2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas’ disease

Michael G. Thomas, Manu De Rycker, Ignacio Cotillo Torrejon, John Thomas, Jennifer Riley, Daniel Spinks, Kevin D. Read, Tim J. Miles, Ian H. Gilbert, Paul G. Wyatt (Lead / Corresponding author)

Research output: Contribution to journalArticle

48 Downloads (Pure)

Abstract

Chagas’ disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8–10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines. Demonstrating the series did not work through the anti-target TcCYP51, and was generally cytocidal, confirmed its suitability for further development. This study reports the optimisation of selectivity and metabolic stability of the series and identification of a suitable lead for further optimisation.

Original languageEnglish
Pages (from-to)3025-3030
Number of pages6
JournalBioorganic & Medicinal Chemistry Letters
Volume28
Issue number18
Early online date3 Aug 2018
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • Chagas’ disease
  • SAR studies
  • Trypanosoma cruzi

Fingerprint Dive into the research topics of '2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas’ disease'. Together they form a unique fingerprint.

  • Projects

    Profiles

    No photo of Paul Wyatt

    Wyatt, Paul

    Person: Academic

    Cite this