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Medicinal chemistry approaches to avoid aldehyde oxidase metabolism.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Apr 15; Vol. 22 (8), pp. 2856-60. Date of Electronic Publication: 2012 Mar 03. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aldehyde Oxidase antagonists & inhibitors
Aldehyde Oxidase chemistry
Animals
Cells, Cultured
Chemistry, Pharmaceutical
Cytosol enzymology
Dogs
Drug Stability
Humans
Male
Pyridines chemistry
Rats
Structure-Activity Relationship
Toll-Like Receptor 7 agonists
Aldehyde Oxidase metabolism
Pyridines chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 22
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 22429467
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.02.069