Comparative SCF MO studies for some histamine analogues as agonists of the H2 receptor of histamine

Abstract

This paper presents SCF AM1 and CNDO/2 RF calculations of the potential energy surface of histamine monocation (HA) and the agonists 2-(4-thiazolyl)ethylamine (TIA) and 2-(4-oxazolyl)ethylamine (OXA). the similarity of the conformational and electronic structures between HA, TIA and OXA, suggests that both HA analogues should have agonist character, according to the intramolecular proton transfer model that we have proposed in order to explain the activation of the histamine H2 receptor. In this model both the intramolecular proton transfer and the basicity of the nitrogen atoms in the hydrogen bridge are assumed to trigger the activity of the receptor. In this context, the activity of the species analyzed here should decrease in the order HA, TIA and OXA.