Studies on histaminergic compounds VIII. A new series of compounds showing H1-antagonistic and H2-agonistic properties; synthesis, in vitro pharmacology and structure—activity relationships

To study the structure—activity relationships (SAR) of impromidine-like H₂-agonists, we prepared some analogues of the potent agonist VUF 8405 (an analogue of impromidine in which the 5-methylimidazole moiety was replaced by a phenyl group) by replacing the benzyl group of VUF 8405 with substituted diphenylmethyl moieties and a number of related groups. The compounds have been tested for H₁-activity on guinea pig ileum and trachea. To determine the H₂-activity, the compounds have been investigated on both the right atrium and gastric fundus of the guinea pig. The SAR for H₁-antagonistic activity of this series of compounds on the ileum was found to be analogous to that on the trachea. A significant difference was found between the H₂-SAR on the right atrium and gastric fundus.Because of this combination of H₁-antagonism and H₂-agonism, some of these compounds might be clinically useful, for instance in the treatment of certain allergic disturbances and some kinds of heart failure.