An investigation of the minimal requirements for H 2-receptor agonists: a computational study of N-(3-aminopropyl)formamidine tautomerism

Abstract

A possible role for amidine groups in H 2-receptor agonists is explored in the context of a previously proposed model. In the model, activation of the H 2-receptor by histamine results from a shift in proton tautomeric preference of the two imidazole ring nitrogen atoms induced by the neutralization of the side chain ammonium group. The minimal requirements for activation by the proposed model are satisfied when the imidazole group of histamine is replaced by an amidine group. Thus, the amidine group could play the role of the imidazole group in an H 2-receptor agonist. However, because the amidine nitrogen atoms are more basic than the aliphatic amine nitrogen atom, N-(3-aminopropyl)formamidine itself is not expected to be an H 2-receptor agonist.