Dipartimento Farmaco-chimico, University of Messina, Polo Universitario dell'Annunziata, 98168 Messina, Italy.
Bioorg Med Chem. 2010 Jun 1;18(11):4049-55. doi: 10.1016/j.bmc.2010.04.016. Epub 2010 Apr 9.
Non-carboxylic acid containing bioisosteres of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetic acids, which are active as aldose reductase (ALR2) inhibitors, were designed by replacing the carboxylic group with the trifluoromethyl ketone moiety. The in vitro evaluation of the ALR2 inhibitory effects of these trifluoromethyl substituted derivatives led to the identification of two inhibitors effective at low micromolar doses. It was further confirmed that a carboxylic chain on N-3 of the thiazolidinedione scaffold is a determining requisite to obtain the highest efficacy levels; however, it is not essential for the interaction with the target enzyme and it can be replaced by different polar groups, thus obtaining less ionised or unionised inhibitors.
非羧酸类（5-亚芳基-2,4-二氧代噻唑烷-3-基）乙酸生物等排体是醛糖还原酶（ALR2）抑制剂，通过用三氟甲基酮取代羧酸基团进行设计。对这些三氟甲基取代衍生物的 ALR2 抑制作用的体外评估导致鉴定出两种在低微摩尔剂量下有效的抑制剂。进一步证实，噻唑烷二酮支架上 N-3 的羧酸链是获得最高疗效水平的决定因素；然而，它对于与靶酶的相互作用不是必需的，并且可以被不同的极性基团取代，从而获得较少离子化或非离子化的抑制剂。
