Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

Wenhui Hu, Hantamalala Ralay Ranaivo, Saktimayee M. Roy, Heather A. Behanna, Laura K. Wing, Lenka Munoz, Ling Guo, Linda J. Van Eldik, D. Martin Watterson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

Original languageEnglish (US)
Pages (from-to)414-418
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number2
DOIs
StatePublished - Jan 15 2007

Keywords

  • Alzheimer's disease
  • Neurodegeneration
  • Process chemistry
  • Proinflammatory cytokine
  • Pyridazine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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