ABSTRACT
The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1,2-a][1,4]-benzodiazepin-1-one (10) led to the synthesis of a group of compounds with potent minor tranquillizer activity.
Subject(s)
Anti-Anxiety Agents/chemical synthesis , Benzodiazepinones/chemical synthesis , Aggression/drug effects , Animals , Anti-Anxiety Agents/toxicity , Anticonvulsants/chemical synthesis , Benzodiazepinones/pharmacology , Benzodiazepinones/toxicity , Chlorprothixene/pharmacology , Drug Synergism , Electroshock , Hexobarbital/pharmacology , Humans , Male , Mice , Motor Activity/drug effects , Pentylenetetrazole/antagonists & inhibitors , Strychnine/antagonists & inhibitorsABSTRACT
A number of derivatives of 2-methyl-3-(o-tolyl)-4(3H)-quinazolone bearing new substituents on the 2-methyl group have been synthesized. It was established that most substitutions at this position reduce or remove the CNS depressant activity of methaqualone. From the series prepared only the 2-fluoromethyl derivative or certain isothiouronium salts, which could be hydrolyzed in vivo to the 2-mercaptomethyl derivative, showed activity of the same magnitude as methaqualone.
