Structure guided modification of 2-chloro-5-(ethyl-phenyl-sulfamoyl)-N-[2-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide to afford selective inhibitors of Cryptosporidium parvum N-myristoyltransferase.

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Tác giả: Erkang Fan, Michael K Fenwick, Sophia Groustra, Matthew A Hulverson, Monique Khim, Eric Owsley, Sayaka Shibata, Dilep K Sigalapalli, Bart L Staker, Wesley C Van Voorhis, Rachael Zigweid

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Bioorganic & medicinal chemistry letters , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 253585

Cryptosporidium parvum is a protozoan parasite that causes severe diarrheal illness in children and each year nearly 50,000 children under age 5 die due to the disease. Despite tremendous research efforts, there remains a lack of effective therapies and vaccines. Novel inhibitors against N-myristoyltransferase of C. parvum (CpNMT) are potential starting points towards the development of effective therapies. In quest of promising selective CpNMT inhibitors, structure guided modifications of compound 1 (2-chloro-5-(ethyl-phenyl-sulfamoyl)-N-[2-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide) were performed. The resulting compounds were evaluated for selective inhibition of CpNMT over the host enzyme HsNMT1. Compounds 11e and 11f exhibited good inhibition, with IC
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