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

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

  • Bioorg Med Chem Lett. 2014 Sep 1;24(17):4132-40. doi: 10.1016/j.bmcl.2014.07.052.
Paul Galatsis 1,  Jaclyn L Henderson 2,  Bethany L Kormos 2,  Seungil Han 3,  Ravi G Kurumbail 3,  Travis T Wager 2,  Patrick R Verhoest 2,  G Stephen Noell 4,  Yi Chen 5,  Elie Needle 5,  Zdenek Berger 5,  Stefanus J Steyn 6,  Christopher Houle 7,  Warren D Hirst 5
Affiliations

Affiliations

  • 1 Worldwide Medicinal Chemistry, Pfizer Worldwide R&D, 610 Main St., Cambridge, MA 02139, United States. Electronic address: paul.galatsis@pfizer.com.
  • 2 Worldwide Medicinal Chemistry, Pfizer Worldwide R&D, 610 Main St., Cambridge, MA 02139, United States.
  • 3 Worldwide Medicinal Chemistry, Pfizer Worldwide R&D, Eastern Point Rd., Groton, CT 06340, United States.
  • 4 Primary Pharmacology Group, Pfizer Worldwide R&D, Eastern Point Rd., Groton, CT 06340, United States.
  • 5 Neuroscience Research Unit, Pfizer Worldwide R&D, 610 Main St., Cambridge, MA 02139, United States.
  • 6 Pharmacokinetics, Dynamics, and Metabolism, Pfizer Worldwide R&D, 610 Main St., Cambridge, MA 02139, United States.
  • 7 Drug Safety R&D, Pfizer Worldwide R&D, Eastern Point Rd., Groton, CT 06340, United States.
PMID: 25113930 DOI: 10.1016/j.bmcl.2014.07.052
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.

Keywords

Kinase inhibitors; LRRK2; Leucine rich repeat kinase 2; Triazolopyridazine.

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