Naimee Mehta1, Lori Ferrins1, Susan E Leed2, Richard J Sciotti2, Michael P Pollastri1. 1. Department of Chemistry and Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , Massachusetts 02115 , United States. 2. Experimental Therapeutics , Walter Reed Army Institute for Research , 2460 Linden Lane , Silver Spring , Maryland 20910 , United States.
Abstract
We recently reported the medicinal chemistry reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis ( Trypanosoma brucei), Chagas disease ( T. cruzi), Leishmaniasis ( Leishmania spp.), and malaria ( Plasmodium falciparum). Herein, we report our continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and molecular weight, followed by an SAR exploration, we have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961 (3).
We recently reported the medicinal chemistry reoptimization of a known human tyrosine kinase inhibitor, n class="Chemical">lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis ( Trypanosoma brucei), Chagas disease ( T. cruzi), Leishmaniasis ( Leishmania spp.), and malaria ( Plasmodium falciparum). Herein, we report our continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and molecular weight, followed by an SAR exploration, we have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961 (3).
Entities:
Keywords:
drug repurposing; malaria; target class repurposing; tropical diseases
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