Indazolylpyrazolopyrimidine as Highly Potent B-Raf Inhibitors with in Vivo Activity

Novel indazolylpyrazolo[1,5-a]pyrimidine analogues have been prepared and found to be extremely potent type I B-Raf inhibitors. The lead compound shows good selectivity against a panel of 60 kinases, possesses a desirable pharmacokinetic profile, and demonstrates excellent in vivo antitumor efficacy...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2010-11, Vol.53 (21), p.7874-7878
Main Authors: Wang, Xiaolun, Berger, Dan M, Salaski, Edward J, Torres, Nancy, Dutia, Minu, Hanna, Cilien, Hu, Yongbo, Levin, Jeremy I, Powell, Dennis, Wojciechowicz, Donald, Collins, Karen, Frommer, Eileen, Lucas, Judy
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis
Bridged Bicyclo Compounds, Heterocyclic - chemistry
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Indazoles - chemical synthesis
Indazoles - chemistry
Indazoles - pharmacology
Mice
Models, Molecular
Mutation
Neoplasm Transplantation
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
Pyrazoles - chemical synthesis
Pyrazoles - chemistry
Pyrazoles - pharmacology
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Structure-Activity Relationship
Transplantation, Heterologous
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Novel indazolylpyrazolo[1,5-a]pyrimidine analogues have been prepared and found to be extremely potent type I B-Raf inhibitors. The lead compound shows good selectivity against a panel of 60 kinases, possesses a desirable pharmacokinetic profile, and demonstrates excellent in vivo antitumor efficacy in B-Raf mutant xenograft models.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm1007566