Synthesis of novel 1,4-benzoxazin-3-one derivatives as inhibitors against tyrosine kinases

Takahiro Honda; Takahiro Terao; Hiroyuki Aono; Masakazu Ban

doi:10.1016/j.bmc.2008.11.060

Synthesis of novel 1,4-benzoxazin-3-one derivatives as inhibitors against tyrosine kinases

Bioorg Med Chem. 2009 Jan 15;17(2):699-708. doi: 10.1016/j.bmc.2008.11.060. Epub 2008 Dec 6.

Authors

Takahiro Honda¹, Takahiro Terao, Hiroyuki Aono, Masakazu Ban

Affiliation

¹ Research and Development Center, Santen Pharmaceutical Co. Ltd, 8916-16 Takayama-cho, Ikoma-shi, Nara 630-0101, Japan. hondat@ms.naist.jp

PMID: 19109024
DOI: 10.1016/j.bmc.2008.11.060

Abstract

We designed and synthesized a novel 1,4-benzoxazin-3-one derivative 4 which would have inhibitory activities against tyrosine kinases. They could be synthesized easily from various carboxylic acids 10 and commercially available amines using TFP resin without purification. In this article, we will report the design and synthesis of a novel 1,4-benzoxazin-3-one chemical library 4 and the inhibitory activities against KDR and ABL which are closely related to chronic diseases such as cancer.

MeSH terms

Amines
Benzoxazines / chemical synthesis*
Benzoxazines / pharmacology
Carboxylic Acids
Drug Design
Protein-Tyrosine Kinases / antagonists & inhibitors*
Proto-Oncogene Proteins c-abl / antagonists & inhibitors
Small Molecule Libraries / chemical synthesis
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

Amines
Benzoxazines
Carboxylic Acids
Small Molecule Libraries
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor Receptor-2
Proto-Oncogene Proteins c-abl