Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, United States.
J Med Chem. 2011 Apr 14;54(7):2255-65. doi: 10.1021/jm101423y. Epub 2011 Mar 4.
The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.
一系列新型 p38α 抑制剂的研发促成了两种临床候选药物的问世，其中一种已被推进到类风湿关节炎的 2 期临床研究。最初的先导化合物是一种 lck 抑制剂，对 p38α 也具有很强的抑制作用，它是我们激酶抑制剂库中的一个筛选命中化合物。本文描述了对该先导化合物进行优化，得到了具有良好药代动力学性质的 p38 选择性化合物。
