Issue 41, 2022

Scalable synthesis and structural characterization of reversible KLK6 inhibitors

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

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
26 Jul 2022
Accepted
14 Sep 2022
First published
21 Sep 2022
This article is Open Access
Creative Commons BY license

RSC Adv., 2022,12, 26989-26993

Scalable synthesis and structural characterization of reversible KLK6 inhibitors

A. Baumann, D. Isak, J. Lohbeck, P. K. A. Jagtap, J. Hennig and A. K. Miller, RSC Adv., 2022, 12, 26989 DOI: 10.1039/D2RA04670A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements