作为人胞质磷脂酶A2α抑制剂的1-吲哚-1-基-丙-2-酮的设计与合成
Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human cytosolic phospholipase A2alpha.
作者信息
Ludwig Joachim, Bovens Stefanie, Brauch Carsten, Elfringhoff Alwine Schulze, Lehr Matthias
机构信息
Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
出版信息
J Med Chem. 2006 Apr 20;49(8):2611-20. doi: 10.1021/jm051243a.
The synthesis and structure-activity relationship study of a series of 1-indol-1-yl-3-phenoxypropan-2-one inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) are described. The compounds were evaluated in a vesicle assay with isolated cPLA(2)alpha and in cellular assays with intact human platelets. Systematic variation led to 3-methylhydrogen 1-[3-(4-decyloxyphenoxy)-2-oxopropyl]indole-3,5-dicarboxylate (57), which revealed the highest activity against the isolated enzyme. With an IC(50) value of 4.3 nM in this assay, it is one of the most potent in vitro cPLA(2)alpha inhibitors known today.
描述了一系列1-吲哚-1-基-3-苯氧基丙-2-酮对胞质磷脂酶A(2)α（cPLA(2)α）的抑制剂的合成及其构效关系研究。这些化合物在分离的cPLA(2)α的囊泡试验以及完整人血小板的细胞试验中进行了评估。系统的变化产生了3-甲基氢1-[3-(4-癸氧基苯氧基)-2-氧代丙基]吲哚-3,5-二羧酸酯（57），其对分离的酶显示出最高活性。在该试验中，其IC(50)值为4.3 nM，是当今已知的最有效的体外cPLA(2)α抑制剂之一。
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