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Synfacts 2021; 17(03): 0253
DOI: 10.1055/s-0040-1719365
Synthesis of Natural Products and Potential Drugs

Synthesis of Brensocatib (AZD7986)

Contributor(s):
Philip Kocienski
Johannesson P. * et al. AstraZeneca Gothenburg, Mölndal, Sweden
Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986).

J. Med. Chem. 2016;
59: 9457-9472
DOI: 10.1021/acs.jmedchem.6b01127.
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Key words

brensocatib - AZD7986 - dipeptidyl dipeptidase 1 inhibitor - cathepsin C inhibitor - COVID-19

Significance

Cathepsin C (CatC) is a cysteine dipeptidyl amino-peptidase that activates most tissue-degrading elastase-related serine proteases. The highlighted paper describes the discovery of brensocatib (AZD7986), a CatC inhibitor. Brensocatib is now a clinical candidate to impair protease-driven tissue degradation in COVID-19 (B. Korkmaz, A. Lesner, S. Marchand-Adam, C. Moss, D. E. Jenne J. Med. Chem. 2020, 63, 13258).


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Comment

While the paper includes some synthetic details, the potential manufacturing route depicted is taken from an earlier patent (WO 2015 110826 A1). The notable feature is the one-pot amidation (E → G) and amide dehydration reactions (G → H) used to construct the amidoacetonitrile moiety.


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Publication History

Article published online:
16 February 2021

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