Department of Chemistry, School of Advanced Sciences , VIT University , Vellore - 632014 , India.
Department of Chemistry, School of Advanced Sciences , VIT University , Chennai - 632014 , India.
ACS Comb Sci. 2018 Mar 12;20(3):164-171. doi: 10.1021/acscombsci.7b00173. Epub 2018 Feb 7.
An expeditious catalyst-free heteroannulation reaction for imidazo[1,2- a]pyridines/pyrimidines/pyrazines was developed in green solvent under microwave irradiation. Using HO-IPA as the reaction medium, various substituted 2-aminopyridines/pyrazines/pyrimidines underwent annulation reaction with α-bromoketones under microwave irradiation to provide the corresponding imidazo[1,2- a]pyridines/pyrimidines/pyrazines in excellent yields. The synthetic methodology appears to be very simple and superior to the already reported procedures with the high abundance of commercial reagents and great ability in expanding the molecular diversity. The present synthetic sequence is visualized as an environmentally benign process which allows the introduction of three points of structural diversity to expand chemical space with excellent purity and yields. The anti-inflammatory and antimicrobial activities of the derivatives were evaluated. Screening results uncovered three derivatives with strong inhibition of albumin denaturation and two derivatives were active on Proteus and Klebsiella bacteria. These positive bioassay results implied that the library of potential anti-inflammatory agents could be rapidly prepared in an ecofriendly manner, and provided new insights into drug discovery for medicinal chemists.
在微波辐射下，在绿色溶剂中开发了一种用于咪唑并[1,2-a]吡啶/嘧啶/吡嗪的快速无催化剂杂环化反应。使用 HO-IPA 作为反应介质，各种取代的 2-氨基吡啶/吡嗪/嘧啶与α-溴代酮在微波辐射下进行环化反应，以优异的收率得到相应的咪唑并[1,2-a]吡啶/嘧啶/吡嗪。该合成方法似乎非常简单，优于已报道的方法，具有丰富的商业试剂和扩展分子多样性的巨大能力。该合成序列被视为一种环境友好的过程，它允许引入三个结构多样性点，以优异的纯度和收率扩展化学空间。评估了衍生物的抗炎和抗菌活性。筛选结果发现有三个衍生物具有很强的抑制白蛋白变性活性，有两个衍生物对变形杆菌和肺炎克雷伯菌有活性。这些阳性生物测定结果表明，可以以环保的方式快速制备潜在抗炎剂文库，并为药物化学家提供药物发现的新见解。
