SYNTHESIS AND HISTAMINE H-1-RECEPTOR ANTAGONIST ACTIVITY OF 4-(DIPHENYLMETHYL)-1-PIPERAZINE DERIVATIVES WITH A TERMINAL HETEROARYL OR CYCLOALKYL AMIDE FRAGMENT

New 4-(diphenylmethyl)-1-piperazine derivatives with a terminal hetero aryl or cycloalkyl amide fragment were synthesized and evaluated for t heir antihistaminic, anticholinergic and antiallergic activities. Test ed compounds were found to be moderate to potent in vitro (guinea-pig ileum) histamine H-1-receptor antagonists. Derivatives with a four met hylene chain (1e-1h) were as potent in vivo (capillary permeability in rats) as cetirizine; the heteroaryl derivatives 1e and 1h were found to be the most active agents. These compounds displayed only weak in v itro (guinea-pig ileum) muscarinic M(3)-receptor antagonist activity. Compounds le and Ig were about 100 times more potent than ketotifen in preventing the compound 48/80-induced histamine release from rat peri toneal mast cells. Derivatives 1e, 1f and 1h did not modify the sponta neous motor activity in rats at 100 mg/kg po. Compound 1e has been sel ected for further studies.