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Identification of 6-amino-1H-pyrazolo[3,4-d]pyrimidines with in vivo efficacy against visceral leishmaniasis
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-08-06 , DOI: 10.1039/d0md00203h Michael G Thomas 1 , Manu De Rycker 1 , Myriam Ajakane 2 , Sabrinia D Crouch 3 , Lorna Campbell 1 , Alain Daugan 2 , Gloria Fra 4 , César Guerrero 4 , Claire J Mackenzie 1 , Lorna MacLean 1 , Sujatha Manthri 1 , Franck Martin 2 , Suzanne Norval 1 , Maria Osuna-Cabello 1 , Jennifer Riley 1 , Yoko Shishikura 1 , Juan Miguel-Siles 3 , Frederick R C Simeons 1 , Laste Stojanovski 1 , John Thomas 1 , Stephen Thompson 1 , Raul F Velasco 4 , Jose M Fiandor 3 , Paul G Wyatt 1 , Kevin D Read 1 , Ian H Gilbert 1 , Timothy J Miles 3
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-08-06 , DOI: 10.1039/d0md00203h Michael G Thomas 1 , Manu De Rycker 1 , Myriam Ajakane 2 , Sabrinia D Crouch 3 , Lorna Campbell 1 , Alain Daugan 2 , Gloria Fra 4 , César Guerrero 4 , Claire J Mackenzie 1 , Lorna MacLean 1 , Sujatha Manthri 1 , Franck Martin 2 , Suzanne Norval 1 , Maria Osuna-Cabello 1 , Jennifer Riley 1 , Yoko Shishikura 1 , Juan Miguel-Siles 3 , Frederick R C Simeons 1 , Laste Stojanovski 1 , John Thomas 1 , Stephen Thompson 1 , Raul F Velasco 4 , Jose M Fiandor 3 , Paul G Wyatt 1 , Kevin D Read 1 , Ian H Gilbert 1 , Timothy J Miles 3
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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.
更新日期：2020-08-06
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