Contributions of Crystal Structures, Molecular Electrostatic Potential Maps, and Lipophilicity Data to Structure-Activity Relationships of some Conformationally Restricted Nortropane Benzamide Neuroleptics

Structural, electronic, and lipophilicity characteristics of dihydro-2,3-methoxy-4 and dihydro-2,3[(phenylmethyl)-8 aza-8 bicyclo[3.2.1.] octyl-3]-2 1H-isoindolone-1, (exo), two conformationally restricted nortropane benzamide derivatives (subgroup of neuroleptic drugs) have been determined and compared to other more “flexible” analogs in order to explain their pharmacological antidopaminergic D2 activities. Molecular structures of both compounds were obtained using single crystal X-ray crystallography; molecular electrostatic potential maps were computed at theab initio MO STO-3G level, and the capacity factors were measured by RP-HPLC.