Scalable synthesis and structural characterization of reversible KLK6 inhibitors?

RSC Advances Pub Date: 2022-09-21 DOI: 10.1039/D2RA04670A

Abstract

Scalable asymmetric syntheses of two kallikrein-related protease 6 (KLK6) inhibitors are reported. The inhibitors are assembled by linking enantiomerically enriched fragments via amide bond formation, followed by conversion of a cyano group to an amidine. One fragment, an amine, was prepared using the Ellman auxiliary, and a lack of clarity in the literature regarding the stereochemical outcome of this reaction was solved via X-ray crystallographic analysis of two derivatives. Complexes of the inhibitors bound to human KLK6 were solved by X-ray crystallography, revealing the binding poses.

Graphical abstract: Scalable synthesis and structural characterization of reversible KLK6 inhibitors
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