Pharmacophore alignments

Figure 20.2 Pharmacophore models for P-gp inhibition. A. P-gp inhibition pharmacophore aligned with the potent inhibitor LY335979. B. P-gp substrate pharmacophore aligned with verapamil. C. P-gp inhibition pharmacophore 2 aligned with LY335979. Green indicates H-bond acceptor feature, and cyan indicates hydrophobic feature. See color plate.

Pharmacophore definition description of the type of pharmacophore locations and associated functions. Can other descriptors be added to the pharmacophore alignment ... 

This is inferred from better correlations (r2 and r( v values) and increased sensitivity associated with a reduction of principal components (PCs). Hence the rj v value yielded for the pharmacophore alignment (PA) drops from 0.63 (five PCs)... 

Zhu LL, Hou TJ, Chen LR, Xu XJ. 3D QSAR analyses of novel tyrosine kinase inhibitors based on pharmacophore alignment. J Chem Inf Comput Sci 2001 41 1032-1040. 

The cannabinoid ligand can be classified according to Ooms et al [43] into six groups i) classical, ii) nonclassical, iii) bicyclic, iv) aminoalkylindoles, v) endocannabinoid analogues, vi) diarylpyrazoles. Ooms et al [43] studied the pharmacophore of 3-alkyl-5-arylimidazolidinediones as a new CBi cannabinoid receptor. Thomas et al [44] have studied SAR data on a series of 1,5-diphenylpyrazoles proposing a pharmacophoric alignment of these compounds with THC... 

Taminau, J., Thijs, G., and De Winter, H. (2008) Pharao pharmacophore alignment and optimization. Journal of Molecular Graphics and Modelling, 27, 161-169. 

Ligand- and structure-based approaches are valuable tools for the identification and optimization of lead compounds. Each strategy needs special prerequisites and has strengths and weaknesses. In some cases only the strengths of both methods may be combined for a joint approach, called structure-based pharmacophore alignment. Here, the receptor site serves as a complement to build the pharmacophore model and sophisticated statistical methods from 3D-QSAR (PCA and PLS) are applied for the prediction of activity [19, 20]. 

---