We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from . The current work, through structure-activity relationship studies, led to the discovery of compounds ( and ) with improved characteristics over the starting inhibitor in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds and were further demonstrated to be more effective than in a mouse infection model and markedly reduced the amount of in the brain, spleen, and peritoneal fluid, and given at 20 mg/kg eliminated from the peritoneal fluid.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677665 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.5b00319 | DOI Listing |
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