Pharmacophore Model Generation of P2Y12 Inhibitor

摘要

A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-platelet aggregation activities targeting platelet adp receptor (P2Y12). 24 structrurally diverse molecules were selected as training set to generate the hypothesis using Catalyst software 4.11. The best hypothesis comprises one hydrogen-bond acceptor, one aromatic ring, three hydrophobic points and one excluded volume and shows high correlation coefficient (0.999) as well as low RMS deviation (1.24). It has been further validated towards a test set and shows high correlation coefficient of test set (0.978). The values of effectively active hit A% and comprehensive evaluation index CAI are respectively 40% and 2.795. The results show that the pharmacophore we built is reliable and can be used to screen database. Furthermore, the best hypothesis was used to screen TCMD (Version 2005) database and the four hit compounds of higher predicted activity were the reported anti-platelet aggregation inhibitions, which may be useful for further study.