含脲基苯并呋喃酮部分的 4-取代-7-氮杂吲哚作为新型有效的哺乳动物雷帕霉素靶蛋白（mTOR）ATP 竞争性抑制剂。
4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR).
机构信息
Chemical Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, United States.
出版信息
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2259-63. doi: 10.1016/j.bmcl.2010.02.012. Epub 2010 Feb 6.
PMID:20188551
Abstract
A series of 5-ureidobenzofuranones was discovered as potent and selective inhibitors of mTOR with good cellular activity. Molecular modeling studies revealed several hydrogen bond interactions of the ureido group with the enzyme at the ATP-binding site. Furthermore, modeling showed that the ureido group is best situated at C-5 of the benzofuranone. Syntheses of 4-ureido and 5-ureidobenzofuranones are presented.
摘要
一系列 5-脒基苯并呋喃酮被发现是强效和选择性的 mTOR 抑制剂，具有良好的细胞活性。分子建模研究揭示了脒基与酶在 ATP 结合部位的几个氢键相互作用。此外，建模表明脒基最好位于苯并呋喃酮的 C-5 位。本文介绍了 4-脒基和 5-脒基苯并呋喃酮的合成。
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