Synthesis of dihydrofuroaporphine derivatives: Identification of a potent and selective serotonin 5-HT1A receptor agonist

Zhili Liu, Hai Zhang, Na Ye, Jing Zhang, QianQian Wu, Peihua Sun, Nyong Li, Xuechu Zhen, Ao Zhang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A series of new aporphine analogues were synthesized and pharmacologically evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19) aporphines displayed the highest affinity at the 5-HT1A receptor with Ki values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer (cis-19). [35S]GTPγS function assays on 5-HT1A receptor indicated that aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high efficacy full antagonist and cis-19 was a full agonist. The agonistic property of cis-19 at the 5-HT1A receptor was further confirmed in vitro and in vivo. This compound may be useful as a potential treatment for anxiety.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalJournal of Medicinal Chemistry
Volume53
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Serotonin 5-HT1 Receptor Agonists
Receptor, Serotonin, 5-HT1A
Aporphines
Anxiety
aporphine

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis of dihydrofuroaporphine derivatives : Identification of a potent and selective serotonin 5-HT1A receptor agonist. / Liu, Zhili; Zhang, Hai; Ye, Na; Zhang, Jing; Wu, QianQian; Sun, Peihua; Li, Nyong; Zhen, Xuechu; Zhang, Ao.

In: Journal of Medicinal Chemistry, Vol. 53, No. 3, 2010, p. 1319-1328.

Research output: Contribution to journalArticle

Liu, Zhili ; Zhang, Hai ; Ye, Na ; Zhang, Jing ; Wu, QianQian ; Sun, Peihua ; Li, Nyong ; Zhen, Xuechu ; Zhang, Ao. / Synthesis of dihydrofuroaporphine derivatives : Identification of a potent and selective serotonin 5-HT1A receptor agonist. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 3. pp. 1319-1328.
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AU - Wu, QianQian

AU - Sun, Peihua

AU - Li, Nyong

AU - Zhen, Xuechu

AU - Zhang, Ao

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