Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907

Scott R. Gilbertson, Ying Chu Chen, Claudia A. Soto, Yaxing Yang, Kenner C. Rice, Kathryn Cunningham, Noelle Anastasio

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The approach of tethering together two known receptor ligands, to be used as molecular probes for the study of G protein-coupled receptor (GPCR) systems, has proven to be a valuable approach. Selective ligands that possess functionality that can be used to link to other ligands, are useful in the development of novel antagonists and agonists. Such molecules can also be attached to reporter molecules, such as fluorophores, for the study of GPCR dimerization and its role in signaling. The highly selective serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907 (volinanserin) is of clinical interest in the treatment of neurological and mental health disorders. Here, we synthesized the most active (+)-M100907 enantiomer as well as a series of derivatives that possessed either an alkyne or an azide. The triazole resulting from the dipolar cycloaddition of these groups did not interfere with the ability of the bivalent ligand to act as an antagonist. Thus, we have synthesized a number of compounds which will prove useful in elucidating the role of the 5-HT2AR in the central nervous system.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry Letters
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Serotonin 5-HT2 Receptor Antagonists
Receptor, Serotonin, 5-HT2A
Serotonin
Ligands
Derivatives
G-Protein-Coupled Receptors
Molecular Probes
Molecules
Aptitude
Triazoles
Alkynes
Azides
Cycloaddition
Dimerization
Enantiomers
Fluorophores
Cycloaddition Reaction
Neurology
Mental Disorders
Mental Health

Keywords

  • Bivalent
  • M100907
  • Serotonin
  • Volinanserin

ASJC Scopus subject areas

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

Cite this

Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907. / Gilbertson, Scott R.; Chen, Ying Chu; Soto, Claudia A.; Yang, Yaxing; Rice, Kenner C.; Cunningham, Kathryn; Anastasio, Noelle.

In: Bioorganic and Medicinal Chemistry Letters, 01.01.2018.

Research output: Contribution to journalArticle

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