Synthesis of 2-(4-substitutedbenzyl-[1,4]diazepan-1-yl)-n-(1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides as inotropic agents.
In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide (6m) was the most potent, increasing stroke volume by 8.38±0.16% (milrinone 2.45± 0.06%) at 3 x 10(-5) m. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
Key Laboratory of Natural Resources of Changbai Mountains & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China.
Bai-Jun
BJ
Ye
Xue-Kun
XK
Liu
Sheng-Ming
SM
Jiang
Xun
X
Cui
Hu-Ri
HR
Piao
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D020105:Milrinone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009924:Organ Culture Techniques / Q000379:methods; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects*; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
C558591:2-(4-(4-methylbenzyl)-(1,4)diazepan-1-yl)-N-(4,5-dihydro-1-methyl-(1,2,4)triazolo(4,3-a)quinolin-7-yl)acetamide; D000081:Acetamides; D001381:Azepines; D002316:Cardiotonic Agents; D014230:Triazoles; D020105:Milrinone