Synthesis and evaluation of thiomannosides, potent and orally active FimH inhibitors

Bioorganic & Medicinal Chemistry Letters
Jitendra A SattigeriTakahide Nishi

Abstract

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coli (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally. Especially compound 5h showed the potential to inhibit biofilm formation and also to disrupt the preformed biofilm. And compound 5h showed prophylactic effect in UTI model in mice.

Citations

Aug 31, 2019·Current Opinion in Chemical Biology·Joscha MeiersAlexander Titz
Mar 16, 2019·EcoSal Plus·John J Psonis, David G Thanassi
Jun 20, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Sivapriya KirubakaranSrinivasan Chandrasekaran
Dec 14, 2018·Journal of the American Chemical Society·Maximilian M SauerRudi Glockshuber

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