作为强效Akt1/2抑制剂的吡啶并嘧啶的研发。
Development of pyridopyrimidines as potent Akt1/2 inhibitors.
作者信息
Wu Zhicai, Hartnett John C, Neilson Lou Anne, Robinson Ronald G, Fu Sheng, Barnett Stanley F, Defeo-Jones Deborah, Jones Raymond E, Kral Astrid M, Huber Hans E, Hartman George D, Bilodeau Mark T
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., PO Box 4, West Point, PA 19486, USA.
出版信息
Bioorg Med Chem Lett. 2008 Feb 15;18(4):1274-9. doi: 10.1016/j.bmcl.2008.01.054. Epub 2008 Jan 19.
This communication reports a new synthetic route of pyridopyrimidines to facilitate their structural optimization in a library fashion and describes the development of pyridopyrimidines that have excellent enzymatic and cell potency against Akt1 and Akt2. This series also shows a high level of selectivity over other closely related kinases and significantly improved caspase-3 activity with the more optimized compounds.
本通讯报道了一种嘧啶并吡啶的新合成路线，以利于以文库形式对其进行结构优化，并描述了对Akt1和Akt2具有优异酶活性和细胞活性的嘧啶并吡啶的开发情况。该系列化合物对其他密切相关激酶也表现出高度选择性，并且随着化合物的进一步优化，caspase-3活性显著提高。
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