brensocatib   Click here for help

GtoPdb Ligand ID: 9412

Synonyms: AZD7986 | compound 30 [1] | INS 1007 | INS1007
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Brensocatib (formerly AZD7986) is reported as a second generation, oral, selective and reversible inhibitor of dipeptidyl peptidase 1 (DPP1; a.k.a. cathepsin C) [1]. Cathepsin C is required for the activation of proinflammatory neutrophil serine proteases, making this enzyme a drug target whose pharmacological inhibition has potential in the treatment of diseases such as chronic obstructive pulmonary disease (COPD) which is driven in part by excessive neutrophil activation and dysregulated neutrophil elastase activity. The compound was originally developed by AstraZeneca, but is now being progressed by Insmed.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 109.29
Molecular weight 420.18
XLogP 2
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#CC(Cc1ccc(cc1)c1ccc2c(c1)n(C)c(=O)o2)NC(=O)C1CNCCCO1
Isomeric SMILES N#C[C@H](Cc1ccc(cc1)c1ccc2c(c1)n(C)c(=O)o2)NC(=O)[C@@H]1CNCCCO1
InChI InChI=1S/C23H24N4O4/c1-27-19-12-17(7-8-20(19)31-23(27)29)16-5-3-15(4-6-16)11-18(13-24)26-22(28)21-14-25-9-2-10-30-21/h3-8,12,18,21,25H,2,9-11,14H2,1H3,(H,26,28)/t18-,21-/m0/s1
InChI Key AEXFXNFMSAAELR-RXVVDRJESA-N
References
1. Doyle K, Lönn H, Käck H, Van de Poël A, Swallow S, Gardiner P, Connolly S, Root J, Wikell C, Dahl G et al.. (2016)
Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986).
J. Med. Chem., 59 (20): 9457-9472. [PMID:27690432]
2. Palmér R, Mäenpää J, Jauhiainen A, Larsson B, Mo J, Russell M, Root J, Prothon S, Chialda L, Forte P et al.. (2018)
Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.
Clin. Pharmacol. Ther., 104 (6): 1155-1164. [PMID:29484635]