Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
Eur J Med Chem. 2015 Jan 27;90:822-33. doi: 10.1016/j.ejmech.2014.12.021. Epub 2014 Dec 13.
In this paper we report the investigation of C-3 and β-acetamide positions of agomelatine analogues. Concomitant insertion of a hydroxymethyl in the β-acetamide position and aliphatic groups in C-3 position produced a positive effect on both melatonin (MT1, MT2) and serotonin (5-HT2C) binding affinities. In particular, the allyl 6b and ethyl 15a represented the more interesting compounds of this series. Furthermore, the introduction of methyl cycloalkyl groups (compounds 11a, 12a) exhibited no change in both MT2 and 5-HT2C binding affinities while a decrease of MT1 binding affinity occurred leading to an MT2 selectivity. Finally, the acetamide modulation has led to methyl thiourea 11h, with a weak MT2 selectivity.
在本文中，我们报告了对阿莫曲坦类似物的 C-3 位和β-乙酰胺位置的研究。β-乙酰胺位置同时插入羟甲基和 C-3 位的脂肪族基团对褪黑素（MT1、MT2）和血清素（5-HT2C）结合亲和力都产生了积极的影响。特别是丙烯基 6b 和乙基 15a 是该系列中更有趣的化合物。此外，引入甲基环烷基（化合物 11a、12a）对 MT2 和 5-HT2C 结合亲和力没有变化，而 MT1 结合亲和力降低导致 MT2 选择性。最后，乙酰胺的调节导致了具有弱 MT2 选择性的甲基硫脲 11h。
