Constructing Biophore of Uroselective α1-Adrenoceptor antagonist
摘要
Aim The biophore of uroselective α1-adrenoceptor antagonist was studied by using Apex-3D software on an O2 Silicon Graphics Computer Station. Methods Five known antagonism (Indoramin, GG-818, RS100975, R-YM12167,and KMD-3213), which possess both good selectivity and high affinities to prostate and α1-AR subtype, were chosen for htilding the biophore. Using an autoraatic filtering software for obtaining reasonable biophorcs, the filter parameters were selected: P (probability) >0.8, active (number of active compounds)≥4, and size (descriptor center)≥3. Results Three biophorcs conformed to the requirements, each of whom contained a basic center, an aromatic ring center and H-site according to the structure-activity relationships of known α1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulation with Apex-3D software can be used to design and synthesize a new α1-adrenoeeptor antagonist with high activity and low side effect.