5-HT6 serotonin receptor binding affinities of N-1-benzenesulfonyl and related tryptamines

N-1-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT, 2; Ki = 2.1 nM) binds at 5-HT6 receptors with enhanced affinity relative to 5-OMe DMT (Ki = 77 nM). The role of the benzenesulfonyl group was examined by rep lacing the sulfoxide portion with a methylene group or a carbonyl group, or by its complete elimination. Several different indole 2- and 5-positions s ubstituents were also explored to a limited degree. Although the effect of N-1 modifications are seemingly dependent upon other substituents present i n the molecule, the N-1-benzenesulfonyl moiety is generally optimal with re spect to affinity enhancement.