Benzoyl and/or benzyl substituted 1,2,3-triazoles as potassium channel activators. VIII

被引:45
作者
Calderone, V
Giorgi, I
Livi, O
Martinotti, E
Mantuano, E
Martelli, A
Nardi, A
机构
[1] Univ Pisa, Dipartimento Sci Farmaceut, Fac Farm, I-56126 Pisa, Italy
[2] Univ Pisa, Dipartimento Psichiatria Neurobiol Farmacol & Bio, Fac Farm, I-56126 Pisa, Italy
关键词
potassium channels; potassium channel openers; BK-activators; 1,2.3-triazoles; vasodilator activity;
D O I
10.1016/j.ejmech.2005.01.010
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
This paper reports the preparation of new benzoyl and/or benzyl substituted 1,2,3-triazole derivatives and their pharmacological evaluation as potential BK channel openers, as a part of a research program which hypothesized a pharmacophoric structure containing the 1,2,3-triazole ring. The synthetic procedures consist essentially with the 1,3-dipolar cycloaddition of aryl or benzyl azides to the asymmetric alkyne benzoylacetylene to give the wished 4-benzoyl-1,2,3-triazole isomers in larger amount. The pharmacological results show that the 1-(2hydroxybenzyl)-4-benzl-1-1H-1,2,3-triazole possesses high vasorelaxing activity involving the opening of the BK channels. Therefore the structure-activity relationships concerning this pharmacophoi c structure confirm the usefulness of a phenolic function in the ortho position of the aromatic ring and would suggest a 1,2,3-triazole model hearing benzyl substituents. In addition such substituents appear more flexible and able to take different conformations with respect to phenyl groups which have higher trend to coplanar conformations. (c) 2005 Elsevier SAS. All rights reserved.
引用
收藏
页码:521 / 528
页数:8
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