Calderone Vincenzo, Fiamingo Francesca Lidia, Amato Gabriella, Giorgi Irene, Livi Oreste, Martelli Alma, Martinotti Enrica
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, via Bonanno 6, I-56126 Pisa, Italy.
Eur J Med Chem. 2008 Apr;43(4):792-9. doi: 10.1016/j.ejmech.2007.06.005. Epub 2007 Jul 5.
The vasorelaxing effects of exogenous activators of large-conductance calcium-activated potassium channels (BK channels) can furnish the pharmacological rational basis for the treatment of hypertension and/or other diseases related with an impaired contractility of vessels. Since in previous works some benzanilide derivatives showed BK channel-induced vasorelaxing activity, in this paper we have taken into consideration the introduction of methylene spacer(s) between the amide linker and one or both the aromatic substituents, to evaluate the pharmacological effect caused by these lengthenings and to obtain possible useful information about structure-activity relationships. Overall, the main findings of this work suggest that the introduction of one or two methylene group(s) in the amide linker exerts a negative influence on the BK-opening properties, which can be due to an excessive lengthening of the spacer between the two aromatic rings and/or to further degrees of conformational freedom.
大电导钙激活钾通道（BK通道）的外源性激活剂的血管舒张作用可为治疗高血压和/或其他与血管收缩功能受损相关的疾病提供药理学理论基础。由于在先前的研究中，一些苯甲酰苯胺衍生物显示出BK通道诱导的血管舒张活性，因此在本文中，我们考虑了在酰胺连接基与一个或两个芳基取代基之间引入亚甲基间隔基，以评估这些延长所产生的药理作用，并获得有关构效关系的可能有用信息。总体而言，这项工作的主要发现表明，在酰胺连接基中引入一个或两个亚甲基会对BK开放特性产生负面影响，这可能是由于两个芳环之间间隔基的过度延长和/或构象自由度的进一步增加所致。
