Kim Kyoung Soon, Lu Songfeng, Cornelius Lyndon A, Lombardo Louis J, Borzilleri Robert M, Schroeder Gretchen M, Sheng Christopher, Rovnyak George, Crews Donald, Schmidt Robert J, Williams David K, Bhide Rajeev S, Traeger Sarah C, McDonnell Patricia A, Mueller Luciano, Sheriff Steven, Newitt John A, Pudzianowski Andrew T, Yang Zheng, Wild Robert, Lee Frances Y, Batorsky Roberta, Ryder James S, Ortega-Nanos Marie, Shen Henry, Gottardis Marco, Roussell Deborah L
Department of Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Bioorg Med Chem Lett. 2006 Aug 1;16(15):3937-42. doi: 10.1016/j.bmcl.2006.05.037. Epub 2006 May 30.
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein.
本文描述了作为Eg5抑制剂的取代吡咯并三嗪-4-酮类似物的合成及其构效关系。这些类似物中的许多在Eg5 ATP酶和A2780细胞增殖试验中表现出强效抑制活性。此外，吡咯并三嗪-4-酮类似物26在静脉注射P388小鼠白血病模型中显示出体内疗效。核磁共振（NMR）和X射线晶体学研究均表明，这些类似物与Eg5蛋白上的一个别构位点结合。
