138335-03-2Relevant academic research and scientific papers
Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site
Kimball,Floyd,Das,Hunt,Krapcho,Rovnyak,Duff,Lee,Moquin,Turk,Hedberg,Moreland,Brittain,McMullen,Normandin,Cucinotta
, p. 780 - 793 (2007/10/02)
We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presenc
Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones
Floyd,Kimball,Krapcho,Das,Turk,Moquin,Lago,Duff,Lee,White,Ridgewell,Moreland,Brittain,Normandin,Hedberg,Cucinotta
, p. 756 - 772 (2007/10/02)
As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).
