School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.
School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.
Bioorg Chem. 2019 Jun;87:1-11. doi: 10.1016/j.bioorg.2019.02.051. Epub 2019 Feb 25.
An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a-p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests.
描述了一种高效、一锅法和四组分合成一系列新型 2,3-二取代异吲哚啉-1-酮的方法，并评价了它们对刀豆脲酶的抑制活性。将 1,1-双(甲硫基)-2-硝基乙烯、1,2-二胺、2-甲酰苯甲酸和伯胺的混合物在乙醇中加热 3.5 小时，以良好至优异的收率得到相应的 2,3-二取代异吲哚啉-1-酮。所合成的 16 个异吲哚啉-1-酮衍生物 5a-p 均表现出脲酶抑制活性。其中，5c 的脲酶抑制活性最强（IC=10.07±0.28μM），比硫脲（IC=22.01±0.10μM）强 2 倍，比羟脲（IC=100.00±0.02μM）强 10 倍，分别作为标准抑制剂。此外，分子对接研究的结果与体外试验的结果吻合良好。
