Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
11 Aug 2022
11 Aug 2022
Historique:
entrez:
18
8
2022
pubmed:
19
8
2022
medline:
19
8
2022
Statut:
epublish
Résumé
The DNA-PK complex is activated by double-strand DNA breaks and regulates the non-homologous end-joining repair pathway; thus, targeting DNA-PK by inhibiting the DNA-PK catalytic subunit (DNA-PKcs) is potentially a useful therapeutic approach for oncology. A previously reported series of neutral DNA-PKcs inhibitors were modified to incorporate a basic group, with the rationale that increasing the volume of distribution while maintaining good metabolic stability should increase the half-life. However, adding a basic group introduced hERG activity, and basic compounds with modest hERG activity (IC
Identifiants
pubmed: 35978693
doi: 10.1021/acsmedchemlett.2c00172
pmc: PMC9377022
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1295-1301Informations de copyright
© 2022 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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