Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist - PubMed (original) (raw)

. 2004 Nov 18;47(24):5995-6008.

doi: 10.1021/jm049715t.

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

Affiliations

• PMID: 15537354
• DOI: 10.1021/jm049715t

Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist

Yiqian Wan et al. J Med Chem. 2004.

Abstract

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 K(i) > 10 microM 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.

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