Haffner Curt D, Diaz Caroline J, Miller Aaron B, Reid Robert A, Madauss Kevin P, Hassell Annie, Hanlon Mary H, Porter David J T, Becherer J David, Carter Luke H
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Bioorg Med Chem Lett. 2008 Aug 1;18(15):4360-3. doi: 10.1016/j.bmcl.2008.06.067. Epub 2008 Jun 24.
We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket.
我们报告了一系列新型吡咯烷基吡啶酮和吡嗪酮作为脯氨酰寡肽酶（POP）强效抑制剂的合成及体外活性。在该系列化合物中，化合物39与人嵌合POP蛋白的催化位点共结晶，这为更详细地了解这些抑制剂如何与催化口袋内的关键残基相互作用提供了依据。
