Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists.
ACS chemical neuroscience March 19, 2014 Martin Hansen, Karina Phonekeo, James S Paine et al. 125 citations
Adding a benzyl group to the nitrogen atom of phenethylamine psychedelics like 2C-B greatly increases their binding and activity at serotonin 5-HT2A receptors. A library of 48 compounds with varied phenethylamine and N-benzyl structures was tested. Most had high 5-HT2A affinity; compound 8b showed the highest affinity at 0.29 nM, while 1b was the most functionally potent at 0.074 nM. Selectivity over the related 5-HT2C receptor ranged from 1- to 40-fold in binding, though 6b achieved 100-fold selectivity. Functional selectivity was higher, with 1b exceeding 400-fold selectivity for 5-HT2A.