Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists

Autor:	Takeshi Kawakita, Shuji Sonda, Koji Kanzaki, Keiichiro Haga, Takanobu Kuroita, Katsuhiko Itoh, Noriko Sato, Hideo Tomozane, Tsuguo Ikebe
Rok vydání:	1999
Předmět:	Pharmacology Agonist medicine.drug_class Chemistry Stereochemistry Organic Chemistry 5-HT4 receptor Carboxamide General Medicine Chemical synthesis chemistry.chemical_compound Drug Discovery medicine Structure–activity relationship Receptor Benzamide 5-HT receptor
Zdroj:	European Journal of Medicinal Chemistry. 34:977-989
ISSN:	0223-5234
DOI:	10.1016/s0223-5234(99)00158-0
Popis:	A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT(4) receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT(4) receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT(4) receptors than the other receptors, including, 5-HT(3) and dopamine D(2) receptors. In addition, compound 24 was confirmed to be a potent 5-HT(4) receptor agonist (ED(50) = 7.0 nM). An interaction model between compound 24 and 5-HT(4) receptor was proposed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97d6b155b250cb35ff1c20be761036b3 https://doi.org/10.1016/s0223-5234(99)00158-0 Zobrazit plný text záznamu Full Text from ScienceDirect