ON THE ROLE OF THE MOLECULAR ELECTROSTATIC POTENTIAL IN MODELING THE ACTIVITY OF NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS

Continuing our theoretical studies of the non-peptide angiotensin II r eceptor antagonists, we performed a comparative analysis of the molecu lar electrostatic potential (MEP) distributions of several Du Pont inh ibitors. 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 init io and semiempirical wavefunctions were compared to verify the possibi lity of obtaining reliable values with less computational effort. On t he 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 represen tation techniques were used: maps in meaningful planes, and surfaces c orresponding to a given value of potential. Significant electrostatic dissimilarities between active and inactive compounds were detected, e specially in the overall topology of the long-range negative MEP distr ibution around the C2 side-chain.