5-HT2B and 5-HT7 receptors exist in smooth muscle and neurons in gastrointestinal tract, and are involved in abnormal bowel movement and abdominal pain of IBS (irritable bowel syndrome). Therefore, dual antagonists of 5-HT2B/7 receptors are expected to improve of the symptoms of IBS. In an effort to develop 5-HT2B/7 receptors antagonists, we have synthesized a series of novel indole derivatives. Among these compounds, 3-ethyl-1-[(4-fluorophenyl)methyl]-2-methyl-N-[(3S)-1-methylpyrrolidin-3-yl]-1H-indole-5-carboxamide (ASP1017) showed potent antagonistic activity to 5-HT2B/7 receptors and high selectivity. And also, ASP1017  inhibited stress-induced defecation and abdominal pain in rats. Synthesis and structure-activity relationships of a novel series of indole derivatives, including in vivo evaluation of ASP1017 will be presented.

Novel and potent 5-HT<sub>2B/7 </sub>receptors antagonists for the treatment of IBS

246th National Meeting (2013)

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Novel and potent 5-HT2B/7 receptors antagonists for the treatment of IBS

Novel and potent 5-HT_2B/7receptors antagonists for the treatment of IBS