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Bioorg Med Chem Lett DOI:10.1016/j.bmcl.2005.10.088

The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection.

Publication TypeJournal Article
Year of Publication2006
AuthorsXiong, Y, Wiltsie, J, Woods, A, Guo, J, Pivnichny, JV, Tang, W, Bansal, A, Cummings, RT, Cunningham, BR, Friedlander, AM, Douglas, CM, Salowe, SP, Zaller, DM, Scolnick, EM, Schmatz, DM, Bartizal, K, Hermes, JD, MacCoss, M, Chapman, KT
JournalBioorg Med Chem Lett
Volume16
Issue4
Pages964-8
Date Published2006 Feb 15
ISSN0960-894X
KeywordsAnimals, Anthrax, Antigens, Bacterial, Bacterial Toxins, Biological Availability, Dogs, Drug Evaluation, Preclinical, Macaca mulatta, Metalloproteases, Mice, Molecular Structure, Pyrans, Rabbits, Stereoisomerism, Structure-Activity Relationship
Abstract

A potent and selective anthrax LF inhibitor 40, (2R)-2-[(4-fluoro-3-methylphenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, was identified through SAR study of a high throughput screen lead. It has an IC50 of 54 nM in the enzyme assay and an IC50 of 210 nM in the macrophage cytotoxicity assay. Compound 40 is also effective in vivo in several animal model studies.

DOI10.1016/j.bmcl.2005.10.088
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/16338135?dopt=Abstract

Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID16338135