1295649-86-3Relevant academic research and scientific papers
Antivirulence C-Mannosides as Antibiotic-Sparing, Oral Therapeutics for Urinary Tract Infections
Mydock-McGrane, Laurel,Cusumano, Zachary,Han, Zhenfu,Binkley, Jana,Kostakioti, Maria,Hannan, Thomas,Pinkner, Jerome S.,Klein, Roger,Kalas, Vasilios,Crowley, Jan,Rath, Nigam P.,Hultgren, Scott J.,Janetka, James W.
, p. 9390 - 9408 (2016/11/11)
Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models of UTI but were found to have limited compound exposure due to the metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having the O-glycosidic bond replaced with carbon linkages had improved stability and inhibitory activity against FimH. We report on the design, synthesis, and in vivo evaluation of this promising new class of carbon-linked C-mannosides that show improved pharmacokinetic (PK) properties relative to O-mannosides. Interestingly, we found that FimH binding is stereospecifically modulated by hydroxyl substitution on the methylene linker, where the R-hydroxy isomer has a 60-fold increase in potency. This new class of C-mannoside antagonists have significantly increased compound exposure and, as a result, enhanced efficacy in mouse models of acute and chronic UTI.
COMPOUNDS AND METHODS FOR TREATING BACTERIAL INFECTIONS
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Sheet 52/58, (2014/12/12)
The present invention encompasses compounds and methods for treating and preventing bacterial infections specifically urinary tract infections and those caused by bacteria containing type 1 pili and FimH. The present invention also encompasses compounds and methods for treating inflammatory bowel disease specifically Crohn's Disease.
COMPOUNDS AND METHODS FOR TREATING BACTERIAL INFECTIONS
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Page/Page column 66, (2011/05/06)
The present invention encompasses compounds and methods for treating urinary tract infections.
