QSARS WITH ORTHOGONAL DESCRIPTORS ON PSYCHOTOMIMETIC PHENYLALKYLAMINES

Multiple linear regressions have been obtained for 49 psychotomimetic phenylalkylamines. The MTD method has been applied and the MTD paramet er was used as steric descriptor. The energy of the lowest unoccupied molecular orbital and the net charges on the phenyl ring atoms (from A M1 calculations) have been used as electronic descriptors and logP(ow) , or average electrostatic field as lipophilicity descriptor. Hall and Kier electrotopological state indices were also tested. The descripto rs have been scaled to unit and orthogonalized by Randic method. The p redictability of the regressions obtained from MTD method have been ch ecked by a method similar to cross-validation from CoMFA method. MTD h as been identified as the dominant descriptor by Randic orthogonalizat ion. The best model has been obtained with MTD and electrotopological state indices, showing the importance of the steric and electronic pro perties for the interaction at the receptor site level.