苯并吡喃-4-腙类化合物的合成及其血管舒张活性  

SYNTHESIS AND VASORELAXANT ACTIVITIES OF BENZOPYRAN-4-ONE HYDRAZONE DERIVATIVES

作　　者：赵圣印[1] 黄文龙[1] 张惠斌[1] 

机构地区：[1]中国药科大学新药研究中心,江苏南京210009

出　　处：《药学学报》2002年第8期621-625,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 (3 93 70 811)

摘　　要：目的　寻找高效低毒并具有组织选择性的苯并吡喃类钾通道开放剂。方法　以对氰基苯酚为原料 ,经酰化、Fries重排、环合、成腙和取代等反应合成了 3个系列 2 0个苯并吡喃 4 腙类新化合物 ,所有目标化合物结构均经IR ,1 HNMR ,MS和元素分析确证 ,并测定其对低钾 (30mmol·L- 1 KCl)和高钾 (80mmol·L- 1 KCl)诱导的大鼠主动脉条收缩抑制作用。结果　合成了 2 0个新化合物 (I1～ 9,II1～ 4 和III1～ 7)。离体扩血管活性实验表明 ,大部分化合物具有一定的血管舒张活性。结论　化合物I9,III2 和III5对低钾诱导的血管收缩抑制活性在 1× 10 - 6 mol·L- 1 浓度下略低于对照药emakalim ,但对高钾诱导的血管收缩抑制活性在浓度为 1× 10 - 5mol·L- 1 下强于对照药emakalim 。AIM In search of more potent, less toxic and selective potassium channel openers. METHODS According to the structure activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran 4 one hydrazone derivatives have been designed and synthesized from 4 cyanophenos through acetylation, Fries rearragment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol·L -1 ) and high (80 mmol·L -1 ) KCl induced contraction of rat aorta to identify potential potassium channel openers in vitro . RESULTS Three series of twenty benzopyran 4 one hydrazone derivatives, nominated N aminoacetyl (6 cyano 3,4 dihydrospiro [2H 1 benzopyran 2,1′ cyclohexane] 4) one hydrazone (I), 2 (6 cyano 3,4 dihydro 2H 1 benzopyran 4 ylene) hydrazinethiocarboxamide derivatives (II) and N (2 arylethyl) aminoacetyl (6 cyano 3,4 dihydro 2H 1 benzopyran) 4 one hydrazone (III), have been synthesized. They (I 1～9 , II 1～4 and III 1～7 ) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1×10 -6 mol·L -1 . CONCLUSION The vasorelaxant activities of compounds I 9, III 2 and III 5 in inhibiting low KCl induced vasocontraction at 1×10 -6 mol·L -1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl induced vasocontraction at 1×10 -5 mol·L -1 .It is worthy of further study.

关 键 词：苯并吡喃-4-腙类化合物 苯并吡喃 钾通道开放剂 血管舒张活性 

分 类 号：R972[医药卫生—药品] R962[医药卫生—药学]