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Bioorg Med Chem Lett. 2013 Feb 15;23(4):1004-7. doi: 10.1016/j.bmcl.2012.12.037. Epub 2012 Dec 27.

Phthalazinone inhibitors of inosine-5'-monophosphate dehydrogenase from Cryptosporidium parvum.

Author information

1
Department of Chemistry, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA.

Abstract

Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.

PMID:
23324406
PMCID:
PMC3557747
DOI:
10.1016/j.bmcl.2012.12.037
[Indexed for MEDLINE]
Free PMC Article

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