Conformationally restricted homotryptamines. Part 4: Heterocyclic and naphthyl analogs of a potent selective serotonin reuptake inhibitor

A series of hybrid molecules containing the cyclopropylmethylamino side chain found in homotryptamine (1S,2S)-2c and an isosteric heteroaryl or naphthyl core were prepared and their binding affinities for the human serotonin transporter determined. The most potent isosteres were CN-substituted naphthalenes. These results demonstrate that isosteric aromatic cores which lack an H-bond donor site may be substituted for the indole nucleus without substantial loss in hSERT binding.

Graphical abstractHybrid molecules containing the cyclopropylmethylamino side chain found in the parent homotryptamine system and an isosteric heteroaryl or naphthyl core were prepared and their binding affinities for the human serotonin transporter determined.Figure optionsDownload full-size imageDownload as PowerPoint slide