Identification of 5H-chromeno[3,4-c]pyridine and 6H-isochromeno[3,4-c]pyridine derivatives as potent and selective dual ROCK inhibitors.
Chromenopyridine
Chromenopyrimidine
ROCK inhibitor
Rho kinase
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
received:
10
07
2020
accepted:
04
08
2020
pubmed:
18
8
2020
medline:
23
6
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
A novel series of 5H-chromeno[3,4-c]pyridine, 6H-isochromeno[3,4-c]pyridine and 6H-isochromeno[4,3-d]pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC
Identifiants
pubmed: 32805407
pii: S0960-894X(20)30585-0
doi: 10.1016/j.bmcl.2020.127474
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Pyridines
0
ROCK1 protein, human
EC 2.7.11.1
ROCK2 protein, human
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127474Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.