Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2

Guangrong Zheng, Linda P. Dwoskin, Agripina G. Deaciuc, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A series of lobelane homologues has been synthesized and evaluated for their [3H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.

Original languageEnglish
Pages (from-to)6509-6512
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number24
DOIs
StatePublished - Dec 15 2008

Bibliographical note

Funding Information:
This research was supported by NIH Grant DA 13519.

Keywords

  • Lobelane
  • Structure-activity relationship
  • Vesicular monoamine transporter

ASJC Scopus subject areas

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

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