Structure-Activity Correlations for Psychotomimetics. III. Tryptamines

Abstract

Based on electronic properties calculated by the semiempirical PM3 method, a quantitative structure-activity relationship has been derived for a group of psychotomimetic tryptamines. Data analysis by partial least squares reveals two significant components. The major property affecting potency was the difference in energy between the highest occupied and lowest unoccupied molecular orbital. Less significant was the effect of molecular size, shape and polarizability, in particular, the dimension in the direction of the ethylamine side chain, involving the substituents on the amine nitrogen. The results are consistent with earlier studies on phenylalkylamines.