Synthesis and positive inotropic evaluation of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)-acetamides.
In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 +/- 0.18% increased stroke volume (Milrinone: 1.67 +/- 0.64%) at a concentration of 1 x 10(-5) M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
Li
Jing-Yuan
JY
Key Laboratory of Natural Resources and Functional Molecules of Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji, Jilin, PR China.
Cui
Xun
X
Liu
Xue-Kun
XK
Hong
Lan
L
Quan
Zhe-Shan
ZS
Piao
Hu-Ri
HR
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects
D000081:Acetamides; D002316:Cardiotonic Agents; D011804:Quinolines