alvelestat   Click here for help

GtoPdb Ligand ID: 6476

Synonyms: AZD 9668 | AZD-9668 | AZD9668 | KB-105160
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: AZD9668 is a potent, selective and reversible inhibitor of human neutrophil elastase. It was developed as having the potential to be effective for neutrophil-driven inflammatory lung diseases, such as bronchiectasis and COPD [2]. Since the phase II studies did not show clear efficacy for COPD this compound is now listed in the AstraZeneca Open Innovation Clinical Compound Bank for repurposing proposals.

There is ambiguity on PubChem in the assigned nomenclature and stuctures for this compound, as CID 71587812 has been incorrectly assigned alvelestat as a synonym.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 123.81
Molecular weight 545.13
XLogP 4.52
No. Lipinski's rules broken 0
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Canonical SMILES O=C(c1cc(c(n(c1=O)c1cccc(c1)C(F)(F)F)C)c1ccnn1C)NCc1ccc(cn1)S(=O)(=O)C
Isomeric SMILES O=C(c1cc(c(n(c1=O)c1cccc(c1)C(F)(F)F)C)c1ccnn1C)NCc1ccc(cn1)S(=O)(=O)C
InChI InChI=1S/C25H22F3N5O4S/c1-15-20(22-9-10-31-32(22)2)12-21(23(34)30-13-17-7-8-19(14-29-17)38(3,36)37)24(35)33(15)18-6-4-5-16(11-18)25(26,27)28/h4-12,14H,13H2,1-3H3,(H,30,34)
Bioactivity Comments
In contrast with ONO6818, an inhibitor that binds covalently to NE, AZD9668 exhibited a more rapid association and dissociation rate, and its interaction with NE was fully reversible. It also generally showed greater specificity than ONO6818 or sivelestat for NE over other neutrophil-derived serine proteases, particularly Pr-3 and pancreatic elastase [2]. Approximately 90 analogues are listed in a patent [1] where this is example 94, but only limited SAR data is included.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
elastase, neutrophil expressed Primary target of this compound Hs Inhibitor Inhibition 8.0 pKi - 2
pKi 8.0 (Ki 9.4x10-9 M) [2]