Potential histamine H2-receptor blockers. 3- and 2-indole derivatives as immobile analogues of tautomeric forms of cimetidine.
At physiological pH, cimetidine (1a) and its analogues burimamide (1b) and metiamide (1c) exist mainly as an equilibrium mixture of tautomers. A high concentration of tautomer 2 is associated with increased H2-receptor interaction. 3-Indole derivatives (5c-f) and 2-indole derivatives (6c-f) were synthesized and tested as immobile analogues of tautomers 2 and 3, respectively. Weak competitive H2 antagonism was found in N'-cyano-N-[2-[(1H-indol-3-ylmethyl)thio]ethyl]carbamidothioic acid methyl ester (5e) and N-[2-[(1H-indol-2-ylmethyl)thio]-ethyl]-N'-methylthiourea (6c).
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002927:Cimetidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006146:Guanidines; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D013237:Stereoisomerism
D006146:Guanidines; D006635:Histamine H2 Antagonists; D007211:Indoles; D008761:Methylhistamines; C025566:4-methylhistamine; D002927:Cimetidine