[Synthesis and h2-antihistaminic activity of n,n'-bisimidazole-substituted thioureas, cyanoguanidines and 2-nitro-1,1-ethenediamines 10. C: H2-antihistaminics].
In studies on structure-activity relationships of histamine H2-receptor antagonists, N,N'-bis(2-[(4-imidazolyl)-methylthio]-ethyl)-substituted thioureas, cyanoguinidines, and 2-nitro-1,1-ethenediamines with different C-5 methylation of the imidazole rings were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium and the stimulated gastric acid secretion of the anaesthetized rat. When tested on isolated guinea-pig atrium, substances with both C-5 positions methylated (5b, 7b, 9b) proved to be up to seven times more active than metiamide, whereas inhibition of gastric acid secretion turned out to be less marked. While equally methylated thioureas and cyanoguanidines showed same potency, the 2-nitro-1,1-ethenediamines clearly possessed lower activity.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003959:Diamines / Q000138:chemical synthesis / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D019791:Guanidine; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
D003959:Diamines; D006146:Guanidines; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D013890:Thiourea; D019791:Guanidine
Synthese und H2-antihistaminische Wirkung N,N'-bisimidazol-substituierter Thioharnstoffe, Cyanoguanidine und 2-Nitro-1,1-ethendiamine. 10. Mitteilung: H2-Antihistaminika).