Improved Synthesis of the Selected Serine Protease uPA Inhibitor UAMC-00050, a Lead Compound for the Treatment of Dry Eye Disease.

ABSTRACT: The α-aminophosphonate UAMC-00050, a newly developed trypsin-like serine protease inhibitor, is a lead compound for the treatment of dry eye syndrome and ocular inflammation. The medicinal chemistry route developed at the University of Antwerp possessed several problems hampering the scale-up such as poor yields for some of the steps, hazardous reagents, and environmental footprint. Herein, we report an optimized route for the UAMC-00050, in which environmental unfriendly solvents were excluded, hazardous reagents were replaced with safer alternatives, and are more efficient in terms of atom economy. Every reaction step was optimized to reach a higher yield, and design of experiment was used to find the optimum conditions in the last step. Furthermore, all the flash chromatography purifica

SUBMITTER: Ceradini D 

PROVIDER: S-EPMC9594321 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature