Synthesis and evaluation of dimeric derivatives of 5-HT 2A receptor (5-HT 2AR) antagonist M-100907

Matthew J. Shashack, Kathryn A. Cunningham, Patricia K. Seitz, Andrew McGinnis, Thressa D. Smith, Cheryl S. Watson, Scott R. Gilbertson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

It is now well accepted that at least some serotonin receptors exist in dimeric and oligmeric forms. The linking of receptor ligands has been shown to have potential in the development of selective agonists and antagonists for traditionally refractive receptors. Here we report the development of a dimeric version of the known 5-HT 2AR antagonist, M-100907. Derivatives of M-100907 were synthesized to determine an appropriate site for the linker connection. Then, homodimers with polyether linkers of different lengths were functionally tested in a bioassay to determine the optimal linker length. Attachment at the catechol of M-100907 with linkers between 12 and 18 atoms in length proved to be optimal.

Original languageEnglish (US)
Pages (from-to)640-644
Number of pages5
JournalACS chemical neuroscience
Volume2
Issue number11
DOIs
StatePublished - Nov 16 2011

Keywords

  • 5-HT2AR
  • Serotonin
  • addiction
  • antagonist
  • dimers

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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    Shashack, M. J., Cunningham, K. A., Seitz, P. K., McGinnis, A., Smith, T. D., Watson, C. S., & Gilbertson, S. R. (2011). Synthesis and evaluation of dimeric derivatives of 5-HT 2A receptor (5-HT 2AR) antagonist M-100907. ACS chemical neuroscience, 2(11), 640-644. https://doi.org/10.1021/cn200077q