[Synthesis and combined H1-/H2 antagonist activity of mepyramine, pheniramine and cyclizine derivatives with cyanoguanidine, urea and nitroethenediamine partial structures].
Compounds with combined histamine H1- and H2-receptor antagonist activity were synthesized by connecting H1- and H2-receptor substructures via cyanoguanidine, urea, or nitroethenediamine moieties. Loss of the strongly basic side-chain nitrogen results in a decrease of H1-receptor activity compared to single reference compounds. At the guinea-pig right atrium (H2-receptor model) compounds with mepyramine or cyclizine structure are also less active than the single references tiotidine, ranitidine, or lamtidine. Nevertheless substances with a pheniramine like partial structure proved to be potent histamine H2-receptor antagonists at the atrium model (about 27 times more active than cimetidine).
Schulze
F R
FR
Institut für Pharmazie, Freie Universität Berlin.
Alisch
R A
RA
Buschauer
A
A
Schunack
W
W
D000818:Animals; D003501:Cyclizine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D005029:Ethylenediamines / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010632:Pheniramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D011738:Pyrilamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D014508:Urea / Q000737:chemistry
D005029:Ethylenediamines; D006146:Guanidines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010632:Pheniramine; D014508:Urea; D011738:Pyrilamine; C004711:dicyandiamido; D003501:Cyclizine
Synthese und kombinierte H1-/H2-antagonistische Aktivität von Mepyramin-, Pheniramin- und Cyclizin-Derivaten mit Cyanoguanidin-, Harnstoff- und Nitroethendiamin-Partialstrukturen.