1. Novel difluoroacetamide analogues of agomelatine and melatonin: probing the melatonin receptors for MT1 selectivity
Darius P. Zlotos,* Noura M. Riad, Mai B. Osman, Bala R. Dodda and Paula A. Witt-Enderby. Med. Chem. Commun.,2015, 6, 1340–1344
Agomelatine was synthesized according to our previously reported procedure. 5-Methoxytryptamine and N-desacetyl-agomelatine were prepared by amide hydrolysis of melatonin and agomelatine, respectively, using ethanolic KOH. Trifluoroagomelatine was prepared by acylation of using trifluoroacetic anhydride in pyridine as previously reported. Difluoroagomelatine (ref. 14) and dichloroagomelatine were obtained by acylation of using methyl difluoroacetate, and methyl dichloroacetate, respectively (Scheme 1).
2. Iodine salts of the pharmaceutical compound agomelatine: the effect of the symmetric H-bond on amide protonation
Eliška Skořepová,* Michal Hušák, Luděk Ridvan. CrystEngChem.,2016, 18,4518–4529
Since the existence of agomelatine hydrochloride and hydrobromide was described in the patent literature, we attempted to prepare the hydriodide AGI as well. Due to favorable reaction conditions described later, we prepared not only AGI but also three novel and structurally different iodine salts of agomelatine. Here, we present their synthesis and characterization, a comparison of crystal structures and a detailed discussion on the ionization state of the agomelatine molecule.
3. Design, synthesis and biological evaluation of ﬂuorescent ligands for MT1 and/or MT2
G. Viault, S. Poupart, F. Suzenet*. RSC Adv.,2016, 6, 62508–62521
Melatonin (N-acetyl-5-methoxytryptamine, Scheme 1) is a neurohormone synthesized by the pineal gland during the dark period in all animal species and immediately released. The rhythm of melatonin synthesis is directly controlled by photoperiodism. Melatonin secretion both in blood and in cerebrospinal fluid transduces the photoperiodicmessage to all central or peripheral structures expressing melatoninergic receptors or binding sites, allowing synchronization of several cellular and physiological events to a given daylength. Melatonin rhythm synchronizes a wide range of physiological functions including among others circadian rhythms or seasonal reproduction. Anarchic melatonin secretion also accounts for disorders of sleep/wake rhythms associated or not with depression. Melatonin receptors play an important role in the mode of action of a few drugs such as ramelteon (Rozerem®), a melatonin agonist, employed to treat insomnia and nocturia and agomelatine (Valdoxan®), a melatonin agonist and 5-HT2C antagonist, indicated for the treatment of depression.