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- Wan, Y., et al.
(författare)
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Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist
- 2004
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Ingår i: J Med Chem. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:24, s. 5995-6008
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Tidskriftsartikel (refereegranskat)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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