Searching for the Novel Lead Compounds of α1-AR Antagonists (Part I): Design, Synthesis and Bioassay of 5-Chloro-2-[4-(aryloxyalkyl)piperazin-1-yl] benzo[d]oxazole Compounds
LI, Jia-Bin a JIANG, Zhen-Zhou b WANG, Tao b LIU, Ming-Ming a XIA, Jun c WU, Bin d XIA, Lin *,e
(a Department of Inorganic Chemistry, China Pharmaceutical University, Nanjing 210009) (b National Drug Screening Center, China Pharmaceutical University, Nanjing 210009) (c New Drug Research Center, China Pharmaceutical University, Nanjing 210009) (d Department of Medicinal Chemistry, Nanjing Medical Univeristy, Nanjing 210029) (e Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009)
To search for the new α1-adrenoceptor antagonists, 11 target compounds bearing a 2-(piperazin-1-yl) benzo[d]oxazole scaffold were designed from our lead compound 2-[(4-(2-(2-chloropheno- xy)-ethyl)-piperazin-1-yl)methyl]-5-methylbenzo[d]oxazole (wb5c) and synthesized from 5-chloro-2- aminophenol and substituted phenols via condensation, chloration, amination, Williamson ether synthesis and substitution etc. All the target compounds were identified by ESI-MS, IR, 1H NMR and HRMS. Functional bioassay showed that they had moderate antagonistic activities against α1-AR, which verified our three-element pharmacophore model. In conclusion, 5-chloro-2-(4-(aryloxyalkyl)piperazin-1-yl)benzo- [d]oxazole compounds were novel candidates as potential α1-AR antagonist.