KDR激酶的噻吩并吡啶脲抑制剂。
Thienopyridine urea inhibitors of KDR kinase.
作者信息
Heyman H Robin, Frey Robin R, Bousquet Peter F, Cunha George A, Moskey Maria D, Ahmed Asma A, Soni Niru B, Marcotte Patrick A, Pease Lori J, Glaser Keith B, Yates Melinda, Bouska Jennifer J, Albert Daniel H, Black-Schaefer Candace L, Dandliker Peter J, Stewart Kent D, Rafferty Paul, Davidsen Steven K, Michaelides Michael R, Curtin Michael L
机构信息
Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA.
出版信息
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1246-9. doi: 10.1016/j.bmcl.2006.12.015. Epub 2006 Dec 9.
A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.
制备了一系列取代噻吩并吡啶脲，并对其抑制KDR激酶活性的酶促作用和细胞作用进行了评估。其中几种类似物，如化合物2，在酶促试验和细胞试验中都是KDR的有效抑制剂（<10 nM）。对抑制剂2的进一步表征表明，在雌二醇诱导的小鼠子宫水肿模型中测定，该类似物具有优异的体内活性（半数有效剂量为2.1 mg/kg）。
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