The impact of radiochemistry in drug projects: The use of C-14 label in the AZD8529, AZD7325, and AZD6280 projects.
GABAAa2,3 allosteric modulator
QWBA
dipeptidyl peptidase 1
mGluR2 positive allosteric modulator
metabolism
Journal
Journal of labelled compounds & radiopharmaceuticals
ISSN: 1099-1344
Titre abrégé: J Labelled Comp Radiopharm
Pays: England
ID NLM: 7610510
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
22
10
2020
revised:
09
12
2020
accepted:
10
12
2020
pubmed:
17
12
2020
medline:
12
1
2022
entrez:
16
12
2020
Statut:
ppublish
Résumé
Understanding the metabolic transformations of a potential drug molecule is important to understanding the safety profile of a drug candidate. Liquid chromatography-mass spectrometry is a standard method for detecting metabolites in the drug discovery stage, but this can lead to an incomplete understanding of the molecule's metabolism. In this manuscript, we highlight the role radiolabeling played in determining the metabolism and in quantifying the metabolites of AZD8529, AZD7325, and AZD6280. A quantitative whole-body autoradiography study can detect covalent adducts in vivo as was the case with AZD5248 in which the compound was bound to the aorta. Ultimately another compound free of aortic binding was developed, AZD7986.
Substances chimiques
4-amino-8-(2,5-dimethoxyphenyl)-N-propylcinnoline-3-carboxamide
0
4-amino-8-(2-fluoro-6-methoxy-phenyl)-N-propylcinnoline-3-carboxamide
0
AZD8529
0
Carbon Radioisotopes
0
Heterocyclic Compounds, 2-Ring
0
Indoles
0
Oxadiazoles
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-72Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
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