NOVEL 5-HYDROXYTRYPTAMINE-4 (5-HT4) RECEPTOR AGONISTS - SYNTHESIS ANDGASTROPROKINETIC ACTIVITY OF YCLOALKAN-1-YL)ETHYL]-5-CHLORO-2-METHOXYBENZAMIDES

A novel series of cycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamide d erivatives (1), which had amines conformationally restricted due to th e effect of repulsion by neighboring substituents, were prepared and e valuated for 5-hydroxytryptamine 4 (5-HT4) agonistic activities by usi ng the contraction of longitudinal muscle myenteric plexus (LMMP) of g uinea pig ileum. One of the most potent compounds in this series was m ethylamino-1-cyclohexyl)ethyl]-2-methoxybenzamide (1c, YM-47813) with an EC,, value of 1.0 mu M on LMMP. This compound effectively enhanced gastric motility and gastric emptying in conscious dogs by oral admini stration (1-3 mg/kg).