Prodruggability of carbohydrates — oral FimH antagonists

Schönemann, Wojciech; Kleeb, Simon; Dätwyler, Philipp; Schwardt, Oliver; Ernst, Beat

doi:10.1139/cjc-2015-0582

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Journal article

Prodruggability of carbohydrates — oral FimH antagonists

Schönemann, Wojciech Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Kleeb, Simon Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Dätwyler, Philipp Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Schwardt, Oliver Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Ernst, Beat Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.

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Canadian Journal of Chemistry. - Canadian Science Publishing. - 2016, vol. 94, no. 11, p. 909-919

English The bacterial lectin FimH is a promising therapeutic target for the nonantibiotic prevention and treatment of urinary tract infections. In this communication, an ester prodrug approach is described to achieve oral bioavailability for FimH antagonists. By introducing short-chain acyl promoieties at the C-6 position of a biphenyl α-d-mannopyranoside, prodrugs with an excellent absorption potential were obtained. The human carboxylesterase 2 was identified as a main enzyme mediating rapid bioconversion to the active principle. Despite their propensity to hydrolysis within the enterocytes during absorption, these ester prodrugs present a considerable progress in the development of orally available FimH antagonists.

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