Synthesis of 2-(4-substituted benzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation.
Herein we describe the discovery of compound 3g, a potent positive inotropic agent compared with the standard drug, milrinone. Compound 3g was developed from a series of 2-(4-substitutedbenzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl) acetamides found in an evaluation of inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities, but 3g was the most potent, with 7.68+/-0.14% increased stroke volume (milrinone 2.38+/-0.05%) at 1 x 10(-5)M in our in vitro study. The chronotropic effects of compounds having significant inotropic effects were also evaluated.
Yang
Kun
K
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, PR China.
Sun
Liang-Peng
LP
Liu
Ji-Yong
JY
Cui
Xun
X
Piao
Hu-Ri
HR
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000737:chemistry*; D048588:Benzoxazines / Q000737:chemistry*; D001593:Benzyl Compounds / Q000737:chemistry*; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006325:Heart Atria / Q000503:physiopathology; D020105:Milrinone / Q000494:pharmacology; D011817:Rabbits
C545228:1,4-diazepane; D000081:Acetamides; D001381:Azepines; D048588:Benzoxazines; D001593:Benzyl Compounds; D002316:Cardiotonic Agents; D020105:Milrinone