title: Receptor-based QSAR study for a series of 3,3-disubstituted-5-aryl oxindoles and 6-aryl benzimidazol-2-ones derivatives as progesterone receptor inhibitors.
abstract: Receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 54 progesterone receptor (PR) inhibitors. The established CoMFA model from the training set gives statistically significant results with the cross-validated q (2) of 0.534 and non-cross-validated [Formula: see text] of 0.947. The best CoMSIA model was derived by the combination of steric field and hydrophobic field with a q (2) of 0.615 and [Formula: see text] of 0.954. A test set of 18 compounds was used to validate the predictive ability of the two models. The predicted correlation coefficients [Formula: see text] are 0.681 and 0.677 for CoMFA and CoMSIA models, respectively. Based on the CoMFA maps, the key structural characters of progesterone receptor inhibitors are identified. Moreover, the binding modes of oxindoles and benzimidazol-2-ones are also given by the quantum mechanical/molecular mechanical (QM/MM) calculations. This may provide useful information for drug design.
authors: Key Lab of Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, China.
authors: J H
authors: JH
authors: Wang
authors: Q Q
authors: QQ
authors: Hou
authors: K
authors: K
authors: Tang
authors: X L
authors: XL
authors: Cheng
authors: L H
authors: LH
authors: Dong
authors: Y J
authors: YJ
authors: Liu
authors: C B
authors: CB
authors: Liu
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008962:Models, Theoretical; D015394:Molecular Structure; D000078183:Oxindoles; D021281:Quantitative Structure-Activity Relationship; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*
chemical_list: D001562:Benzimidazoles; D007211:Indoles; D000078183:Oxindoles; D011980:Receptors, Progesterone; C022960:2-oxindole; C053110:benzimidazol-2-one