Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine, a potent cyclin dependent kinase 1 (CDK1) inhibitor

Shenlin Huang; Ronghui Lin; Yang Yu; Yanhua Lu; Peter J Connolly; George Chiu; Shengjian Li; Stuart L Emanuel; Steven A Middleton

doi:10.1016/j.bmcl.2006.12.031

Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine, a potent cyclin dependent kinase 1 (CDK1) inhibitor

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1243-5. doi: 10.1016/j.bmcl.2006.12.031. Epub 2006 Dec 15.

Authors

Shenlin Huang¹, Ronghui Lin, Yang Yu, Yanhua Lu, Peter J Connolly, George Chiu, Shengjian Li, Stuart L Emanuel, Steven A Middleton

Affiliation

¹ Johnson & Johnson Pharmaceutical Research & Development L. L. C., 1000 Route 202, Raritan, NJ 08869, USA. shenlinhuang@hotmail.com

PMID: 17234412
DOI: 10.1016/j.bmcl.2006.12.031

Abstract

The novel compound 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine was discovered to be a potent CDK1 inhibitor. Described here is the chemistry for its synthesis, including Pd(II) catalyzed Stille coupling reaction and sulfur(0) induced benzimidazole formation. Its effects on VEGFR-2 kinase activity and tumour cell proliferation are also described.

MeSH terms

Benzimidazoles
CDC2 Protein Kinase / antagonists & inhibitors*
Catalysis
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Isoquinolines / chemical synthesis
Isoquinolines / pharmacology
Palladium
Pyridines / chemical synthesis*
Pyridines / pharmacology*
Structure-Activity Relationship
Sulfur
Vascular Endothelial Growth Factor Receptor-2 / drug effects

Substances

3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo(1,2-b)pyridine
Benzimidazoles
Isoquinolines
Pyridines
Palladium
Sulfur
benzimidazole
Vascular Endothelial Growth Factor Receptor-2
CDC2 Protein Kinase