Synthesis,biological evaluation and 3D-QSAR study of 1-(1,4-benzodioxan-2-ylcaronyl)-4-aryloxyalkyl-piperazines as α₁-adrenoceptor antagonists

In order to search for new α₁-adrenoceptor antagonists bearing 1,4-benzodioxane moiety,six new target compounds ( 7a-7f ) were synthesized from catechol via ring-closing,hydrolysis,amidation，substitution and salt formation. Their structures were confirmed by ESI-MS, ¹H NMR，IR and HR-MS. Preliminary biological evaluation result showed that most of the target compounds had modest blocking activity against α₁-adrenoceptor and the pA₂ value of 7e was greater than 7.00. 3D-QSAR study of the title compounds was performed via Sybyl software. Based on our previous work，CoMFA model was constructed from eighteen 1-(1,4-benzodioxan-2-ylcaronyl)- 4-aryloxy-alkyl-piperazine analogues (q²=0.753,r²=0.986)，and these results would be helpful for further structural optimization of 1,4-benzodioxane α₁-adrenoceptor antagonists.