337A/en unknown
- 1988-03-23 ZA ZA882080A patent/ZA882080B/xx unknown
- 1988-03-24 WO PCT/US1988/000899 patent/WO1988007526A1/en not_active Application Discontinuation
- 1988-03-24 EP EP88903596A patent/EP0357641A1/en active Pending
- 1988-03-24 EP EP88104758A patent/EP0285919B1/en not_active Expired - Lifetime
- 1988-03-24 DE DE3851769T patent/DE3851769T2/de not_active Expired - Fee Related
- 1988-03-24 IL IL85855A patent/IL85855A/xx not_active IP Right Cessation
- 1988-03-24 AT AT88104758T patent/ATE112766T1/de not_active IP Right Cessation
- 1988-03-24 JP JP63503399A patent/JPH0662574B2/ja not_active Expired - Lifetime
- 1988-03-24 AU AU15964/88A patent/AU619744B2/en not_active Ceased
- 1988-03-24 MY MYPI88000305A patent/MY103357A/en unknown
- 1988-03-24 HU HU882812A patent/HU205744B/hu not_active IP Right Cessation
- 1988-03-24 PT PT87068A patent/PT87068B/pt not_active IP Right Cessation
- 1988-03-24 CA CA000562352A patent/CA1321195C/en not_active Expired - Fee Related
- 1988-03-24 KR KR1019880701534A patent/KR930011489B1/ko not_active IP Right Cessation
- 1988-03-25 NZ NZ224038A patent/NZ224038A/xx unknown
- 1988-11-15 NO NO885096A patent/NO174507B/no unknown
- 1988-11-23 DK DK652688A patent/DK165688C/da active
-
1989
- 1989-09-27 FI FI894566A patent/FI894566A0/fi not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ZA882080B (en) | 1989-04-26 |
| DE3851769D1 (de) | 1994-11-17 |
| IL85855A0 (en) | 1988-09-30 |
| DK165688B (da) | 1993-01-04 |
| EP0357641A1 (en) | 1990-03-14 |
| WO1988007526A1 (en) | 1988-10-06 |
| HU205744B (en) | 1992-06-29 |
| ATE112766T1 (de) | 1994-10-15 |
| HUT53882A (en) | 1990-12-28 |
| DK652688A (da) | 1988-11-23 |
| EP0285919A1 (en) | 1988-10-12 |
| MY103357A (en) | 1993-06-30 |
| KR930011489B1 (ko) | 1993-12-08 |
| AU619744B2 (en) | 1992-02-06 |
| FI894566A (fi) | 1989-09-27 |
| FI894566A0 (fi) | 1989-09-27 |
| PH27337A (en) | 1993-06-08 |
| KR890700577A (ko) | 1989-04-25 |
| NO174507C (da) | 1994-05-18 |
| DE3851769T2 (de) | 1995-03-09 |
| EP0285919B1 (en) | 1994-10-12 |
| PT87068B (pt) | 1992-07-31 |
| JPH02502723A (ja) | 1990-08-30 |
| NZ224038A (en) | 1990-10-26 |
| AU1596488A (en) | 1988-11-02 |
| PT87068A (pt) | 1988-04-01 |
| NO885096D0 (no) | 1988-11-15 |
| CA1321195C (en) | 1993-08-10 |
| DK165688C (da) | 1993-05-24 |
| IL85855A (en) | 1993-02-21 |
| JPH0662574B2 (ja) | 1994-08-17 |
| DK652688D0 (da) | 1988-11-23 |
| NO885096L (no) | 1988-11-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO174507B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive substiuerte benzazepiner | |
| US5015639A (en) | Substituted benzazepines, their preparation and pharmaceutical compositions containing them | |
| US5247080A (en) | Substituted benzazepines useful as intermediates for producing pharmaceutically active compounds | |
| US5068234A (en) | 3-arylcarbonyl-1-(c-attached-n-heteryl)-1h-indoles | |
| NO171017B (no) | Analogifremgangsmaate for fremstilling av nye terapeutisk aktive cykliske aminderivater | |
| DE2539452A1 (de) | 1,3,4-trisubstituierte-4-arylpiperidine | |
| HU190902B (en) | Process for preparing 1-aryl-oxy-2,3,4,5-tetrahydro-3-benzazepine derivatives and acid addition salts thereof | |
| US5498610A (en) | Neuroprotective indolone and related derivatives | |
| CA1333485C (en) | Fused benzazepines | |
| WO1991019698A1 (en) | 8-lower alkyl-5-cycloalkyl or 5-cycloalkenyl substitued benzazepines and pharmaceutical compositions containing them | |
| US4973586A (en) | Fused benzazepines, compositions of, and medical use thereof | |
| Sauerberg et al. | Cyclic carbamate analogs of pilocarpine | |
| EP0175525B1 (en) | 7-[2-(Dialkylamino)ethyl]-4-hydroxy-1,3-benzimidazol-2-ones | |
| EP0513174B1 (en) | 4,5-cycloalkano-3-benzazepin-7-ol-derivatives and their use | |
| EP0233049A1 (en) | 2,3,4,8,9,9a-Hexahydro-4-aryl-1H-indeno[1,7-cd]azepines | |
| JPH09501954A (ja) | イミダゾ［５，１−ｃ］［１，４］ベンゾキサジン−１−オンのイミダゾリルアルキル誘導体およびそれらの製造法 | |
| US5302716A (en) | Fused benzazepines | |
| US5440033A (en) | Indolyl-, pyrrolyl- and pyrazolyl substituted benzazepines | |
| NO177264B (no) | Analogifremgangsmåte for fremstilling av terapeutisk aktive, kondenserte benzazepiner, samt forbindelser for anvendelse som mellomprodukter ved analogifremgangsmåten | |
| NO851423L (no) | Benzazepinderivater, farmasoeytiske preparater inneholdende disse og fremgangsmaater for fremstilling av slike forbindelser og preparater | |
| US5374722A (en) | Bridged benzazepines | |
| HU208117B (en) | Process for producing new substituted 1-akrylsulfonyl-2-pyrrolidinones and pharmaceutical compositions comprising such compounds |