Geoffrey B Varty, Clinton E Canal, Tina A Mueller, Joshua A Hartsel, Richa Tyagi, Ken Avery, Michael E Morgan, Amy C Reichelt, Pradip Pathare, Erik Stang, Michael G Palfreyman, Alex Nivorozhkin
Structure-activity studies of 4-substituted-2,5-dimethoxyphenethylamines led to the discovery of 2,5-dimethoxy-4-thiotrifluoromethylphenethylamines, including CYB210010, a potent and long-acting serotonin 5-HT2 receptor agonist. CYB210010 exhibited high agonist potency at 5-HT2A and 5-HT2C receptors, modest selectivity over 5-HT2B , 5-HT1A , 5-HT6 , and adrenergic α2A receptors, and lacked activity at monoamine transporters and over 70 other proteins. CYB210010 (0.1-3 mg/kg) elicited a head-twitch response (HTR) and could be administered subchronically at threshold doses without behavioral tolerance...
April 9, 2024: Journal of Medicinal Chemistry