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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.

SUBMITTER: Baumann A

PROVIDER: S-EPMC9490775 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Scalable synthesis and structural characterization of reversible KLK6 inhibitors.

Baumann Andreas A Isak Daniel D Lohbeck Jasmin J Jagtap Pravin Kumar Ankush PKA Hennig Janosch J Miller Aubry K AK

RSC advances 20220921 41

Scalable asymmetric syntheses of two kallikrein-related protease 6 (KLK6) inhibitors are reported. The inhibitors are assembled by linking enantiomerically enriched fragments <i>via</i> 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 <i>via</i> X-ray crystallographic analysis of two derivatives. Comp ...[more]

PMID: 36320846

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