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2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Jan 15; Vol. 20 (2), pp. 679-83. Date of Electronic Publication: 2009 Nov 20. - Publication Year :
- 2010
-
Abstract
- A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3beta phosphorylation in a BT474 tumor xenograft model in mice.<br /> (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Glycogen Synthase Kinase 3 antagonists & inhibitors
Glycogen Synthase Kinase 3 metabolism
Glycogen Synthase Kinase 3 beta
Humans
Indazoles chemical synthesis
Indazoles pharmacology
Mice
Phosphorylation
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins c-akt metabolism
Pyrazines chemical synthesis
Pyrazines pharmacology
Pyridines chemical synthesis
Pyridines pharmacology
Xenograft Model Antitumor Assays
Indazoles chemistry
Protein Kinase Inhibitors chemistry
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Pyrazines chemistry
Pyridines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 20005102
- Full Text :
- https://doi.org/10.1016/j.bmcl.2009.11.060