Design, synthesis, and biological evaluation, of the first selective nonpeptide AT 2 receptor agonist

Yiqian Wan, Charlotta Wallinder, Bianca Plouffe, Hélène Beaudry, A. K. Mahalingam, Xiongyu Wu, Berndt Johansson, Mathias Holm, Milad Botoros, Anders Karlén, Anders Pettersson, Fred Nyberg, Lars Fändriks, Nicole Gallo-Payet*, Anders Hallberg, Mathias Alterman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

256 Citations (Scopus)


The first druglike selective angiotensin II AT 2 receptor agonist (21) with a K i value of 0.4 nM for the AT 2 receptor and a Ki > 10 μM for the AT 1 receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44 mapk , enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT 2 receptor. Compound 21, derived from the prototype nonselective AT 1 /AT 2 receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT 2 receptor in more detail.

Original languageEnglish
Pages (from-to)5995-6008
Number of pages14
JournalJournal of Medicinal Chemistry
Issue number24
Publication statusPublished - 18 Nov 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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