Synthesis and Evaluation of Novel 2-Oxo-1,2-dihydro-3-quinolinecar- boxamide Derivatives as Potent and Selective Serotonin 5-HT 4 Receptor Agonists

its existence in the gut was later proved. 5-HT 4 receptors in the gut are suggested to participate in the induction and maintenance of gastrointestinal motility. It has been reported that 5-HT4 receptor agonists, cisapride 4) and renzapride, 5,6) are reported to increase gastrointestinal motility and improve gastrointestinal condition. We recently reported N-(endo-8methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2dihydro-3-quinolinecarboxamide (10a) as a potent 5-HT4 receptor agonist. 7) In the course of study, 1-alkyl substituents had a great influence upon 5-HT4 receptor agonistic activity. Next, we took note of an influence of 89-alkyl substituents upon 5-HT4 receptor agonistic activity. In the present study, we synthesized and evaluated 89-position substituted N(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives with the aim of finding more potent and selective 5-HT4 receptor agonists. Chemistry