In an effort to develop a quantitative ligand-binding model for 5- HT(1A) 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-HT(1A)-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 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%.
ASJC Scopus subject areas
- Analytical Chemistry
- Process Chemistry and Technology
- Computer Science Applications