MRC Technology, Centre for Therapeutics Discovery, 1-3 Burtonhole Lane, Mill Hill, London, NW7 1AD, UK.
Bioorg Med Chem Lett. 2012 Dec 1;22(23):7169-73. doi: 10.1016/j.bmcl.2012.09.063. Epub 2012 Sep 28.
The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKε pathway in inflammatory diseases.
本研究描述了一系列新型 2,4-二氨基-5-环丙基嘧啶的设计、合成和构效关系。以最初报道的 PDK1 强效抑制剂 BX795 为起始物，我们开发出了具有更好选择性和类药性的化合物。这些化合物已在一系列细胞和体内实验中进行了评估，使我们能够探究 TBK1/IKKε 通路在炎症性疾病中的潜在作用。
