title: Synthesis and pharmacological properties of benzamide derivatives as selective serotonin 4 receptor agonists.
abstract: A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2-methoxybenzamide (13a, Y-36912), was a selective 5-HT4 receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.
authors.affiliation: Pharmaceutical Development Laboratories, Technology and Production Division, Mitsubishi Pharma Corporation, 14, Sunayama, Hasaki-machi, Kashima, Ibaraki 314-0255, Japan. sonda.shuuji@ma.m-pharma.co.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Sonda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Katayama
authors.forename: Toshio
authors.initials: T
authors.lastname: Kawahara
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asano
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D015394:Molecular Structure; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists