Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6 receptors

Despite possessing a common tryptaminergic scaffold, examination of 28 (i.e., 14 pairs of) compounds suggests that N1-unsubstituted and N1-benzenesulfonyltryptamines likely bind at h5-HT6 receptors in a dissimilar manner (r2 = 0.201). Additionally, an examination of two rotationally constrained N1-benzenesulfonyltryptamine analogs indicates that a non-coplanar relationship between the two aryl groups might be preferred for interaction with the receptors.

Graphical abstractComparative analysis indicates that N1-unsubstituted- and N1-benzenesulfonyltryptamines bind differently at 5-HT6 receptors. Additionally, evaluation of conformationally constrained analogs suggests that a non-coplanar benzenesulfonyl moiety may be optimal for binding.Figure optionsDownload full-size imageDownload as PowerPoint slide