THEORETICAL-STUDIES APPLICABLE TO THE DESIGN OF NOVEL ANTICONVULSANTS.2. A COMPARISON OF AM1, MNDO, AND PM3 SEMIEMPIRICAL MOLECULAR-ORBITAL CONFORMATIONAL-ANALYSES OF DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKERS

The optimization of the anticonvulsant activity of dihydropyridine cal cium channel blockers (DHPs) requires suitable structure-activity stud ies, which in turn require reliable methods of conformational analysis . The utility of AM1, MNDO, and PM3 as methods of conformational analy sis for the DHPs was critically assessed. Eighteen DHPs were fully opt imized using AM1, MNDO, and PM3, and the results were compared with cr ystal geometries. AM1 was best suited to the modelling of DHP geometri es, based on root mean square fit analysis and the treatment of specif ic functional groups. The performance of the three techniques was rela ted to the corrective term of the core repulsion function of the semie mpirical hamiltonians.