Constructing Biophore of Uroselective α1-Adrenoceptor antagonist

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Constructing Biophore of Uroselective α1-Adrenoceptor antagonist

FANG Hao, LU Jing-fen^*, XIA Lin

1.State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China;
2.Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

Received:2003-04-21 Revised:2003-11-10 Online:2003-12-15 Published:2003-12-15
Contact: LU Jing-fen*

Abstract

Abstract: 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 antagonists (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 building the biophore. Using an automatic filtering software for obtaining reasonable biophores, the filter parameters were se-lected: P (probability)>0.8, active (number of active compounds)≥4, and size (descriptor center)≥3. Results Three biophores 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 de-veloped by computer simulation with Apex-3D software can be used to design and synthesize a new α1-adrenoceptor antago-nist with high activity and low side effect.

Key words: α1-adrenoceptor antagonist, α1-adrenoceptor antagonist, uroselectivity, uroselectivity, Apex-3D, Apex-3D, biophore, biophore

CLC Number:

R916.1

916.67

Supporting:

FANG Hao, LU Jing-fen^*, XIA Lin . Constructing Biophore of Uroselective α1-Adrenoceptor antagonist[J]. .

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