Synthesis and structure-activity relationships of novel, substituted 5,6-dihydrodibenzo[a,g]quinolizinium P2X7 antagonists

Ga Eun Lee, Ho Sung Lee, So Deok Lee, Jung Ho Kim, Won Ki Kim, Yong Chul Kim

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X7 antagonists. To assess their structure-activity relationships, these compounds were modified at their R1 and R2 groups and assayed for their ability to inhibit the 2′(3′)-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluorescent ethidium by HEK-293 cells stably expressing the human P2X7 receptor, and their ability to inhibit BzATP-induced IL-1β release by differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R1 position, and especially compound 19h, with the 2-NO2-4,5-dimethoxy-benzyl group at the R2 position, had potent inhibitory efficacy as P2X7 antagonists.

Original languageEnglish
Pages (from-to)954-958
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number3
Publication statusPublished - 2009 Feb 1

Bibliographical note

Funding Information:
This study was supported by a grant of the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720430) and by a research grant from the Korea Science and Engineering Foundation (R01-2006-000-10880-0).


  • Antagonist
  • Ethidium uptake
  • Human P2X receptor
  • IL-1β release
  • Iminium quaternary protoberberine alkaloids

ASJC Scopus subject areas

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


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