2. Academic Validation
  3. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986)

Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986)

  • J Med Chem. 2016 Oct 27;59(20):9457-9472. doi: 10.1021/acs.jmedchem.6b01127.
Kevin Doyle 1,  Hans Lönn 2,  Helena Käck 2,  Amanda Van de Poël 1,  Steve Swallow 3,  Philip Gardiner 2,  Stephen Connolly 2,  James Root 2,  Cecilia Wikell 2,  Göran Dahl 2,  Kristina Stenvall 2,  Petra Johannesson 2
Affiliations

Affiliations

  • 1 Discovery, Charles River , Chesterford Research Park, Saffron Walden, Essex CB10 1XL, U.K.
  • 2 AstraZeneca Gothenburg , Pepparedsleden 1, Mölndal 431 83, Sweden.
  • 3 AstraZeneca Alderley Park , Macclesfield, Cheshire SK10 4TG, U.K.
PMID: 27690432 DOI: 10.1021/acs.jmedchem.6b01127
Abstract

A novel series of second generation DPP1 inhibitors free from aorta binding liabilities found for earlier compound series was discovered. This work culminated in the identification of compound 30 (AZD7986) as a highly potent, reversible, and selective clinical candidate for COPD, with predicted human PK properties suitable for once daily human dosing.

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