Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype.
Administration, Oral
Animals
Antineoplastic Agents
/ administration & dosage
Carbolines
/ administration & dosage
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Development
Drug Screening Assays, Antitumor
Humans
Mammary Neoplasms, Experimental
/ drug therapy
Mice
Molecular Structure
Proteins
/ antagonists & inhibitors
Structure-Activity Relationship
Triple Negative Breast Neoplasms
/ drug therapy
BET
Bromodomain
Cancer
Lipophilic ligand efficiency
Polar surface area
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 2021
01 11 2021
Historique:
received:
29
06
2021
revised:
05
09
2021
accepted:
15
09
2021
pubmed:
25
9
2021
medline:
11
1
2022
entrez:
24
9
2021
Statut:
ppublish
Résumé
We describe our efforts to introduce structural diversity to a previously described triazole-containing N1-carboline series of bromodomain and extra-terminal (BET) inhibitors. N9 carbolines were designed to retain favorable binding interactions that the N1-carbolines possess. A convergent synthetic route enabled modifications to reduce clearance, enhance physicochemical properties, and improve the overall in vitro profile. This work led to the identification of a potent BET inhibitor, (S)-2-{8-fluoro-5-[(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-7-[4-(
Identifiants
pubmed: 34560263
pii: S0960-894X(21)00603-X
doi: 10.1016/j.bmcl.2021.128376
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Carbolines
0
Proteins
0
bromodomain and extra-terminal domain protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
128376Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.