Three-dimensional quantitative structure-activity relationships of hallucinogenic phenylalkanamine and tryptamine derivatives: Studies using comparative molecular field analysis (CoMFA)

Investigations of the quantitative structure-activity relationships of a data set comprising 66 phenylalkanamines have been carried out using the CoMFA method. This yielded a cross-validated correlation coefficient (q(2) value) of more than 0.8. The target parameter used was the hallucinogenic effect on humans, since this variable is of particular importance for research into addictive substances. It was possible to confirm the reliability of the CoMFA analysis by using a second, independent phenylalkanamine data set. It was found that models with good predictive properties are obtained if up to ten components are taken into account. In a further step it was possible to include hallucinogenic tryptamine derivatives in a common QSAR analysis with the phenylalkanamines and this in spite of their differing basic structures. The final model from that the CoMFA plots were extracted is based on 148 compounds and permits precise inferences to be made concerning the relationships between structural elements and hallucinogenic effects.