Synthesis of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation.
In an attempt to search for more potent positive inotropic agents, a series of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides were synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)piperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamide 4e showed the most potent activity with the 5.09+/-0.00% increased stroke volume (milrinone 1.67+/-0.64%) at a concentration of 1x10(-5)M in our in vitro study. The chronotropic effects of those compounds having significant inotropic effects were also evaluated in this work.
Liu
Xue-Kun
XK
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji, Jilin Province, PR China.
Cui
Xun
X
Hong
Lan
L
Sun
Liang-Peng
LP
Quan
Zhe-Shan
ZS
Piao
Hu-Ri
HR
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D010078:Oxazines / Q000737:chemistry; D015363:Quinolones / Q000737:chemistry; D011817:Rabbits; D012015:Reference Standards; D013057:Spectrum Analysis; D013318:Stroke Volume / Q000187:drug effects
D000081:Acetamides; D002316:Cardiotonic Agents; D010078:Oxazines; D015363:Quinolones