Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold.

Abstract:

:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharmacological profiling of potent and highly selective kinase inhibitors based on a triazolopyridazine chemical scaffold.

journal_name

Bioorg Med Chem Lett

authors

Galatsis P,Henderson JL,Kormos BL,Han S,Kurumbail RG,Wager TT,Verhoest PR,Noell GS,Chen Y,Needle E,Berger Z,Steyn SJ,Houle C,Hirst WD

doi

10.1016/j.bmcl.2014.07.052

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

4132-40

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00776-8

journal_volume

24

pub_type

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