1-(1,4-苯并二噁烷-2-羰基)-4-取代芳氧烷基哌嗪类α1受体拮抗剂的合成、生物活性及3D-QSAR研究  

Synthesis,biological evaluation and 3D-QSAR study of 1-(1,4-benzodioxan-2-ylcaronyl)-4-aryloxyalkyl-piperazines as α_1-adrenoceptor antagonists

作　　者：李嘉宾[1] 宣文胜[2] 牛菊[2] 江振洲[3] 王涛[3] 夏霖[4] 

机构地区：[1]中国药科大学无机化学教研室,南京210009 [2]巢湖市第二人民医院药剂科,巢湖238000 [3]中国药科大学新药筛选中心,南京210009 [4]中国药科大学药物化学教研室,南京210009

出　　处：《中国药科大学学报》2010年第6期499-504,共6页Journal of China Pharmaceutical University

摘　　要：为寻找新的1,4-苯并二噁烷类α1受体拮抗剂,选取1,4-苯并二噁烷为母核,以儿茶酚和取代苯酚为原料,分别经关环、水解、成酰胺、取代、成盐等反应合成了6个新的目标化合物(7a-7f),结构已通过ESI-MS、1HNMR、IR及HR-MS确证。初步药理活性实验结果表明,受试化合物具有中等强度的α1-肾上腺素受体拮抗活性,其中目标化合物7epA2值大于7.00,有进一步研究的价值。运用Sybyl软件对本类化合物开展了3D-QSAR研究,结合本课题组前期工作,构建了1-(1,4-苯并二噁烷-2-羰基)-4-取代芳氧烷基哌嗪类化合物的CoMFA模型,q2=0.753,r2=0.986,为该类α1受体拮抗剂进一步的结构优化提供了理论依据。In order to search for new α_1-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 α_1-adrenoceptor and the pA_2 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 α_1-adrenoceptor antagonists.

关 键 词：良性前列腺增生 Α1受体拮抗剂 1 4-苯并二噁烷 合成 比较分子力场分析 三维定量构效关系 

分 类 号：TQ460.31[化学工程—制药化工] R916.2[医药卫生—药学]