Nonpeptide Angiotensin II Receptor Antagonists. I. Synthesis and Biological Activity of Pyridine Derivatives

概要

論文の詳細を見る
Substituted pyridines were synthesized as potential angiotensin II (AII) receptor antagonists. Substitution at the position 2 in the pyridine resulted in potent activity, and the optimal alkyl length was four carbons. The potency further increased with the introduction of a hydroxymethyl group at the position 4. One of the compounds, 2-butyl-6-chloro-4-hydroxymethyl-5-methyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]pyridine 9h (KT3-579) is a competitive AII antagonist with a pA_2 value of 9.31,and is about 10 times more potent than Du Pont 753. It was found to be an AT_1 specific antagonist with an IC_<50> of 3.09nM.
社団法人日本薬学会の論文
1994-09-15