Synthesis of 5-Substituted-1H-indol-2-yl-1H-quinolin-2-ones: A Novel Class of KDR Kinase Inhibitors
- 25 February 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 70 (7), 2555-2567
- https://doi.org/10.1021/jo0480545
Abstract
[reaction: see text] A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.Keywords
This publication has 81 references indexed in Scilit:
- Property-Based Design of KDR Kinase InhibitorsCurrent Medicinal Chemistry, 2004
- Rapid and Efficient Synthesis of 1H-Indol-2-yl-1H-quinolin-2-onesOrganic Letters, 2003
- Tyrosine kinases as targets in cancer therapy – successes and failuresEmerging Therapeutic Targets, 2003
- Angiogenesis in cancer and other diseasesNature, 2000
- Application of the Pd-catalyzed heteroarylation to the synthesis of 5-(indol-2′-yl)pyridin-2-one and 5-(indol-2′-yl)pyran-2-oneTetrahedron, 1998
- Palladium(0)-Catalysed Arylations using Pyrrole and Indole 2-Boronic AcidsSynlett, 1998
- Angiogenesis and Tumor MetastasisAnnual Review of Medicine, 1998
- Vascular Endothelial Growth Factor, a Potent and Selective Angiogenic AgentOnline Journal of Public Health Informatics, 1996
- Clinical Applications of Research on AngiogenesisThe New England Journal of Medicine, 1995
- Angiogenesis in cancer, vascular, rheumatoid and other diseaseNature Medicine, 1995