Balanced AT1/AT2 receptor antagonists. 4. XR510 and related 5-(3-amidopropanoyl)imidazoles possessing equal affinity for the AT1 and AT2 receptors

J Med Chem. 1995 Jul 21;38(15):2938-45. doi: 10.1021/jm00015a016.

Abstract

The identification of the AT1 and AT2 receptor subtypes has stimulated interest in developing balanced angiotensin II receptor antagonists. A series of 5-(3-amidopropanoyl)imidazoles has been prepared which possess balanced affinity for the AT1 and AT2 receptors. XR510 (1), 1-[[2'-[[(isopentoxycarbonyl)amino]sulfonyl]-3- fluoro(1,1'-biphenyl)-4-yl]methyl]-5-[3-(N-pyridin-3- ylbutanamido)propanoyl]-4-ethyl-2-propyl-1H-imidazole, potassium salt, exhibits subnanomolar affinity for both receptor sites. XR510 is very active in lowering blood pressure in renal hypertensive rats and furosemide-treated dogs following oral administration.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Angiotensin I / metabolism*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Biphenyl Compounds / metabolism*
  • Biphenyl Compounds / pharmacology*
  • Imidazoles / chemical synthesis*
  • Imidazoles / metabolism*
  • Imidazoles / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, Angiotensin / metabolism*
  • Structure-Activity Relationship

Substances

  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Imidazoles
  • Receptors, Angiotensin
  • XR 510
  • Angiotensin I