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发现咪唑乙烯基嘧啶作为一类新型激酶抑制剂，可抑制Tie-2且具有口服生物利用度。

Discovery of imidazole vinyl pyrimidines as a novel class of kinase inhibitors which inhibit Tie-2 and are orally bioavailable.

作者信息

Buttar David, Edge Mike, Emery Steve C, Fitzek Martina, Forder Cheryl, Griffen Alison, Hayter Barry, Hayward Chris F, Hopcroft Philip J, Luke Richard W A, Page Ken, Stawpert John, Wright Andy

机构信息

Cancer and Infection Research Area, Mereside, Alderley Park, AstraZeneca, Macclesfield SK10 4TG, UK.

出版信息

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4723-6. doi: 10.1016/j.bmcl.2008.06.106. Epub 2008 Jul 23.

DOI:10.1016/j.bmcl.2008.06.106
PMID:18676144
Abstract

Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines. These compounds are lead-like, with low molecular weight, good physical properties and oral bioavailability.

摘要

Tie-2是一种受体酪氨酸激酶，参与血管生成，进而影响人类肿瘤的生长。本文报道了一类新型咪唑-乙烯基-嘧啶激酶抑制剂的发现及其构效关系，这类抑制剂在体外可抑制Tie-2。它们通过咪唑醛与甲基嘧啶缩合来合成。这些化合物具有类先导物的性质，分子量低，物理性质良好且具有口服生物利用度。

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