Synthesis and biological evaluation of 2-Indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent

Qun Li*, Keith W. Woods, Akiyo Claiborne, Stephen L. Gwaltney,, Kenneth J. Barr, Gang Liu, Laura Gehrke, R. Bruce Credo, Yu Hua Hui, Jang Lee, Robert B. Warner, Peter Kovar, Michael A. Nukkala, Nicolette A. Zielinski, Stephen K. Tahir, Michael Fitzgerald, Ki H. Kim, Kennan Marsh, David Frost, Shi Chung NgSaul Rosenberg, Hing L. Sham

*Corresponding author for this work

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described.

Original languageEnglish (US)
Pages (from-to)465-469
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume12
Issue number3
DOIs
StatePublished - Feb 11 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Li, Q., Woods, K. W., Claiborne, A., Gwaltney, S. L., Barr, K. J., Liu, G., Gehrke, L., Credo, R. B., Hui, Y. H., Lee, J., Warner, R. B., Kovar, P., Nukkala, M. A., Zielinski, N. A., Tahir, S. K., Fitzgerald, M., Kim, K. H., Marsh, K., Frost, D., ... Sham, H. L. (2002). Synthesis and biological evaluation of 2-Indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent. Bioorganic and Medicinal Chemistry Letters, 12(3), 465-469. https://doi.org/10.1016/S0960-894X(01)00759-4