Koechel D A, Tarloff J B, Rankin G O
J Med Chem. 1983 Jan;26(1):85-90. doi: 10.1021/jm00355a017.
Maleimidohippurates and maleimidobenzoates were synthesized that possess a carboxy group for active uptake into renal proximal tubular cells and a reactive maleimide moiety to covalently bond with proximal tubular components. The reactivity of the maleimide moiety in each series was progressively reduced by substitution of methyl groups in place of the vinyl hydrogens. In contrast to N-ethylmaleimide (NEM), the resulting maleimidohippurates and maleimidobenzoates did not possess significant diuretic activity in the dog following renal arterial administration. However, as predicted, the nephrotoxicity of the maleimidohippurates paralleled their in vitro alkylating ability and was quite specifically located in the proximal portion of the canine renal tubule.
合成了马来酰亚胺基马尿酸盐和马来酰亚胺基苯甲酸盐，它们具有一个羧基以便主动摄取进入肾近端小管细胞，以及一个活性马来酰亚胺部分以与近端小管成分共价结合。通过用甲基取代乙烯基氢，每个系列中马来酰亚胺部分的反应性逐渐降低。与N - 乙基马来酰亚胺（NEM）相反，经肾动脉给药后，所得的马来酰亚胺基马尿酸盐和马来酰亚胺基苯甲酸盐在犬中不具有显著的利尿活性。然而，正如所预测的，马来酰亚胺基马尿酸盐的肾毒性与其体外烷基化能力平行，并且非常特异性地定位于犬肾小管的近端部分。
