2-Bromomelatonin: synthesis and characterization of a potent melatonin agonist.
A practical synthesis of N-[2-(2-bromo-5-methoxy-1H-indol-3-yl)ethyl]- acetamide (2-bromomelatonin) was achieved by direct bromination of melatonin with N-bromosuccinimide (NBS) in anhydrous acetic acid at room temperature under nitrogen, followed by flash-chromatography. 1H-NMR and mass spectra showed the bromine to be incorporated at the C-2 position of the indole moiety. Tests performed in vitro with isolated melatonin receptors from rabbit parietal cortex demonstrated that the relative binding affinity of 2-bromomelatonin was about ten times higher than that of melatonin and close to that of 2-iodomelatonin. 2-Bromomelatonin behaved as a potent agonist in the physiological studies. It showed enhanced activity in inhibiting the spontaneous firing activity of cortical neurons and similarly to melatonin and 2-iodomelatonin potentiated significantly the inhibitory effect of GABA. 2-Bromomelatonin was also an extremely effective agonist in the tests performed in vivo in the Syrian hamster gonadal regression model.
Duranti
E
E
Institute of Medicinal Chemistry, University of Urbino, Italy.
Stankov
B
B
Spadoni
G
G
Duranti
A
A
Lucini
V
V
Capsoni
S
S
Biella
G
G
Fraschini
F
F
D000818:Animals; D001974:Bromosuccinimide / Q000737:chemistry; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008550:Melatonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008647:Mesocricetus; D009474:Neurons / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; C075920:2-bromomelatonin; D005680:gamma-Aminobutyric Acid; D008550:Melatonin; D001974:Bromosuccinimide