QSARs with Orthogonal Descriptors on Psychotomimetic Phenylalkylamines

Abstract

AbstractMultiple linear regressions have been obtained for 49 psychotomimetic phenylalkylamines. The MTD method has been applied and the MTD parameter was used as steric descriptor. The energy of the lowest unoccupied molecular orbital and the net charges on the phenyl ring atoms (from AMI calculations) have been used as electronic descriptors and logPow, or average electrostatic field as lipophilicity descriptor. Hall and Kier electrotopological state indices were also tested. The descriptors have been scaled to unit and orthogonalized by Randic method. The predictability of the regressions obtained from MTD method have been checked by a method similar to cross‐validation from CoMFA method. MTD has been identified as the dominant descriptor by Randic orthogonalization. The best model has been obtained with MTD and electrotopological state indices, showing the importance of the steric and electronic properties for the interaction at the receptor site level.