Pharmacophore model of integrin α_vβ₃ antagonists

In order to generate a pharmacophore model of integrin α_vβ₃ receptor antagonists and design lead compounds which have potent and selective activity against α_vβ₃ receptor with the help of this model.  Thirty compounds (four categories) with highly inhibitory activity against the integrin α_vβ₃ 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 α_vβ₃ receptor antagonists with the Catalyst software.  The best pharmacophore model of integrin α_vβ₃ 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 α_vβ₃ receptor were designed with the new pharmacophore models.