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 Watson; Scott R. Gilbertson

doi:10.1021/cn200077q

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 Watson, Scott R. Gilbertson

Pharmacology & Toxicology

Research output: Contribution to journal › Article › peer-review

17 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 language	English (US)
Pages (from-to)	640-644
Number of pages	5
Journal	ACS chemical neuroscience
Volume	2
Issue number	11
DOIs	https://doi.org/10.1021/cn200077q
State	Published - Nov 16 2011

Keywords

5-HT2AR
Serotonin
addiction
antagonist
dimers

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

Access to Document

10.1021/cn200077q

Cite this

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AU - McGinnis, Andrew

AU - Smith, Thressa D.

AU - Watson, Cheryl

AU - Gilbertson, Scott R.

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