Discovery of 4,4-disubstituted quinazolin-2-ones as T-type calcium channel antagonists

James C. Barrow, Kenneth E. Rittle, Thomas S. Reger, Zhi Qiang Yang, Phung Bondiskey, Georgia B. McGaughey, Mark G. Bock, George D. Hartman, Cuyue Tang, Jeanine Ballard, Yuhsin Kuo, Thomayant Prueksaritanont, Cindy E. Nuss, Scott M. Doran, Steven V. Fox, Susan L. Garson, Richard L. Kraus, Yuxing Li, Michael J. Marino, Valerie Kuzmick GraufeldsVictor N. Uebele, John J. Renger

Research output: Contribution to journalArticle

Abstract

A novel series of quinazolinone T-type calcium channel antagonists have been prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 by modifications of the 3- and 4-positions of the quinazolinone ring afforded potent and selective antagonists that displayed in vivo central nervous system efficacy in epilepsy and tremor models, as well as significant effects on rat active wake as measured by electrocorticogram.

Original languageEnglish (US)
Pages (from-to)75-79
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume1
Issue number2
DOIs
StatePublished - May 13 2010
Externally publishedYes

Keywords

  • Quinazolin-2-ones
  • T-type calcium channel
  • calcium channel antagonists
  • electrocorticogram
  • epilepsy
  • tremor

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Barrow, J. C., Rittle, K. E., Reger, T. S., Yang, Z. Q., Bondiskey, P., McGaughey, G. B., Bock, M. G., Hartman, G. D., Tang, C., Ballard, J., Kuo, Y., Prueksaritanont, T., Nuss, C. E., Doran, S. M., Fox, S. V., Garson, S. L., Kraus, R. L., Li, Y., Marino, M. J., ... Renger, J. J. (2010). Discovery of 4,4-disubstituted quinazolin-2-ones as T-type calcium channel antagonists. ACS Medicinal Chemistry Letters, 1(2), 75-79. https://doi.org/10.1021/ml100004r