2-(E)-取代苯亚甲基-6-取代胺甲基-1-取代苯基环己醇类化合物的合成及抗炎镇痛、抗癌活性研究  

Synthesis and antitumor,anti inflammatory and analgesic activities of (E) -2-(un)substituted benzylidene -6- ((alkylamino)methyl)-1-aryl cyclohexanols

作　　者：王静丽[1] 赵临襄[1] 郭刚[1] 赵柯军[1] 计志忠[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2004年第6期321-325,353,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (30 1710 99) ;辽宁省自然科学基金项目 (2 0 0 2 10 5 2 )

摘　　要：目的设计合成 2 (E) 取代苯亚甲基 6 取代胺甲基 1 取代苯基环己醇类化合物 (未见文献报道 ) ,并对其抗炎镇痛、抗癌活性进行初步的评价。方法以环己酮为起始原料 ,通过Claisen Schmidt缩合反应、Mannich反应、Grignard反应制得目标产物 ;采用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定该类化合物的抗炎及镇痛活性 ;采用MTT检测法 ,测定目标化合物对HCT 15细胞的生长抑制作用。结果目标化合物结构经红外光谱、核磁共振氢谱及质谱确证。初步药理筛选结果表明 :部分化合物具有显著的抗炎及镇痛活性 ;大部分化合物对HCT 15瘤株具有很强的生长抑制作用。结论合成了 14个未见文献报道的新化合物 ;化合物Ⅲ9、Ⅲ12 及Ⅲ13 的抗炎活性优于对照药布洛芬 ,Ⅲ4的抗炎及镇痛活性均强于对照药布洛芬 ;大部分化合物在 10 μg/mL时 ,对HCT 15瘤株的生长抑制率高于 6 0 % ,其中Ⅲ9的抑制率达到 86 3% ,值得进一步研究。Aim To design and synthesize the novel (E) 2 (un)substituted benzylidene 6 ((alkylamino)methyl) 1 aryl cyclohexanols and assay their antitumor,anti inflammatory and analgesic activities.Methods Using cyclohexanone as the starting material,the target compounds were synthesized through a three step processe,including Claisen Schmidt,Mannich and Grignard reactions.Their growth inhibition to HCT 15 cells were tested by the MTT assay;their anti inflammatory and analgesic activities were evaluated respectively with the model of xylene induced ear edema in mice and acetic acid inducing mice′s writhing.Results The chemical structures of these target compounds were confirmed by IR, 1H NMR and MS.The preliminary pharmacological tests showed that most compounds displayed significant growth inhibition on HCT 15 cells;some compounds showed remarkably anti inflammatory and/or analgesic activities in mice.Conclusion Fourteen unreported compounds were synthesized.The anti inflammatory activities of compounds Ⅲ 9,Ⅲ 12 and Ⅲ 13 were more potent than that of ibuprofen.The compound is comparable to ibuprofen both in anti inflammatory and analgesic activities.The growth inhibition of most compounds at 10 μg/mL on HCT 15 cells is above 60%,and especially that of Ⅲ 9 is 86.3%,and is worthy of further investigation.

关 键 词：药物化学 制备 化学合成 2-(E)-取代苯亚甲基-6-取代胺甲基-1-取代苯基环己醇 抗癌 抗炎 镇痛 

分 类 号：R914[医药卫生—药物化学]