1-(2-pyridinyl)piperazine derivatives with antianaphylactic, antibronchospastic, and mast cell stabilizing activities.
New 1-(2-pyridinyl)piperazine derivatives were synthesized and tested as inhibitors of the reaginic passive cutaneous anaphylaxis in the rat (PCA), of the histamine-induced bronchospasm in the guinea pig, and of the rat mesenteric mast cell degranulation induced by compound 48/80. On the basis of test results, a series of N-(substituted phenyl)-omega-[4-(2-pyridinyl)-1-piperazinyl]alkanamides was prepared. The nature of substituents at the anilide ring strongly influenced mast cell stabilizing activity, whereas it was less determining in the case of the other two tests. No clear correlation between the most common physicochemical parameters (pi, sigma, Vw volume) of substituents and activity could be detected. With regard to the position of substituents at the anilide ring, the rank order of potency, in the PCA and bronchoconstriction tests, was para greater than meta greater than ortho. Introduction of substituents in the 1-(2-pyridinyl)piperazinyl moiety of the N-(substituted phenyl)propanamide derivatives hardly affected activity, or the effect was deleterious. Some of the new compounds exhibited a simultaneous remarkable activity in all the three assays employed.
D000818:Animals; D001986:Bronchial Spasm / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D006801:Humans; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D010879:Piperazines; D011725:Pyridines; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine