title: The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection.
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.
authors.affiliation: Merck Research laboratories, Rahway, NJ 07065, USA. yusheng.xiong@merck.com
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xiong
authors.forename: Judyann
authors.initials: J
authors.lastname: Wiltsie
authors.forename: Andrea
authors.initials: A
authors.lastname: Woods
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.forename: James V
authors.initials: JV
authors.lastname: Pivnichny
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Alka
authors.initials: A
authors.lastname: Bansal
authors.forename: Richard T
authors.initials: RT
authors.lastname: Cummings
authors.forename: Barry R
authors.initials: BR
authors.lastname: Cunningham
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Friedlander
authors.forename: Cameron M
authors.initials: CM
authors.lastname: Douglas
authors.forename: Scott P
authors.initials: SP
authors.lastname: Salowe
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zaller
authors.forename: Edward M
authors.initials: EM
authors.lastname: Scolnick
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bartizal
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hermes
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy / Q000517:prevention & control; D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D008253:Macaca mulatta; D045726:Metalloproteases / Q000037:antagonists & inhibitors; D051379:Mice; D015394:Molecular Structure; D011714:Pyrans / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C509748:(2R)-2-((4-fluoro-3-methylphenyl)sulfonylamino)-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011714:Pyrans; C030325:anthrax toxin; D045726:Metalloproteases