Department of Medicinal Chemistry, Elan Pharmaceuticals, 180 Oyster Point Blvd, South San Francisco, CA 94080, United States.
Bioorg Med Chem Lett. 2013 Jan 1;23(1):71-4. doi: 10.1016/j.bmcl.2012.11.021. Epub 2012 Nov 16.
Leucine rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson's disease (PD). Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD. Herein we report the discovery of a series of cinnoline-3-carboxamides that are potent against both wild-type and mutant LRRK2 kinase activity in biochemical assays. These compounds are also shown to be potent inhibitors in a cellular assay and to have good to excellent CNS penetration.
富含亮氨酸重复激酶 2（LRRK2）与帕金森病（PD）的发病机制有关。抑制 LRRK2 激酶活性是一种可能为 PD 带来新治疗方法的治疗方法。本文报道了一系列嘧啶并[3,4-d]嘧啶-3-甲酰胺的发现，它们在生化测定中对野生型和突变型 LRRK2 激酶活性均具有很强的抑制作用。这些化合物在细胞测定中也表现出很强的抑制作用，并且具有良好到优秀的中枢神经系统穿透性。
