Identification of 6-amino-1H-pyrazolo[3,4-d]pyrimidines with in vivo efficacy against visceral leishmaniasis

Michael G. Thomas, Manu De Rycker, Myriam Ajakane, Sabrinia D. Crouch, Lorna Campbell, Alain Daugan, Gloria Fra, César Guerrero, Claire J. Mackenzie, Lorna MacLean, Sujatha Manthri, Franck Martin, Suzanne Norval, Maria Osuna-Cabello, Jennifer Riley, Yoko Shishikura, Juan Miguel-Siles, Frederick R. C. Simeons, Laste Stojanovski, John ThomasStephen Thompson, Raul F. Velasco, Jose M. Fiandor, Paul G. Wyatt, Kevin D. Read, Ian H. Gilbert, Timothy J. Miles

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Abstract

Visceral leishmaniasis (VL) affects millions of people across the world, largely in developing nations. It is fatal if left untreated and the current treatments are inadequate. As such, there is an urgent need for new, improved medicines. In this paper, we describe the identification of a 6-amino-N-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine scaffold and its optimization to give compounds which showed efficacy when orally dosed in a mouse model of VL.
Original languageEnglish
Number of pages10
JournalRSC Medicinal Chemistry
Early online date6 Aug 2020
DOIs
Publication statusE-pub ahead of print - 6 Aug 2020

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