Inhibition of ketohexokinase (KHK, fructokinase) leads to decrease in fructose metabolism and may provide a new treatment option for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A scalable route was developed to access bulk quantities of the [3.1.0] amino acid fragment used in the synthesis of Pfizer’s ketohexokinase (KHK) inhibitor. The route utilized an advanced amino-alcohol intermediate and homologation chemistry to furnish the final [3.1.0] amino ester monomer in 93% yield in 4 steps as an isolable solid without chromatography. This route was used to deliver 100 g of the monomer in house and an additional 700 g at a vendor. The resultant material was utilized to synthesize &gt;450 g of final API.

Synthesis of the [3.1.0] amino acid fragment of a ketohexokinase inhibitor for the treatment of NAFLD/NASH

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.