2,4-diaminothienopyrimidines as orally active antimalarial agents

13 Feb 2014

Diego González 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 L. White, K. Mohammed Zabiulla, Yuvaraj Sambandan, Sridevi Bashyam, David Waterson, Michael J. Witty, Susan A. Charman, Vicky M. Avery, Sergio Wittlin, and Kelly Chibale

Journal of Medicinal Chemistry
DOI: 10.1021/jm401760c

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.

Read the full article on the ACS publications website.