On the role of the molecular electrostatic potential in modelling the activity of non peptide angiotensin II receptor antagonists

Continuing our theoretical studies of the non-peptide angiotensin II receptor antagonists, we performed a comparative analysis of the molecular electrostatic potential (MEP) distributions of several Du Pont inhibitors. On the basis of previous results we extensively analysed the potential generated by the molecular fragment including the imidazolic ring and the side-chain at the 2-position. MEPs obtained from ab initio and semiempirical wavefunctions were compared to verify the possibility of obtaining reliable values with less computational effort. On the basis of this analysis we chose to compute ab initio the MEP of all the examined molecular fragments with a 3-21G basis set. Two representation techniques were used: maps in meaningful planes, and surfaces corresponding to a given value of potential. Significant electrostatic dissimilarities between active and inactive compounds were detected, especially in the overall topology of the long-range negative MEP distribution around the C2 side-chain