A series of novel sulfonates containing quinazolin-4(3H)-one ring derivatives was designed to inhibit aldose reductase (ALR2, EC 1.1.1.21). Novel quinazolinone derivatives (1–21) were synthesized from the reaction of sulfonated aldehydes with 3-amino-2-alkylquinazolin-4(3H)-ones in glacial acetic acid with good yields (85%–94%). The structures of the novel molecules were characterized using IR, ¹H-NMR, ¹³C-NMR, and HRMS. All the novel quinazolinones (1–21) demonstrated nanomolar levels of inhibitory activity against ALR2 (K_Is are in the range of 101.50–2066.00 nM). Besides, 4-[(2-isopropyl-4-oxoquinazolin-3[4H]-ylimino)methyl]phenyl benzenesulfonate (15) showed higher inhibitor activity inhibited ALR2 up to 7.7-fold compared to epalrestat, a standard inhibitor. Binding interactions between ALR2 and quinazolinones have been investigated using Schrödinger Small-Molecule Drug Discovery Suite 2021–1, reported possible inhibitor-ALR2 interactions. Both in vitro and in silico study results suggest that these quinazolin-4(3H)-one ring derivatives (1–21) require further molecular modification to improve their drug nominee potency as an ALR2 inhibitor.

中文翻译：

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作为潜在醛糖还原酶抑制剂的含有喹唑啉-4(3H)-一衍生物的新型磺酸盐库的合成、生物学评价和计算机研究

一系列含有喹唑啉-4(3 H )-酮环衍生物的新型磺酸盐被设计用于抑制醛糖还原酶（ALR2，EC 1.1.1.21）。磺化醛与 3-氨基-2-烷基喹唑啉-4(3 H )-酮在冰醋酸中反应合成了新型喹唑啉酮衍生物 ( 1–21 )，收率良好 (85%–94%)。^{使用IR、 1H} -NMR、^13C -NMR和HRMS对新型分子的结构进行了表征。所有新型喹唑啉酮 ( 1-21 ) 均表现出纳摩尔水平的 ALR2 抑制活性（K _I范围为 101.50-2066.00 nM）。此外，与标准抑制剂依帕司他相比，4-[(2-异丙基-4-氧代喹唑啉-3[4 H ]-基亚氨基)甲基]苯基苯磺酸盐( 15 )表现出更高的抑制剂活性，对ALR2的抑制高达7.7倍。使用薛定谔小分子药物发现套件 2021-1 研究了 ALR2 和喹唑啉酮之间的结合相互作用，报告了可能的抑制剂与 ALR2 相互作用。体外和计算机研究结果表明，这些 quinazolin-4(3 H )-one 环衍生物 ( 1-21 ) 需要进一步的分子修饰，以提高其作为 ALR2 抑制剂的药物提名效力。