Add time:08/09/2019         Source:sciencedirect.com

It is thought that selective 5-HT4 receptor agonists—such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4-ylmethyl]benzamide (2)—have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects.Modification of 2 was performed. Variation of the piperidin-4-ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT4 receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT4 receptor.Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT4 receptor agonists, and had a similar effect on defecation to compound 2.

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