SAR studies on H-2 antagonists containing alkylamino substituted 1,2,5-thiadiazole 1-oxide moieties

A number of ranitidine analogues in which the diamino-1,2,5-thiadiazole 1-o xide substructure bearing alkyl chains of different length is present as th e urea equivalent group, were synthesised and studied for their lipophilic and H-2 antagonist properties. Derivatives which displayed a logP less than or equal to 3 behaved as competitive antagonists of histamine at H-2 recep tors present on guinea pig right atrium. The remaining more lipophilic memb ers of the series showed an insurmountable antagonism not completely revers ible after prolonged washing. A binding study suggested that an increase in the length of alkyl chain gave rise to hydrophobic interactions with the r eceptor which were responsible for the apparent irreversible Hz antagonism shown by the higher homologues of the series. (C) 1998 Elsevier Science S.A . All rights reserved.