Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran.
Bioorg Chem. 2012 Apr-Jun;41-42:22-7. doi: 10.1016/j.bioorg.2012.01.003. Epub 2012 Feb 1.
A novel method has been developed for the synthesis of 1-ureidophosphonates through a three components condensation of aldehyde with amine and diethylphosphite in the presence of sulfanilic acid as catalyst followed by subsequent reaction of the product with isocyanate. This method is easy, rapid, and good yielding. The anticholinesterase (AChE) activities (inhibition potency through IC(50)) of newly synthesized 1-ureidophosphonates were also investigated. The activities of the synthesized compounds toward the enzyme AChE were determined and compared in terms of their molecular structures and it was found, through molecular docking simulations, that the most potent derivative (compound 3i) inhibited the enzyme through binding to the peripheral anionic site (PAS) and not to its acylation site (A site).
一种新方法已经被开发出来，用于通过醛与胺和亚磷酸二乙酯在磺胺酸作为催化剂的存在下的三组分缩合来合成 1-脒基膦酸酯，然后使产物与异氰酸酯进一步反应。该方法简单、快速、产率高。新合成的 1-脒基膦酸酯的抗胆碱酯酶 (AChE) 活性（通过 IC50 表示的抑制能力）也进行了研究。通过分子对接模拟，根据合成化合物的分子结构来确定它们对酶 AChE 的活性，并发现最有效的衍生物（化合物 3i）通过与外周阴离子结合位点 (PAS) 而不是其酰化位点 (A 位点) 结合来抑制该酶。
