Insecticidal lead identification by screening benzopyrano[4,3-c] pyrazol-3(2H)-ones library constructed from multiple-parallel synthesis under microwave irradiation.
Insecticidal lead identification by screening benzopyrano[4,3-c] pyrazol-3(2H)-ones library constructed from multiple-parallel synthesis under microwave irradiation.
复制标题
DOI：
10.1016/j.bmc.2006.08.020
复制
发表时间：
2006-12
影响因子：
3.5
通讯作者：
Zhong-Zheng Zhou;Guangfu Yang
中科院分区：
文献类型：
--
作者：
Zhong-Zheng Zhou;Guangfu Yang
以苯并吡喃酮-3-羧酸为起始原料，在微波辐射下，采用液相多重平行法快速合成了2-取代苄基-1-苯并吡喃并[4，3-c]吡唑-3（2 H）-酮化合物。与传统平行合成方法相比，微波辅助平行合成方法大大缩短了反应时间，平均反应时间从16 h缩短到13 min，产物和中间体的产率在大多数情况下都得到了提高。生物活性测定结果表明，化合物库中的化合物具有良好的杀虫活性。在250 mgL-1的剂量下，化合物对朱砂根具有杀虫活性，部分化合物在50 mgL-1剂量下仍具有杀虫活性。这表明2-（取代的）苄基-1-苯并吡喃并[4，3-c]吡唑-3（2 H）-酮可以作为先导结构用于进一步优化。据我们所知，这是第一个报告，在微波辐射下的液相多平行合成的应用，以构建具有杀虫活性的苯并吡喃-[4，3-c]吡唑-3（2 H）-酮类化合物库。微波技术与液相平行合成的耦合构成了一种新颖的，特别有吸引力的途径，用于快速生成结构多样的图书馆，以发现铅。
A rapid library-generation via liquid-phase multiple-parallel synthesis of 2-(substituted)benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones, bearing two points of diversity, under microwave irradiation was successfully performed using chromenone-3-carboxylic acids as starting materials. Compared to an identical library generated by conventional parallel synthesis, microwave-assisted parallel synthesis dramatically decreased reaction times from an average of 16h to 13min, and the yields of products and intermediates were improved in most cases. A bioassay indicated that the compounds of the library exhibited excellent insecticidal activity against T. cinnabarinus at the dosage of 250mgL−1, and some compounds still exhibited insecticidal activity when the dosage was reduced to 50mgL−1. This shows that 2-(substituted) benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones might be used as lead structures for further optimization. To our knowledge, this is the first report about the application of solution-phase multiple-parallel synthesis under microwave irradiation to construct libraries of benzopyrano-[4,3-c]pyrazol-3(2H)-ones with insecticidal activity. The coupling of microwave technology with liquid-phase parallel synthesis constitutes a novel and particularly attractive avenue for the rapid generation of structurally diverse libraries for lead discovery.