DE2633679A1 - 4,5-dihydro-2-niederalkoxycarbonylamino-4-phenylimidazole und derivate davon mit substituierter phenylgruppe - Google Patents
4,5-dihydro-2-niederalkoxycarbonylamino-4-phenylimidazole und derivate davon mit substituierter phenylgruppeInfo
- Publication number
- DE2633679A1 DE2633679A1 DE19762633679 DE2633679A DE2633679A1 DE 2633679 A1 DE2633679 A1 DE 2633679A1 DE 19762633679 DE19762633679 DE 19762633679 DE 2633679 A DE2633679 A DE 2633679A DE 2633679 A1 DE2633679 A1 DE 2633679A1
- Authority
- DE
- Germany
- Prior art keywords
- dihydro
- pharmaceutically acceptable
- compound according
- namely
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 PHENYL GROUP Chemical group 0.000 title claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 173
- 239000000203 mixture Substances 0.000 claims description 95
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 92
- 150000003839 salts Chemical class 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 82
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
- 239000011737 fluorine Substances 0.000 claims description 24
- 229910052731 fluorine Inorganic materials 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052740 iodine Inorganic materials 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 12
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 239000011630 iodine Substances 0.000 claims description 11
- 239000012458 free base Substances 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 claims description 5
- SBUKTYMKOFPXBT-UHFFFAOYSA-N methyl n-(5-phenyl-4,5-dihydro-1h-imidazol-2-yl)carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC=C1 SBUKTYMKOFPXBT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- OKHQWADIIMWOOX-UHFFFAOYSA-N ethyl n-(5-phenyl-4,5-dihydro-1h-imidazol-2-yl)carbamate Chemical compound C1NC(NC(=O)OCC)=NC1C1=CC=CC=C1 OKHQWADIIMWOOX-UHFFFAOYSA-N 0.000 claims description 2
- WDBCIKBJISOGJW-UHFFFAOYSA-N methyl n-[5-(2,5-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(F)=CC=C1F WDBCIKBJISOGJW-UHFFFAOYSA-N 0.000 claims description 2
- ZLDOJTHEEJPHCD-UHFFFAOYSA-N methyl n-[5-(4-ethylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1=CC(CC)=CC=C1C1N=C(NC(=O)OC)NC1 ZLDOJTHEEJPHCD-UHFFFAOYSA-N 0.000 claims description 2
- CCCMYBZGMWPGAX-UHFFFAOYSA-N methyl n-[5-(4-hydroxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=C(O)C=C1 CCCMYBZGMWPGAX-UHFFFAOYSA-N 0.000 claims description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 10
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
- 241000272517 Anseriformes Species 0.000 claims 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
- 150000005215 alkyl ethers Chemical class 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims 1
- ZPESCLUTTFJXPZ-UHFFFAOYSA-N methyl n-[5-(2,3-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(F)=C1F ZPESCLUTTFJXPZ-UHFFFAOYSA-N 0.000 claims 1
- STOJHLLUMXHQOY-UHFFFAOYSA-N methyl n-[5-(2,6-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound N1C(NC(=O)OC)=NCC1C1=C(F)C=CC=C1F STOJHLLUMXHQOY-UHFFFAOYSA-N 0.000 claims 1
- WKFHCBPNWQSRAN-UHFFFAOYSA-N methyl n-[5-(2-bromophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC=C1Br WKFHCBPNWQSRAN-UHFFFAOYSA-N 0.000 claims 1
- LRXOSVQHYWVZRI-UHFFFAOYSA-N methyl n-[5-(2-iodophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC=C1I LRXOSVQHYWVZRI-UHFFFAOYSA-N 0.000 claims 1
- OYCGJUPVHCQMLQ-UHFFFAOYSA-N methyl n-[5-(3,4-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=C(F)C(F)=C1 OYCGJUPVHCQMLQ-UHFFFAOYSA-N 0.000 claims 1
- COJIWGFZGMBLRV-UHFFFAOYSA-N methyl n-[5-(3-methoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(OC)=C1 COJIWGFZGMBLRV-UHFFFAOYSA-N 0.000 claims 1
- OLLVZDTWVNJNSN-UHFFFAOYSA-N methyl n-[5-(3-methylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(C)=C1 OLLVZDTWVNJNSN-UHFFFAOYSA-N 0.000 claims 1
- QXXCSFQQXIZWFF-UHFFFAOYSA-N methyl n-[5-(4-ethoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1=CC(OCC)=CC=C1C1N=C(NC(=O)OC)NC1 QXXCSFQQXIZWFF-UHFFFAOYSA-N 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 53
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 52
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 239000007858 starting material Substances 0.000 description 32
- 230000000694 effects Effects 0.000 description 31
- 230000008018 melting Effects 0.000 description 31
- 238000002844 melting Methods 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 24
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 19
- 229960004592 isopropanol Drugs 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 206010010904 Convulsion Diseases 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 11
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 229960003147 reserpine Drugs 0.000 description 11
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 150000003949 imides Chemical class 0.000 description 9
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 239000000935 antidepressant agent Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 230000001430 anti-depressive effect Effects 0.000 description 7
- 239000001961 anticonvulsive agent Substances 0.000 description 7
- 229940005513 antidepressants Drugs 0.000 description 7
- 230000000994 depressogenic effect Effects 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229940125725 tranquilizer Drugs 0.000 description 6
- 239000003204 tranquilizing agent Substances 0.000 description 6
- 230000002936 tranquilizing effect Effects 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- 230000001773 anti-convulsant effect Effects 0.000 description 5
- 210000002027 skeletal muscle Anatomy 0.000 description 5
- 208000007101 Muscle Cramp Diseases 0.000 description 4
- 208000005392 Spasm Diseases 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- 229960003965 antiepileptics Drugs 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000036461 convulsion Effects 0.000 description 4
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002631 hypothermal effect Effects 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 150000002823 nitrates Chemical class 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010021118 Hypotonia Diseases 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
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229940125681 anticonvulsant agent Drugs 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- 150000003935 benzaldehydes Chemical class 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 125000004212 difluorophenyl group Chemical group 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- KHBXLYPOXVQKJG-UHFFFAOYSA-N methyl n-[(methoxycarbonylamino)-methylsulfanylmethylidene]carbamate Chemical compound COC(=O)NC(SC)=NC(=O)OC KHBXLYPOXVQKJG-UHFFFAOYSA-N 0.000 description 3
- 230000036640 muscle relaxation Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000004089 psychotropic agent Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
- 230000001256 tonic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CRVBQABBEKLFIN-UHFFFAOYSA-N 1-phenylethane-1,2-diamine Chemical compound NCC(N)C1=CC=CC=C1 CRVBQABBEKLFIN-UHFFFAOYSA-N 0.000 description 2
- ZVHIGOVJILOQNV-UHFFFAOYSA-N 1-phenylethane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NCC(N)C1=CC=CC=C1 ZVHIGOVJILOQNV-UHFFFAOYSA-N 0.000 description 2
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
- YMLGFOQFNCEGMG-UHFFFAOYSA-N 5-phenyl-4,5-dihydro-1h-imidazol-2-amine;hydrobromide Chemical compound Br.C1NC(N)=NC1C1=CC=CC=C1 YMLGFOQFNCEGMG-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- AZIIOYYYBHUUQM-UHFFFAOYSA-N COCNC(SC)=NCOC Chemical compound COCNC(SC)=NCOC AZIIOYYYBHUUQM-UHFFFAOYSA-N 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- 206010015995 Eyelid ptosis Diseases 0.000 description 2
- 208000008238 Muscle Spasticity Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 208000001936 exophthalmos Diseases 0.000 description 2
- 210000001105 femoral artery Anatomy 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 239000011147 inorganic material Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 description 2
- VRKIIVUHLLPVPU-UHFFFAOYSA-N methyl n-[5-(2,3-dichlorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(Cl)=C1Cl VRKIIVUHLLPVPU-UHFFFAOYSA-N 0.000 description 2
- BUAVHLIXPKWMEQ-UHFFFAOYSA-N methyl n-[5-(2,5-dichlorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(Cl)=CC=C1Cl BUAVHLIXPKWMEQ-UHFFFAOYSA-N 0.000 description 2
- LJTJBIYLDAEOHC-UHFFFAOYSA-N methyl n-[5-(2,6-dichlorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound N1C(NC(=O)OC)=NCC1C1=C(Cl)C=CC=C1Cl LJTJBIYLDAEOHC-UHFFFAOYSA-N 0.000 description 2
- LCJLJYCKZURRJT-UHFFFAOYSA-N methyl n-[5-(2-ethylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCC1=CC=CC=C1C1N=C(NC(=O)OC)NC1 LCJLJYCKZURRJT-UHFFFAOYSA-N 0.000 description 2
- NACPWUMSPVYYFT-UHFFFAOYSA-N methyl n-[5-(3-fluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound N1C(NC(=O)OC)=NCC1C1=CC=CC(F)=C1 NACPWUMSPVYYFT-UHFFFAOYSA-N 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
- 229940001470 psychoactive drug Drugs 0.000 description 2
- 230000000506 psychotropic effect Effects 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- JWDYCNIAQWPBHD-UHFFFAOYSA-N 1-(2-methylphenyl)glycerol Chemical compound CC1=CC=CC=C1OCC(O)CO JWDYCNIAQWPBHD-UHFFFAOYSA-N 0.000 description 1
- PPNCOQHHSGMKGI-UHFFFAOYSA-N 1-cyclononyldiazonane Chemical compound C1CCCCCCCC1N1NCCCCCCC1 PPNCOQHHSGMKGI-UHFFFAOYSA-N 0.000 description 1
- BJXUCBAQZJITKD-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carbaldehyde Chemical compound O1CCOC2=C1C=CC=C2C=O BJXUCBAQZJITKD-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
- PWVUXRBUUYZMKM-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCO PWVUXRBUUYZMKM-UHFFFAOYSA-N 0.000 description 1
- WJBMRZAHTUFBGE-UHFFFAOYSA-N 2-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC(CCN)=C1 WJBMRZAHTUFBGE-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- RWLVSRXXLIFXEG-UHFFFAOYSA-N 2-methylpropyl n-(5-phenyl-4,5-dihydro-1h-imidazol-2-yl)carbamate Chemical compound C1NC(NC(=O)OCC(C)C)=NC1C1=CC=CC=C1 RWLVSRXXLIFXEG-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- QRZMXADUXZADTF-UHFFFAOYSA-N 4-aminoimidazole Chemical compound NC1=CNC=N1 QRZMXADUXZADTF-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- MVXMNHYVCLMLDD-UHFFFAOYSA-N 4-methoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=C2C(OC)=CC=C(C=O)C2=C1 MVXMNHYVCLMLDD-UHFFFAOYSA-N 0.000 description 1
- XHLKOHSAWQPOFO-UHFFFAOYSA-N 5-phenyl-1h-imidazole Chemical compound N1C=NC=C1C1=CC=CC=C1 XHLKOHSAWQPOFO-UHFFFAOYSA-N 0.000 description 1
- BHUSOIQBDQNPAZ-UHFFFAOYSA-N 5-phenyl-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1NC(N)=NC1C1=CC=CC=C1 BHUSOIQBDQNPAZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 150000000994 L-ascorbates Chemical class 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
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000010476 Respiratory Paralysis Diseases 0.000 description 1
- 240000002114 Satureja hortensis Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- QZPSXPBJTPJTSZ-UHFFFAOYSA-N aqua regia Chemical compound Cl.O[N+]([O-])=O QZPSXPBJTPJTSZ-UHFFFAOYSA-N 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 238000009739 binding Methods 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004188 dichlorophenyl group Chemical class 0.000 description 1
- 229940031768 diglycol stearate Drugs 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000003104 endogenous depression Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- VSSYAALYQWYTMN-UHFFFAOYSA-N ethyl N-[5-(3,4-dihydroxyphenyl)-4,5-dihydro-1H-imidazol-2-yl]carbamate Chemical compound CCOC(=O)NC=1NC(CN=1)C1=CC(=C(C=C1)O)O VSSYAALYQWYTMN-UHFFFAOYSA-N 0.000 description 1
- NMHBKSHIKGHTFR-UHFFFAOYSA-N ethyl n-(1h-imidazol-2-yl)carbamate Chemical compound CCOC(=O)NC1=NC=CN1 NMHBKSHIKGHTFR-UHFFFAOYSA-N 0.000 description 1
- VXIAUFYTTKFKOI-UHFFFAOYSA-N ethyl n-[5-(2,6-dimethoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OCC)=NC1C1=C(OC)C=CC=C1OC VXIAUFYTTKFKOI-UHFFFAOYSA-N 0.000 description 1
- OHWNRGFVSIPSOL-UHFFFAOYSA-N ethyl n-[5-(4-propan-2-ylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OCC)=NC1C1=CC=C(C(C)C)C=C1 OHWNRGFVSIPSOL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 229940047127 fiore Drugs 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
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- XLNLLSGSCHZCBJ-UHFFFAOYSA-N hexyl (nz)-n-[(hexoxycarbonylamino)-methylsulfanylmethylidene]carbamate Chemical compound CCCCCCOC(=O)NC(SC)=NC(=O)OCCCCCC XLNLLSGSCHZCBJ-UHFFFAOYSA-N 0.000 description 1
- UGPITOGWBQNGPU-UHFFFAOYSA-N hexyl n-(5-phenyl-1h-imidazol-2-yl)carbamate Chemical compound N1C(NC(=O)OCCCCCC)=NC(C=2C=CC=CC=2)=C1 UGPITOGWBQNGPU-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 150000002462 imidazolines Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229960003861 mephenesin Drugs 0.000 description 1
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- IUEBEACSGQRJBB-UHFFFAOYSA-N methyl n-(1h-imidazol-2-yl)carbamate Chemical compound COC(=O)NC1=NC=CN1 IUEBEACSGQRJBB-UHFFFAOYSA-N 0.000 description 1
- YTRMMDLFEDZUMJ-UHFFFAOYSA-N methyl n-[5-(2,3-dimethylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(C)=C1C YTRMMDLFEDZUMJ-UHFFFAOYSA-N 0.000 description 1
- AWQSSQDQQJWXAF-UHFFFAOYSA-N methyl n-[5-(2,4-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=C(F)C=C1F AWQSSQDQQJWXAF-UHFFFAOYSA-N 0.000 description 1
- SNZAFCBMTRXYKB-UHFFFAOYSA-N methyl n-[5-(2,5-dibromophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(Br)=CC=C1Br SNZAFCBMTRXYKB-UHFFFAOYSA-N 0.000 description 1
- GXJDFSBDCDXQKG-UHFFFAOYSA-N methyl n-[5-(2,5-dimethoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(OC)=CC=C1OC GXJDFSBDCDXQKG-UHFFFAOYSA-N 0.000 description 1
- XIINOCXUFYAACI-UHFFFAOYSA-N methyl n-[5-(2,5-dimethylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(C)=CC=C1C XIINOCXUFYAACI-UHFFFAOYSA-N 0.000 description 1
- FOEBGTBETWQAQU-UHFFFAOYSA-N methyl n-[5-(2,6-dibromophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=C(Br)C=CC=C1Br FOEBGTBETWQAQU-UHFFFAOYSA-N 0.000 description 1
- IOMUXKWBKOYEED-UHFFFAOYSA-N methyl n-[5-(2,6-diethoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCOC1=CC=CC(OCC)=C1C1N=C(NC(=O)OC)NC1 IOMUXKWBKOYEED-UHFFFAOYSA-N 0.000 description 1
- BOBZIDOLEXHAAH-UHFFFAOYSA-N methyl n-[5-(2-butoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCCCOC1=CC=CC=C1C1N=C(NC(=O)OC)NC1 BOBZIDOLEXHAAH-UHFFFAOYSA-N 0.000 description 1
- LKQNTDMZVXADOZ-UHFFFAOYSA-N methyl n-[5-(2-fluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound N1C(NC(=O)OC)=NCC1C1=CC=CC=C1F LKQNTDMZVXADOZ-UHFFFAOYSA-N 0.000 description 1
- KKAGJZBREFIUNM-UHFFFAOYSA-N methyl n-[5-(2-hexylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCCCCCC1=CC=CC=C1C1N=C(NC(=O)OC)NC1 KKAGJZBREFIUNM-UHFFFAOYSA-N 0.000 description 1
- UEAZHXZPNBDPJP-UHFFFAOYSA-N methyl n-[5-(2-methoxyphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC=C1OC UEAZHXZPNBDPJP-UHFFFAOYSA-N 0.000 description 1
- SCENJXMYGONCSK-UHFFFAOYSA-N methyl n-[5-(2-methylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC=C1C SCENJXMYGONCSK-UHFFFAOYSA-N 0.000 description 1
- GNIZQSUJWQKUDE-UHFFFAOYSA-N methyl n-[5-(3,5-difluorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(F)=CC(F)=C1 GNIZQSUJWQKUDE-UHFFFAOYSA-N 0.000 description 1
- VSVIVUXYMBXJQT-UHFFFAOYSA-N methyl n-[5-(3,5-ditert-butylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 VSVIVUXYMBXJQT-UHFFFAOYSA-N 0.000 description 1
- LUPZGMPBLXFXEZ-UHFFFAOYSA-N methyl n-[5-(3-chlorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(Cl)=C1 LUPZGMPBLXFXEZ-UHFFFAOYSA-N 0.000 description 1
- QAKSHROSRKXJLU-UHFFFAOYSA-N methyl n-[5-(3-ethylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCC1=CC=CC(C2N=C(NC(=O)OC)NC2)=C1 QAKSHROSRKXJLU-UHFFFAOYSA-N 0.000 description 1
- FLWLDYAOSULAMK-UHFFFAOYSA-N methyl n-[5-(3-hexylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound CCCCCCC1=CC=CC(C2N=C(NC(=O)OC)NC2)=C1 FLWLDYAOSULAMK-UHFFFAOYSA-N 0.000 description 1
- KPLTVMAZMSYGGH-UHFFFAOYSA-N methyl n-[5-(4-chlorophenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=C(Cl)C=C1 KPLTVMAZMSYGGH-UHFFFAOYSA-N 0.000 description 1
- UEXSJZQANZASTC-UHFFFAOYSA-N methyl n-[5-(4-hexylphenyl)-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1=CC(CCCCCC)=CC=C1C1N=C(NC(=O)OC)NC1 UEXSJZQANZASTC-UHFFFAOYSA-N 0.000 description 1
- POYRIRJPWKDFSU-UHFFFAOYSA-N methyl n-[5-[3-(trifluoromethyl)phenyl]-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=CC(C(F)(F)F)=C1 POYRIRJPWKDFSU-UHFFFAOYSA-N 0.000 description 1
- AEIOMGZZGNTXGA-UHFFFAOYSA-N methyl n-[5-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1h-imidazol-2-yl]carbamate Chemical compound C1NC(NC(=O)OC)=NC1C1=CC=C(C(F)(F)F)C=C1 AEIOMGZZGNTXGA-UHFFFAOYSA-N 0.000 description 1
- MMBDAJMDNVQFDV-UHFFFAOYSA-N methyl n-[amino(methylsulfanyl)methylidene]carbamate Chemical compound COC(=O)N=C(N)SC MMBDAJMDNVQFDV-UHFFFAOYSA-N 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- RACWCHHOBPMSHO-UHFFFAOYSA-N n-benzyl-1-phenylethane-1,2-diamine Chemical compound C=1C=CC=CC=1C(CN)NCC1=CC=CC=C1 RACWCHHOBPMSHO-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LFLZOWIFJOBEPN-UHFFFAOYSA-N nitrate, nitrate Chemical compound O[N+]([O-])=O.O[N+]([O-])=O LFLZOWIFJOBEPN-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229960002511 phenobarbital sodium Drugs 0.000 description 1
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229940125706 skeletal muscle relaxant agent Drugs 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/20—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 hydrogenated in the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59969475A | 1975-07-28 | 1975-07-28 | |
| US59955175A | 1975-07-28 | 1975-07-28 | |
| US68268276A | 1976-05-03 | 1976-05-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2633679A1 true DE2633679A1 (de) | 1977-02-17 |
Family
ID=27416783
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19762633679 Pending DE2633679A1 (de) | 1975-07-28 | 1976-07-27 | 4,5-dihydro-2-niederalkoxycarbonylamino-4-phenylimidazole und derivate davon mit substituierter phenylgruppe |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US4080335A (enExample) |
| AT (1) | AT353263B (enExample) |
| AU (1) | AU504595B2 (enExample) |
| BE (1) | BE844515A (enExample) |
| CA (1) | CA1070697A (enExample) |
| DE (1) | DE2633679A1 (enExample) |
| FR (1) | FR2319349A1 (enExample) |
| GB (1) | GB1519689A (enExample) |
| NL (1) | NL7608383A (enExample) |
| SE (1) | SE7608479L (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001500A1 (en) * | 1977-10-07 | 1979-04-18 | Syntex (U.S.A.) Inc. | 1-Carbocyclic aryl-2-mono or -bis(alkoxycarbonyl) guanidino ethanes, and methods for their preparation and the preparation therefrom of 4,5-dihydro-2-alkoxycarbonylamino-5-carbocyclic aryl imidazoles |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4088771A (en) * | 1976-07-26 | 1978-05-09 | Syntex (U.S.A.) Inc. | 1-Lower alkyl-4,5-dihydro-5-phenyl-2-lower alkoxy carbonylaminoimidazoles and substituted phenyl derivatives thereof |
| US4110463A (en) * | 1977-06-03 | 1978-08-29 | Syntex (U.S.A.) Inc. | Imidazole-2-carbamates |
| US4198422A (en) * | 1979-05-17 | 1980-04-15 | E. R. Squibb & Sons, Inc. | Substituted 2,3-naphthimidazole carbamates and method |
| US4294844A (en) * | 1979-06-04 | 1981-10-13 | Syntex (U.S.A.) Inc. | Use of 4,5-dihydro-2-lower alkoxycarbonylamino-4-phenyl imidazoles and substituted phenyl derivatives thereof as anti-hypertensive agents |
| YU204680A (en) * | 1979-08-31 | 1983-10-31 | Syntex Inc | Process for obtaining 4-phenyl-and 5-phenyl-1,4,5,6-tetrahydro pyrimidine derivatives |
| US4322421A (en) * | 1979-08-31 | 1982-03-30 | Syntex (U.S.A.) Inc. | 4-Phenyl-and 5-phenyl-1,4,5,6-tetrahydro-pyrimidine derivatives |
| US4261995A (en) * | 1979-08-31 | 1981-04-14 | Syntex (U.S.A.) Inc. | 4-Phenyl-and 5-phenyl-1,4,5,6-tetrahydropyrimidine derivatives |
| US4329459A (en) * | 1980-05-05 | 1982-05-11 | The Upjohn Company | Tetrahydrobenzopyran derivatives |
| US4999356A (en) * | 1987-08-07 | 1991-03-12 | Hoechst-Roussel Pharmaceuticals, Inc. | 1-phenyl-3-(1-piperazinyl)-1H-indazoles |
| FR2639227A1 (fr) * | 1988-11-23 | 1990-05-25 | Sanofi Sa | Utilisation de derives du chromane pour le traitement des etats depressifs |
| EP2343145A1 (en) * | 2003-03-05 | 2011-07-13 | Mitsubishi Materials Corporation | Throw-away tipped drill, throw-away tip, and drill main body |
| AU2007208127A1 (en) * | 2006-01-25 | 2007-08-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| US9196844B2 (en) * | 2012-06-01 | 2015-11-24 | Semiconductor Energy Laboratory Co., Ltd. | Method of synthesizing pyrazine derivative, and light-emitting element, light-emitting device, electronic device, and lighting device |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1357633A (en) * | 1971-03-02 | 1974-06-26 | Beecham Group Ltd | Chromanone basic ether derivatives |
-
1976
- 1976-01-26 US US05/652,041 patent/US4080335A/en not_active Expired - Lifetime
- 1976-07-23 CA CA257,631A patent/CA1070697A/en not_active Expired
- 1976-07-26 AU AU16221/76A patent/AU504595B2/en not_active Expired
- 1976-07-26 BE BE169237A patent/BE844515A/xx unknown
- 1976-07-26 FR FR7622762A patent/FR2319349A1/fr active Granted
- 1976-07-27 DE DE19762633679 patent/DE2633679A1/de active Pending
- 1976-07-27 SE SE7608479A patent/SE7608479L/xx unknown
- 1976-07-28 NL NL7608383A patent/NL7608383A/xx not_active Application Discontinuation
- 1976-07-28 AT AT554876A patent/AT353263B/de not_active IP Right Cessation
- 1976-07-28 GB GB30915/76A patent/GB1519689A/en not_active Expired
-
1977
- 1977-10-17 US US05/842,655 patent/US4129661A/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001500A1 (en) * | 1977-10-07 | 1979-04-18 | Syntex (U.S.A.) Inc. | 1-Carbocyclic aryl-2-mono or -bis(alkoxycarbonyl) guanidino ethanes, and methods for their preparation and the preparation therefrom of 4,5-dihydro-2-alkoxycarbonylamino-5-carbocyclic aryl imidazoles |
Also Published As
| Publication number | Publication date |
|---|---|
| US4129661A (en) | 1978-12-12 |
| FR2319349B1 (enExample) | 1979-07-13 |
| CA1070697A (en) | 1980-01-29 |
| GB1519689A (en) | 1978-08-02 |
| BE844515A (fr) | 1977-01-26 |
| AU1622176A (en) | 1978-02-02 |
| AU504595B2 (en) | 1979-10-18 |
| ATA554876A (de) | 1979-04-15 |
| US4080335A (en) | 1978-03-21 |
| NL7608383A (nl) | 1977-02-01 |
| AT353263B (de) | 1979-11-12 |
| FR2319349A1 (fr) | 1977-02-25 |
| SE7608479L (sv) | 1977-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2711451C2 (enExample) | ||
| DE69804273T2 (de) | 5h-Thiazolo[3,2-a]pyrimidinderivate | |
| CH616676A5 (enExample) | ||
| DE2952279A1 (de) | Neue 2-acylaminomethyl-1,4-benzodiazepine und deren salze sowie verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE2633679A1 (de) | 4,5-dihydro-2-niederalkoxycarbonylamino-4-phenylimidazole und derivate davon mit substituierter phenylgruppe | |
| DE2220906A1 (de) | Neue substituierte 2-phenylaminoimidazoline-(2), deren saeureadditionssalze sowie verfahren zu deren herstellung | |
| EP1071670A1 (de) | Diphenyl-substituierte 5-ring-heterocyclen, verfahren zu ihrer herstellung sowie deren verwendung als arzneimittel | |
| EP0104423A1 (de) | 2-Nitro-1,1-ethendiamine, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel | |
| EP0621037B1 (de) | Pyrido-pyrimidindione, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
| DE1670305C3 (de) | 5-Phenyl-2,4-dioxo-1,2,3,4-tetrahydro-3H-1,5-benzodiazepine und Verfahren zu ihrer Herstellung | |
| DE2362754C2 (de) | Cyclopropylalkylaminoreste enthaltende Oxazolinverbindungen, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE3309655A1 (de) | 1,2,5-thiadiazol-1-oxide und 1,1-dioxide, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel | |
| DE3900028A1 (de) | Gegebenenfalls am phenylrest halogen- und/oder alkyl- und/oder alkoxy- oder methylendioxysubstituierte, 5,5-di-(methyl)-3-(phenylvinyl)-1-(substituiert amino-alkoxy-imino)-cyclohex-2-enderivate, verfahren zu ihrer herstellung sowie diese enthaltende arzneimittel | |
| DE2713933C2 (enExample) | ||
| DE2733698A1 (de) | 1-niederalkyl-4,5-dihydro-5-phenyl- 2-niederalkoxycarbonylaminoimidazole und deren im phenylrest substituierte derivate | |
| DE2550959C3 (de) | Tetrazolyl-imidazole und Tetrazolyl--benzimidazole, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel | |
| DE3112984A1 (de) | 2-(3-(4-(3-chlor-4-fluorphenyl)-1-piperazinyl) propyl)-1,2,4-triazolo(4,3-a)pyridin-3(2h)-on dessen pharmazeutische anwendung und herstellung | |
| DE2518032A1 (de) | 2-aminoimidazole, verfahren zu deren herstellung und dieselben enthaltendes mittel | |
| EP0004529B1 (de) | Tantomere Arylaminoimidazolinderivate, deren Herstellung und sie enthaltende Arzneimittel zur Bekämpfung von Schmerzzuständen | |
| DE2240256A1 (de) | Imidazoline und verfahren zu deren herstellung | |
| EP0054839A2 (de) | 2-Acylaminomethyl-1,4-benzodiazepine und deren Salze sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| EP0280290B1 (de) | Mittel mit antidepressiver Wirkung | |
| DE3012190A1 (de) | Pharmazeutisches mittel auf der basis 1,3,5-substituierter biuret-verbindungen | |
| DE2650231A1 (de) | Neue imidazolverbindungen, verfahren zu ihrer herstellung und diese enthaltende arzneimittel | |
| DE3404193A1 (de) | 5-fluor-pyrimidin-2-yl-piperazin-verbindung, verfahren zu ihrer herstellung und pharmazeutische mittel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHN | Withdrawal |