QSAR analysis of 2-Acylamino-4, 6-Diphenylpyridine Derivatives as Novel antagonists of GPR-54

GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor plays an essential role to modulate sex-hormones including GnRH. Antagonists of GPR54 (2-acylamino-4, 6-diphenylpyridine derivatives) are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis. The QSAR study on 2-acylamino-4, 6-diphenylpyridine derivatives as novel antagonists of GPR54 was carried out with 30 (21 training + 9 test) compounds. Molecular modeling was performed using ChemOffice 2006; supplied by Cambridge software,USA. The structures drawn were subjected to energy minimization by MM 2 and MOPAC and the lowest energy structure was used to calculate the physiochemical properties. The regression analysis was carried out using an automatic computer program called VALSTAT. The best models were selected from the various statistically significantequations. The analysis resulted in QSAR equation shows that biological activity is positively correlated to LogP (hydrophobicityconstant), Partition Coefficient and Esb (stretch-bend energy). The statistical results of best model are, n=17, r=0.968213, r2 =0.937436, r2 adj=0.922999, q2= 0.849, variance= 0.0678879, Std=0.260553 this study can help in rational drug design and synthesis of new novel GPR54 antagonists with predetermined affinity.