Synthesis and pharmacological properties of novel benzamide derivatives acting as ligands to the 5-hydroxytryptamine 4 (5-HT4) receptor

Autor:	Katsuhiko Itoh, Keiichiro Haga, Shuji Sonda, Masatake Fujimura, Takeshi Kawakita, Kiyoshi Asano, Noriko Sato, Hidetoshi Hakira, Hideo Tomozane
Rok vydání:	1999
Předmět:	Pharmacology Agonist Gastric emptying medicine.drug_class Organic Chemistry 5-HT4 receptor Azasetron General Medicine musculoskeletal system Receptor antagonist chemistry.chemical_compound chemistry Drug Discovery medicine Benzamide Receptor 5-HT receptor medicine.drug
Zdroj:	European Journal of Medicinal Chemistry. 34:1101-1108
ISSN:	0223-5234
DOI:	10.1016/s0223-5234(99)00125-7
Popis:	Aseries of 4-amino-5-chloro-2-methoxy-N-(1-substituted piperidin-4-ylmethyl)benzamides was synthesized as novel gastroprokinetic agents. The affinity of these compounds for the 5-hydroxytryptamine 4 (5-HT4) receptor was evaluated. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (3f, Y-34959) showed a higher affinity for the 5-HT4 receptor (Ki = 0.30 nmol/L) than for other receptors, and was confirmed to be a potent 5-HT4 receptor agonist having contractile effects in the isolated guinea-pig ascending colon (EC50 = 1.2 nmol/L). In dogs, compound 3f increased gastroprokinetic motility of both the gastric antrum and the ascending colon. In addition, this effect on the colon was inhibited by azasetron, a selective 5-HT3 receptor antagonist, demonstrating that the effect of gastroprokinetic agents having 5-HT3 receptor antagonism on the colon were reduced compared with that of selective 5-HT4 receptor agonists.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::496fbe0f15967bf09f33c5fbae276ac7 https://doi.org/10.1016/s0223-5234(99)00125-7 Zobrazit plný text záznamu Full Text from ScienceDirect