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Synthesis and structure–activity relationship study of pyrazolo[3,4-d]pyrimidines as tyrosine kinase RET inhibitors.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jun2017, Vol. 27 Issue 11, p2544-2548. 5p. - Publication Year :
- 2017
-
Abstract
- Three series of pyrazolo[3,4- d ]pyrimidine derivatives were synthesized and evaluated as RET kinase inhibitors. Compounds 23a and 23c were identified to show significant activity both in the biochemical and the BaF3/CCDC6-RET cell assays. Compound 23c was found to significantly inhibit RET phosphorylation and down-stream signaling in BaF3/CCDC6-RET cells, confirming its potent cellular RET-targeting profile. Different from other RET inhibitors with equal potency against KDR that associated with severe toxicity, 23c did not show significant KDR-inhibition even at the concentration of 1 μM. These results demonstrated that 23c is a potent and selective RET inhibitor. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 27
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 122911296
- Full Text :
- https://doi.org/10.1016/j.bmcl.2017.03.088