2,4-diaminothienopyrimidines as orally active antimalarial agents

From:
Department for International Development
Published
1 January 2014
Document Type:
Journal Article
Theme:
Health
Authors:
Taylor, D., Waterson, D., Charman, S.A., White, K.L., Wittlin, S., Chibale, K., Douelle, F., González Cabrera, D., Nchinda, A.T., Witty, M.J., Younis, Y., Bashyam, S., Duffy, S., Le Manach, C., de Kock, C., Feng TzuShean, Street, L.J., Paquet, T., Avery, V.M., Mohammed Zabuilla, K., Sambandan, Y., Wiesner, L.

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.

Citation

González Cabrera, D.; Le Manach, C.; Douelle, F.; Younis, Y.; Feng TzuShean; Paquet, T.; Nchinda, A.T.; Street, L.J.; Taylor, D.; de Kock, C.; Wiesner, L.; Duffy, S.; White, K.L.; Mohammed Zabuilla, K.; Sambandan, Y.; Bashyam, S.; Waterson, D.; Witty, M.J.; Charman, S.A.; Avery, V.M.; Wittlin, S.; Chibale, K. 2,4-Diaminothienopyrimidines as Orally Active Antimalarial Agents. Journal of Medicinal Chemistry (2014) 57 (3) 1014-1022. [DOI: 10.1021/jm401760c]

2,4-diaminothienopyrimidines as orally active antimalarial agents

Published 1 January 2014
Contents