2,4-Diaminothienopyrimidines as orally active antimalarial agents

Diego Gonzalez Cabrera, Claire Le Manach, Frederic Douelle, Yassir Younis, Tzu-Shean Feng, Tanya Paquet, Aloysius T Nchinda, Leslie J Street, Dale Taylor, Carmen de Kock, Lubbe Wiesner, Sandra Duffy, Karen Louise White, Mohammed K Zabiulla, Yuvaraj Sambandan, Sridevi Bashyam, David Waterson, Michael J Witty, Susan Ann Charman, Vicky M AverySergio Wittlin, Kelly Chibale

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

A novel series of 2,4-diaminothienopyrimidines with potential as antimalarials was identified from whole-cell high-throughput screening of a SoftFocus ion channel library. Synthesis and structure-activity relationship studies identified compounds with potent antiplasmodial activity and low in vitro cytotoxicity. Several of these analogues exhibited in vivo activity in the Plasmodium berghei mouse model when administered orally. However, inhibition of the hERG potassium channel was identified as a liability for this series.
Original languageEnglish
Pages (from-to)1014 - 1022
Number of pages9
JournalJournal of Medicinal Chemistry
Volume57
Issue number3
DOIs
Publication statusPublished - 2014

Cite this