化学
苯并噻嗪
格列本脲
钾通道
克罗马卡林
超极化(物理学)
血管平滑肌
效力
ATP敏感性钾离子通道
药理学
生物物理学
兴奋剂
生物化学
内科学
立体化学
内分泌学
体外
受体
平滑肌
糖尿病
医学
有机化学
核磁共振波谱
生物
作者
Alma Martelli,Giuseppe Manfroni,Paola Sabbatini,Maria Letizia Barreca,Vincenzo Calderone,Michela Novelli,Stefano Sabatini,Serena Massari,Oriana Tabarrini,Pellegrino Masiello,Vincenzo Calderone,Violetta Cecchetti
摘要
ATP-sensitive potassium (KATP) channels play a prominent role in controlling cardiovascular function. In this paper, a novel series of 4-(1-oxo-2-cyclopentenyl)-1,4-benzothiazine derivatives modified at the C-2, and C-6 positions were synthesized as openers of vascular KATP channels. Most of the tested compounds evoked vasorelaxing effects on rat aortic rings and membrane hyperpolarization in human vascular smooth muscle cells, with potency similar or superior to that of the reference levcromakalim (LCRK). The selective KATP blocker glibenclamide antagonized the above vascular effects, confirming that KATP channels are closely involved in the mechanism of action. The experimental results confirmed the 1,4-benzothiazine nucleus as an optimal scaffold for activators of vascular KATP channels; moreover, the high level of potency exhibited by the 6-acetyl substituted benzothiazine 8, along with the lack of any significant interference with insulin secretion from pancreatic β-cells, paves the way to further develop a new series of potent activators of vascular KATP channels.
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