Synthesis and Cardiotropic Activity of Linear Methoxyphenyltriazaalkanes

Linked biaromatic compounds as cardioprotective agents

“…[ 316 ] First, the authors obtained a group of bis‐alkoxyphenyltriazaalkanes 96 , where alkoxyphenyl groups of various structures were used as aromatic pharmacophores, and a linear azaalkane chain of various lengths containing three nitrogen atoms was used as a linker. [ 317 ] Among the compounds of this series, the best activity was shown by biaromatic compounds containing three methoxy groups at positions 2, 3, and 4 in each of the aromatic rings. The most active compound was arkadine ( ALM‐802 ) with a chain length of 10 bonds.…”

“…The authors found that the structure of aromatic groups was more critical for the presence of activity, while the length of the linker had less influence. [317][318][319] In small doses (1-3 mg/kg iv), ALM-802 prevented the arrhythmias in rats in the models of aconitic, calcium chloride, and reperfusion arrhythmias, and increased the threshold of electrical fibrillation of the rat heart ventricles from 2 to 10 mA. In model experiments reproducing postinfarction CHF, which is formed in rats with anterior transmural MI 90 days after its reproduction, it was shown that ALM-802 exhibits cardioprotective activity: it significantly reduces the size of the left ventricle of the heart and increases its inotropic function.…”

187 Creation of Novel Cardioprotective Agents on the Basis of Linked Biaromatic Pharmacophore

“…Using this model, we have designed and synthesized a group of bis-(alkoxyphenyl)-triazaalkanes. Compounds of this series have shown pronounced cardioprotective properties in in vivo models of arrhythmia and ischemia [1].…”