1. Nonbisphosphonate inhibitors of Plasmodium falciparum FPPS/GGPPS.
- Author
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Kabeche S, Aida J, Akther T, Ichikawa T, Ochida A, Pulkoski-Gross MJ, Smith M, Humphries PS, and Yeh E
- Subjects
- Antimalarials chemical synthesis, Antimalarials chemistry, Diphosphonates chemical synthesis, Diphosphonates chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Farnesyltranstransferase metabolism, Geranyltranstransferase metabolism, Molecular Structure, Parasitic Sensitivity Tests, Plasmodium falciparum enzymology, Structure-Activity Relationship, Antimalarials pharmacology, Diphosphonates pharmacology, Enzyme Inhibitors pharmacology, Farnesyltranstransferase antagonists & inhibitors, Geranyltranstransferase antagonists & inhibitors, Plasmodium falciparum drug effects
- Abstract
A series of novel thiazole-containing amides were synthesized. A structure-activity relationship study of these compounds led to the identification of potent and selective PfFPPS/GGPPS inhibitors with good in vitro ADME profiles. The most promising candidate molecules were progressed to mouse in vivo PK studies and demonstrated adequate free drug exposure to warrant further investigation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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