[Studies on zwitter-ionization of drugs. I. 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 H1 in several tissues.
Muramatsu
H
H
First Division of the Research Laboratory for Development of Medicine, Hokuriku University, Ishikawa, Japan.
Sawanishi
H
H
Iwasaki
N
N
Kakiuchi
M
M
Ohashi
T
T
Kato
H
H
Ito
Y
Y
D000657:Amoxapine / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D003984:Dibenzazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010879:Piperazines; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D013841:Thiazepines / Q000138:chemical synthesis / Q000494:pharmacology*
D003984:Dibenzazepines; D010879:Piperazines; D012702:Serotonin Antagonists; D013841:Thiazepines; C077986:4-(11H-dibenz(b,e)azepin-6-yl)piperazine; C077985:4-(2-chlorodibenzo(bf)(1,4)thiazepin-11-yl)piperazine; D000657:Amoxapine; D009638:Norepinephrine