Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
Bioorg Med Chem. 2010 Jan 15;18(2):945-52. doi: 10.1016/j.bmc.2009.11.028. Epub 2009 Nov 17.
Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) and fatty acid amide hydrolase (FAAH) are enzymes, which have emerged as attractive targets for the development of analgetic and anti-inflammatory drugs. We recently reported that 1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (10) and related compounds are inhibitors of cPLA(2)alpha. Since cPLA(2)alpha and FAAH possess several common structural features, we now screened this substance series together with some new derivatives for FAAH inhibition. Some of the assayed compounds proved to be selective cPLA(2)alpha inhibitors, while others showed high FAAH and moderate cPLA(2)alpha inhibitory potency. Furthermore, several derivatives were favorably active against both enzymes and, therefore, could represent agents, which have improved analgetic and anti-inflammatory qualities in comparison with selective cPLA(2)alpha and FAAH inhibitors.
细胞质型磷脂酶 A(2)α(cPLA(2)α)和脂肪酸酰胺水解酶(FAAH)是两种酶，它们已成为开发镇痛和抗炎药物的有吸引力的靶点。我们最近报道，1-[3-(4-辛基苯氧基)-2-氧代丙基]吲哚-5-羧酸(10)和相关化合物是 cPLA(2)α 的抑制剂。由于 cPLA(2)α 和 FAAH 具有一些共同的结构特征，我们现在一起筛选了这个化合物系列以及一些新的衍生物对 FAAH 的抑制作用。一些被测试的化合物被证明是选择性 cPLA(2)α 抑制剂，而其他化合物则对 FAAH 具有高抑制活性和中等的 cPLA(2)α 抑制活性。此外，一些衍生物对两种酶都有很好的活性，因此与选择性 cPLA(2)α 和 FAAH 抑制剂相比，它们可能代表具有改善的镇痛和抗炎特性的药物。
