新型强效和高选择性的 GVIA 钙非依赖性磷脂酶 A2 的多氟烷基酮抑制剂。
New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A2.
机构信息
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Greece.
出版信息
Bioorg Med Chem. 2013 Sep 15;21(18):5823-9. doi: 10.1016/j.bmc.2013.07.010. Epub 2013 Jul 16.
Abstract
Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA2 inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA2 inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA2 inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA2 or GV sPLA2. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA2, GIVA cPLA2, and GV sPLA2.
摘要
Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) 最近已成为一个重要的药物靶点。选择性和有效的 GVIA iPLA2 抑制剂可用于研究其在各种神经疾病中的作用。在目前的工作中，我们探讨了在以前报道的有效的 GVIA iPLA2 抑制剂中引入取代基的意义。1,1,1,2,2-五氟-7-(4-甲氧基苯基)庚烷-3-酮 (GK187) 是迄今为止报道的最有效和选择性的 GVIA iPLA2 抑制剂，其 XI(50) 值为 0.0001，对 GIVA cPLA2 或 GV sPLA2 没有明显的抑制作用。我们还比较了两种二氟甲基酮对 GVIA iPLA2、GIVA cPLA2 和 GV sPLA2 的抑制作用。
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