TY - JOUR
T1 - Research of potential antidepressant drugs with α2-adrenoreceptor antagonist and NA-uptake inhibiting properties
T2 - synthesis of 2-(1-hydroxy-2-phenoxy-2-phenyl)ethyl-4,5-dihydro-1H-imidazole derivatives
AU - Dostert, P.
AU - Melloni, P.
AU - Della Torre, A.
AU - Varasi, M.
AU - Merlini, L.
AU - Bonsignori, A.
AU - Ricciardi, S.
PY - 1990
Y1 - 1990
N2 - 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 α2-antagonist properties. The structure of the new compounds was designed by mixing the common elements present in reboxetine and α-aryloxy-benzyl derivatives of ethanolamine, both having NA-uptake inhibitory properties in vitro, and in idazoxan, a potent and selective α2-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 α2-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.
AB - 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 α2-antagonist properties. The structure of the new compounds was designed by mixing the common elements present in reboxetine and α-aryloxy-benzyl derivatives of ethanolamine, both having NA-uptake inhibitory properties in vitro, and in idazoxan, a potent and selective α2-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 α2-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.
KW - idazoxan
KW - NA-uptake inhibitors
KW - reboxetine
KW - α-adrenoreceptor antagonists
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U2 - 10.1016/0223-5234(90)90195-9
DO - 10.1016/0223-5234(90)90195-9
M3 - Article
AN - SCOPUS:0025606977
VL - 25
SP - 757
EP - 763
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 9
ER -