Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1361289 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
Abstract
Aldehyde oxidase (AO) is a molybdenum-containing enzyme distributed throughout the animal kingdom and capable of metabolising a wide range of aldehydes and N-heterocyclic compounds. Although metabolism by this enzyme in man is recognised to have significant clinical impact where human AO activity was not predicted by screening in preclinical species, there is very little reported literature offering real examples where drug discoverers have successfully designed away from AO oxidation. This article reports on some strategies adopted in the Pfizer TLR7 agonist programme to successfully switch off AO metabolism that was seen principally in the rat.
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Related Topics
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Organic Chemistry
Authors
David C. Pryde, Thien-Duc Tran, Peter Jones, Jonathan Duckworth, Martin Howard, Iain Gardner, Ruth Hyland, Rob Webster, Tracey Wenham, Sharan Bagal, Kiyoyuki Omoto, Richard P. Schneider, Jian Lin,