Novel cinnoline-based inhibitors of LRRK2 kinase activity

Autor:	Colin Lorentzen, Maurizio Franzini, Anh P. Truong, R. Jeffrey Neitz, Marc Adler, Danielle L. Aubele, Pam Santiago, Hing L. Sham, Albert W. Garofalo, Simeon Bowers, Xiaocong M. Ye, Danny Tam, Kevin P. Quinn, Gary Probst, Zhao Ren, Erich Goldbach
Rok vydání:	2013
Předmět:	Clinical Biochemistry Pharmaceutical Science Protein Serine-Threonine Kinases Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Transfection Heterocyclic Compounds 2-Ring Biochemistry MAP2K7 Mice TANK-binding kinase 1 Drug Discovery Animals Humans c-Raf Kinase activity Protein Kinase Inhibitors Molecular Biology Binding Sites biology Cyclin-dependent kinase 4 Chemistry Organic Chemistry Cyclin-dependent kinase 2 Amides Protein kinase R Protein Structure Tertiary nervous system diseases Molecular Docking Simulation HEK293 Cells Mutation biology.protein Molecular Medicine Cyclin-dependent kinase 9 Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:71-74
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fde1033b8be37d0cb96bbb6c3ba3646b https://doi.org/10.1016/j.bmcl.2012.11.021 Zobrazit plný text záznamu Full Text from ScienceDirect