新型基于喋啶的 LRRK2 激酶活性抑制剂。
Novel cinnoline-based inhibitors of LRRK2 kinase activity.
机构信息
Department of Medicinal Chemistry, Elan Pharmaceuticals, 180 Oyster Point Blvd, South San Francisco, CA 94080, United States.
出版信息
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。
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