2-Oxotetrahydroquinoline-based antimalarials with high potency and metabolic stability

Journal of Medicinal Chemistry
Vivek J BulbuleMichael H Gelb

Abstract

We report a series of novel inhibitors of protein farnesyltransferase based on the 2-oxotetrahydroquinoline scaffold. We developed an efficient synthesis of these compounds. These compounds show selective inhibtion of the malaria versus human farnesyltransferase and inhibit the growth of the malaria parasite in the low nanomolar range. Some of the compounds are at least an order of magnitude more stable to metabolic degradation than the corresponding tetrahydroquinolines.

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Citations

Aug 13, 2011·Chemical Reviews·Vellaisamy SridharanJ Carlos Menéndez
Mar 12, 2013·Acta Crystallographica. Section E, Structure Reports Online·Josephus Jacobus de Jager, Vincent J Smith
Jul 25, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Can ChenQinglin Jiang
Mar 1, 2013·MedChemComm·Joshua D Ochocki, Mark D Distefano
Jun 26, 2013·Acta Crystallographica. Section E, Structure Reports Online·Mu-Hua HuangYun-Jun Luo
Jun 9, 2009·Journal of Chemical Theory and Computation·Ming-Hsun HoMichael L Klein

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Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.