Twenty-three indole-3-methanamines were designed, synthesized and evaluated as ligands for the 5-HT4 receptor. Compounds I-d, I-J, I-o, I-q and I-u showed good affinity at 100 mu M and I-o was found to be only 5-fold less potent than the agonists serotonin (1) and 5-methoxytryptamine (2). Substitution on the 3-methanamine nitrogen clearly influenced activity with docking experiments into a homology model of the 5-HT4 receptor showing a range of interactions with these side chain substituents. This modelling work together with the SAR determined in this study has provided promising ideas for future synthetic work. (C) 2009 Elsevier Masson SAS. All rights reserved.
|Pages (from-to)||2952 - 2959|
|Number of pages||8|
|Journal||European Journal of Medicinal Chemistry|
|Publication status||Published - 2009|