5-HT3 receptor antagonists. 3. Quinoline derivatives which may be effective in the therapy of irritable bowel syndrome.

A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT 3 receptor antagonists due to deviation of a carbonyl moiety from the plane of an aromatic ring in their minimum-energy conformations. These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats. Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID 50 =0.27, 0.12, and 0.0052 mg/kg, po, respectively). However, quinoline derivatives exhibited different activities depending on structural class