3D QSAR analysis of novel 5-HT1A receptor ligands

In an effort to develop a quantitative ligand-binding model for 5-HT1A receptors, a pharmacophore mapping procedure, DIStance COmparison (DISCO) was used to identify structural features that are common in a novel set of pyridazinothiazepines 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 (RCV2=0.52 by using six latent variables, whereas it afforded a noncross-validated R2 value of 1.00). Predictability of our model was tested by a separated prediction set of four compounds, for them the relative deviations between calculated and measured biological activity values did not exceed 10%.