Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986).
Doyle K, Lönn H, Käck H, Van de Poël A, Swallow S, Gardiner P, Connolly S, Root J, Wikell C, Dahl G, Stenvall K, Johannesson P.
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.