Research of potential antidepressant drugs with α2-adrenoreceptor antagonist and NA-uptake inhibiting properties: synthesis of 2-(1-hydroxy-2-phenoxy-2-phenyl)ethyl-4,5-dihydro-1H-imidazole derivatives
作者:P Dostert、P Melloni、A Della Torre、M Varasi、L Merlini、A Bonsignori、S Ricciardi
DOI:10.1016/0223-5234(90)90195-9
日期:1990.11
A series of 2-(1-hydroxy-2-phenoxy-2-phenyl)ethyl-4,5-dihydro-1H-imidazole derivatives has been synthesized with the aim of finding potential antidepressant drugs endowed with both NA-uptake and alpha-2-antagonist properties. The structure of the new compounds was designed by mixing the common elements present in reboxetine and alpha-aryloxy-benzyl derivatives of ethanolamine, both having NA-uptake inhibitory properties in vitro, and in idazoxan, a potent and selective alpha-2-adrenoreceptor antagonist. The new hybrids allow a good fitting of the common features without the strong steric interactions occurring when the structure of reboxetine is superimposed on that of idazoxan. However, the new derivatives did not display significant interaction with the NA-uptake system and the alpha-2-adrenoreceptors and proved inactive in the antireserpine test taken as a model of potential antidepressant activity. The possible relationship between the structural changes made in the parent molecules and the complete loss of activity on both systems is discussed.