Searching for Novel Lead Compounds of α1-AR Antagonists: Synthesis, Bioassays and 3D-QSAR of 2-[4-(Aryloxyalkyl)-piperazin-1-yl]benzo[d]oxazole Compounds

Abstract

Abstract:

Benign prostatic hyperplasia(BPH) is a pathological disorder in the aged men that causes voiding difficulties and thus impacts the quality of life. α₁-AR antagonists are clinically used for the treatment of BPH. Aimed at searching for the novel α₁-adrenoceptor antagonists, eight target compounds bearing 2-(piperazin-1-yl)benzo[d]oxazole scaffold were designed from our lead compound wb5c and synthesized from 5-chloro-2-aminophenol and substituted phenols via condensation, chloration and amination, Williamson ether synthesis and substitution etc.. All target compounds were identified by ESI-MS, IR, ¹H NMR and HRMS. Functional bioassays showed that they had moderate antagonistic activities against α₁-AR. The CoMFA model was constructed for 2-(piperazin-1-yl)benzo[d]oxazole derivertives via SYBYL software package, q²=0.430, r²=0.907, fractions of steric and electrostatic fields were 0.465 and 0.535, respectively. 3D-QSAR analysis leads to insight into further structural optimization.

Key words: Benign prostatic hyperplasia(BPH), α1-Adrenoceptor, Antagonists, Benzoxazole, Piperazine, CoMFA model

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LI Jia-Bin, LIU Hai-Chun, ZHANG Li, WANG Tao, JIANG Zhen-Zhou3, XIA Lin*. Searching for Novel Lead Compounds of α₁-AR Antagonists: Synthesis, Bioassays and 3D-QSAR of 2-[4-(Aryloxyalkyl)-piperazin-1-yl]benzo[d]oxazole Compounds[J]. Chem. J. Chinese Universities, 2009, 30(5): 903.

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Searching for Novel Lead Compounds of α₁-AR Antagonists: Synthesis, Bioassays and 3D-QSAR of 2-[4-(Aryloxyalkyl)-piperazin-1-yl]benzo[d]oxazole Compounds

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