3D QSAR analysis of novel 5-HT1A receptor ligands

In an effort to develop a quantitative ligand-binding model for 5-HT1A rece ptors, a pharmacophore mapping procedure, DIStance COmparison (DISCO) was u sed to identify structural features that are common in a novel set of pyrid azinothiazepines and pyridazinooxazepines with moderate-to-high affinity to 5-HT1A-receptors. The pharmacophore thus obtained provided a good starting point for a Comparative Molecular Field Analysis (CoMFA) study. The CoMFA gave acceptable statistical measure (R-CV(2) = 0.52 by using six latent var iables, whereas it afforded a noncross-validated R-2 value of 1.00). Predic tability of our model was tested by a separated prediction set of four comp ounds, for them the relative deviations between calculated and measured bio logical activity values did not exceed 10%. (C) 1999 Elsevier Science B.V. All rights reserved.