Synthesis and Evaluation of Imidazo[1,2-a]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3-Kinase Inhibitors.
biological activity
cross-coupling
hydrogen bonds
inhibitors
kinases
scaffold hopping
Journal
Chemistry, an Asian journal
ISSN: 1861-471X
Titre abrégé: Chem Asian J
Pays: Germany
ID NLM: 101294643
Informations de publication
Date de publication:
15 Apr 2019
15 Apr 2019
Historique:
received:
02
12
2018
revised:
13
01
2019
pubmed:
5
2
2019
medline:
30
4
2019
entrez:
5
2
2019
Statut:
ppublish
Résumé
Using a scaffold-hopping approach, imidazo[1,2-a]pyridine analogues of the ZSTK474 (benzimidazole) class of phosphatidylinositol 3-kinase (PI3K) inhibitors have been synthesized for biological evaluation. Compounds were prepared using a heteroaryl Heck reaction procedure, involving the palladium-catalysed coupling of 2-(difluoromethyl)imidazo[1,2-a]pyridines with chloro, iodo or trifluoromethanesulfonyloxy (trifloxy) substituted 1,3,5-triazines or pyrimidines, with the iodo intermediates being preferred in terms of higher yields and milder reaction conditions. The new compounds maintain the PI3K isoform selectivity of their benzimidazole analogues, but in general show less potency.
Identifiants
pubmed: 30714356
doi: 10.1002/asia.201801762
doi:
Substances chimiques
Enzyme Inhibitors
0
Phosphoinositide-3 Kinase Inhibitors
0
Pyridines
0
imidazo(1,2-a)pyridine
G18ZBV2HXA
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1249-1261Subventions
Organisme : Health Research Council of New Zealand
ID : 06/062; 09/388; 12/220; 13/376
Organisme : Maurice Wilkins Centre for Molecular Biodiscovery
Organisme : Pathway Therapeutics Inc.
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.