发现 GSK143，一种高效、选择性和口服有效的脾酪氨酸激酶抑制剂。
Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.
机构信息
GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, UK.
出版信息
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. doi: 10.1016/j.bmcl.2011.07.082. Epub 2011 Aug 12.
PMID:21903390
Abstract
The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.
摘要
本文描述了二氨基嘧啶甲酰胺类脾酪氨酸激酶抑制剂的先导优化。该药物化学策略的重点是在优化人全血活性的同时，使化合物对责任激酶和 hERG 活性具有足够的选择性。化合物 GSK143 是一种有效的、高选择性的 SYK 抑制剂，在大鼠 Arthus 模型中显示出良好的疗效。
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