title: [Pharmacophore model of integrin alphavbeta3 antagonists].
abstract: In order to generate a pharmacophore model of integrin alphavbeta3 receptor antagonists and design lead compounds which have potent and selective activity against alphavbeta3 receptor with the help of this model. Thirty compounds (four categories) with highly inhibitory activity against the integrin alphavbeta3 receptor (IC50 < 110 nmol x L(-1)), amide, piperazine, piperidine, gamma-valerolactam as the intermediate junction, separately, were selected as a training set to construct a three-dimensional pharmacophore models of integrin alphavbeta3 receptor antagonists with the Catalyst software. The best pharmacophore model of integrin alphavbeta3 receptor antagonists with RMS = 0.73, Correl = 0.90, Weight = 1.17, Config = 14.00 is found out, which consisting of four features: a neg ionizable core (NI), two aliphatic hydrophobic core (HP) and an aromatic ring center (RA). Some new and easily obtained compounds with fine ADME properties and highly potent activity against alphavbeta3 receptor were designed with the new pharmacophore models.
authors: Department of Medicinal Chemistry, School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Gang-ying
authors: GY
authors: Cheng
authors: Guang-hui
authors: GH
authors: Ni
authors: Feng-chao
authors: FC
authors: Jiang
mesh_terms: D017076:Computer-Aided Design; D015195:Drug Design; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D039302:Integrin alphaVbeta3