Balanced AT1/AT2 Receptor Antagonists. 4. XR510 and Related 5-(3-Amidopropanoyl)imidazoles Possessing Equal Affinity for the AT1 and AT2 Receptors

The identification of the AT(1) and AT(2) 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 AT(1) and AT(2) 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.