title: Potential histamine H2-receptor blockers. 3- and 2-indole derivatives as immobile analogues of tautomeric forms of cimetidine.
abstract: 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).
mesh_terms: 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
chemical_list: D006146:Guanidines; D006635:Histamine H2 Antagonists; D007211:Indoles; D008761:Methylhistamines; C025566:4-methylhistamine; D002927:Cimetidine