Medicinal Chemistry, Pfizer, 200 Cambridge Park Drive, Cambridge, MA 02140, United States.
Bioorg Med Chem Lett. 2011 Nov 1;21(21):6258-63. doi: 10.1016/j.bmcl.2011.09.008. Epub 2011 Sep 10.
Imidazo[1,5-a]quinoxalines were synthesized that function as irreversible Bruton's tyrosine kinase (BTK) inhibitors. The syntheses and SAR of this series of compounds are presented as well as the X-ray crystal structure of the lead compound 36 in complex with a gate-keeper variant of ITK enzyme. The lead compound showed good in vivo efficacy in preclinical RA models.
合成了咪唑并[1,5-a]喹喔啉类化合物，它们可作为不可逆的布鲁顿酪氨酸激酶（BTK）抑制剂。本文介绍了该系列化合物的合成和构效关系，以及先导化合物 36 与 ITK 酶的变构抑制剂复合物的 X 射线晶体结构。该先导化合物在类风湿关节炎的临床前模型中显示出良好的体内疗效。
