[Impromidine-analogous guanidines: synthesis and activity at the histamine H2-receptor. 29. Histamine analogs].
19 impromidine analogous guanidines were synthetized by acid hydrolysis of the corresponding N-cyanoguanidines. The guanidines were tested on the isolated spontaneously beating guinea-pig atrium for histamine H2-receptor affinity. Lengthening the ethyl chain of cysteamine by one methylene group leads to partial agonists of decreased activity. Impromidine congeners containing a branched cimetidine side chain prove to be potent H2-agonists with maximal or near maximal response. Affinity ratios in favour of the (R)-configurated enantiomers are moderate but clearly significant. The interaction between the affinity contributing moiety and the complementary receptor area shows a lower degree of stereoselectivity than does the efficacy contributing (imidazole-4-yl)propyl substituent of impromidine and sopromidine, respectively. Homoisohistamine derivatives dramatically lose both efficacy and affinity.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D017446:Impromidine; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D006146:Guanidines; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011970:Receptors, Histamine H2; D017446:Impromidine
Impromidin-analoge Guanidine: Synthese und Wirkung am Histamin-H2-Rezeptor. 29. Mitteilung: Histamin-Analoga.