NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS .1. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF PYRIDINE-DERIVATIVES

Substituted pyridines were synthesized as potential angiotensin II (AI I) receptor antagonists. Substitution at the position 2 in the pyridin e resulted in potent activity, and the optimal alkyl length was four c arbons. The potency further increased with the introduction of a hydro xymethyl group at the position 4. One of the compounds, [2'(1H-tetrazo l-5-yl)biphenyl-4-yl]methyl]pyridine 9 h (KT3-579) is a competitive AI I antagonist with a pA(2) value of 9.31, and is about 10 times more po tent than Du Pont 753. It was found to be an AT(1) specific antagonist with an IC50 of 3.09 nM.