Mannose-derived antagonists of FimH useful for treating disease
The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.
1. The compound of formula III, wherein formula III has the structural formula:
or a salt or ester thereof, wherein:
R 31 is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 34 ;
R 32 is chosen from H, NO 2 , NH 2 , NHR 34 ;
each R 34 is independently chosen from alkyl, aryl, and heteroaryl;
and R 35 is an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group optionally substituted with one or more of the following:
halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl.
2. A method of treatment of a FimH-mediated disease comprising the administration of a therapeutically effective amount of a compound as recited in claim 1 to a human patient in need thereof, wherein said disease is chosen from a bacterial infection, Crohn's disease (CD), and Inflammatory Bowel Disease (IBD).
3. The method as recited in claim 2 wherein said bacterial infection is a urinary tract infection.
4. The method as recited in claim 3 wherein said urinary tract infection is recurrent.
5. The method as recited in claim 3 wherein said urinary tract infection is chronic.
6. The method as recited in claim 3 wherein said bacterial infection is an antibiotic-resistant bacterial infection.
7. The method as recited in claim 2 wherein said disease is Crohn's disease.