STUDIES ON ZWITTER-IONIZATION OF DRUGS .1. SYNTHESIS AND PHARMACOLOGICAL ACTIVITIES OF N-ALKYLCARBOXYLIC ACID-DERIVATIVES OF 4-(2-CHLORODIBENZ[B,F][1,4]OXAZEPIN-11-YL)PIPERAZINE, 4-(2-CHLORODIBENZO[B,F][1,4]THIAZEPIN-11-YL)PIPERAZINE, AND 4-(11H-DIBENZ[B,E]AZEPIN-6-YL)PIPERAZINE

The piperazine N-alkylcarboxylic acids of 2-chlorodibenz[b,f] [1,4] oxazepine (3a), 2-chlorodibenzo[b,f] [1,4] thiazepine (3b), and dipenz[b,e]azepine (3c) from the corresponding piperazines (1a-c, R1 = H) were synthesized via the piperazine N-alkylcarboxylates (2a-c). The pharmacological activities of the piperazine N-alkylcarboxylic acids (3a-c) were evaluated. Compared with the parent compounds (1a-c), 3a-c (n=1-5) showed weak inhibitory activities on the uptake of noradrenaline and 5-hydroxytryptamine (5-HT) into hypothalamus vesicles and moderate antagonistic actions to 5-HT2 and H-1, in several tissues.