bis-Pyridinium cyclophanes: Novel ligands with high affinity for the blood-brain barrier choline transporter

Zhenfa Zhang, Paul R. Lockman, Rajendar K. Mittapalli, David D. Allen, Linda P. Dwoskin, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


A series of bis-pyridinium cyclophane analogs designed as conformationally restricted bis-quaternary ammonium compounds were evaluated for their affinity for the blood-brain barrier (BBB) choline transporter. All the cyclophanes investigated exhibited high affinity compared to choline. Of these compounds, N, N′-(1,10-decanediyl)3,3′-(1,9-decadiyn-1,10-diyl)-bis-pyridinium diiodide (5c) and N,N′-(1,9-nonanediyl)3,3′-(1,9-decadiyn-1,10-diyl)-bis-pyridinium dibromide (5b) exhibited highest affinity with Ki values of 0.8 μM and 1.4 μM, respectively, and constitute some of the most potent BBB choline transporter ligands reported.

Original languageEnglish
Pages (from-to)5622-5625
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number20
StatePublished - Oct 15 2008

Bibliographical note

Funding Information:
This work was supported by National Institute of Health Grant U19 DA017548.


  • Blood-brain barrier choline transporter
  • Nicotinic acetylcholine receptor
  • Quaternary ammonium

ASJC Scopus subject areas

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


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