2,4-Diaminothienopyrimidines as orally active antimalarial agents
Author(s)
Cabrera, Diego Gonzalez
Le Manach, Claire
Douelle, Frederic
Younis, Yassir
Feng, Tzu-Shean
Paquet, Tanya
Nchinda, Aloysius T
Street, Leslie J
Taylor, Dale
de Kock, Carmen
Wiesner, Lubbe
Duffy, Sandra
White, Karen L
Zabiulla, K Mohammed
Sambandan, Yuvaraj
Bashyam, Sridevi
Waterson, David
Witty, Michael J
Charman, Susan A
Avery, Vicky M
Wittlin, Sergio
Chibale, Kelly
Year published
2014
Metadata
Show full item recordAbstract
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.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.
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Journal Title
Journal of Medicinal Chemistry
Volume
57
Issue
3
Subject
Medicinal and biomolecular chemistry
Medicinal and biomolecular chemistry not elsewhere classified
Organic chemistry
Pharmacology and pharmaceutical sciences