The Chemical Development of CHIR-258

Authors

  • Shuguang Zhu
  • Minna Zheng
  • Brian Diaz
  • Arthur Yeung
  • Li Jin
  • Gabriel Galvin
  • Xiao Shang
  • Shaopei Cai
  • Eric Harwood
  • David Ryckman

DOI:

https://doi.org/10.2533/chimia.2006.584

Keywords:

4-amino-5-fluoro-3-[6-(4-methyl-1-piperazinyl)-1h-benzimidazol-2-yl]-2(1h)-quinolinone, Api, Chemical development, Chir-258, Contract manufacturing organization (cmo), In-process control (ipc), Kinase inhibitor, Lactate, Technology transfer, Vascular endothelial growth factor (vegf)

Abstract

This paper is a case history of the early stage chemical development of CHIR-258 (4-amino-5-fluoro-3-[6(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone, DL-lactate salt), a vascular endothelial growth factor (VEGF) kinase inhibitor for treatment of solid and hematologic cancers. The article covers various aspects of work in chemical development. In particular we discuss evaluation of the medicinal chemistry route, scale-up, salt preparation, process impurities, in-process control (IPC) method development, supply route development, technology transfer to contract manufacturing organization (CMO) and pilot plant production. Some interesting points regarding regulatory requirement for chemical development are also discussed.

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Published

2006-09-01

Issue

Vol. 60 No. 9 (2006): Process Chemistry

Section

Scientific Articles

License

Copyright (c) 2006 Swiss Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

[1]
S. Zhu, M. Zheng, B. Diaz, A. Yeung, L. Jin, G. Galvin, X. Shang, S. Cai, E. Harwood, D. Ryckman, Chimia 2006, 60, 584, DOI: 10.2533/chimia.2006.584.