The design and SAR of a novel series of 2-aminopyridine based LRRK2 inhibitors.

Garrick P Smith,Lassina Badolo,Victoria Chell,I-Jen Chen,Kenneth Vielsted Christensen,Laurent David,Justus Alfred Daechsel,Morten Hentzer,Martin Christian Herzig,Gitte Kobberøe Mikkelsen,Stephen P Watson,Douglas S Williamson

Bioorganic & Medicinal Chemistry Letters（2017）

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摘要

Leucine-rich repeat kinase 2 (LRRK2) has attracted considerable interest as a therapeutic target for the treatment of Parkinson’s disease. Compounds derived from a 2-aminopyridine screening hit were optimised using a LRRK2 homology model based on mixed lineage kinase 1 (MLK1), such that a 2-aminopyridine-based lead molecule 45, with in vivo activity, was identified.

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关键词

2-Aminopyridines,Parkinson’s,Homology model,LRRK2,Kinativ

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