Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: Synthesis and structure-activity relationships of a new series of H1 antihistamines

Article abstract of DOI:10.1021/jm00129a026

A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H₁ antihistaminic acitivy was synthesized, and the SARs were evaluated. The antihistamine activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H₁ antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4-oxazeN pine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H₁ antihistamine.