Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT).
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:
14 Nov 2019
14 Nov 2019
Historique:
received:
19
07
2019
accepted:
10
10
2019
entrez:
22
11
2019
pubmed:
22
11
2019
medline:
22
11
2019
Statut:
epublish
Résumé
Small molecules that inhibit the metabolic enzyme NAMPT have emerged as potential therapeutics in oncology. As part of our effort in this area, we took a scaffold morphing approach and identified 3-pyridyl azetidine ureas as a potent NAMPT inhibiting motif. We explored the SAR of this series, including 5 and 6 amino pyridines, using a convergent synthetic strategy. This lead optimization campaign yielded multiple compounds with excellent in vitro potency and good ADME properties that culminated in compound
Identifiants
pubmed: 31749905
doi: 10.1021/acsmedchemlett.9b00325
pmc: PMC6862340
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1524-1529Informations de copyright
Copyright © 2019 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare the following competing financial interest(s): The authors were all employees of the Novartis Institutes for Biomedical Research during the time when this work was completed.
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