Pharmacophore model of integrin α_vβ_3 antagonists

In order to generate a pharmacophore model of integrin αvβ3 receptor antagonists and design lead compounds which have potent and selective activity against αvβ3 receptor with the help of this model. Thirty compounds (four categories) with highly inhibitory activity against the integrin αvβ3 receptor (IC50 110 nmol·L-1), amide, piperazine, piperidine, γ-valerolactam as the intermediate junction, separately, were selected as a training set to construct a three-dimensional pharmacophore models of integrin αvβ3 receptor antagonists with the Catalyst software. The best pharmacophore model of integrin αvβ3 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 αvβ3 receptor were designed with the new pharmacophore models.