Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT(4) receptor agonists
| Autor: | Ken-ichi Katayama, Noriko Sato, Toshio Kawahara, Shuji Sonda, Kiyoshi Asano |
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| Rok vydání: | 2004 |
| Předmět: |
Agonist
Male medicine.drug_class Stereochemistry Clinical Biochemistry Guinea Pigs Drug Evaluation Preclinical Pharmaceutical Science 5-HT4 receptor Biochemistry Chemical synthesis chemistry.chemical_compound Mice Serotonin 5-HT4 Receptor Agonists Drug Discovery medicine Moiety Animals Rats Wistar Benzamide Receptor Molecular Biology Mice Inbred ICR Molecular Structure Receptors Dopamine D2 Organic Chemistry Sulfoxide Biological activity Rats chemistry Benzamides Molecular Medicine Gastrointestinal Motility |
| Zdroj: | Bioorganicmedicinal chemistry. 13(9) |
| ISSN: | 0968-0896 |
| Popis: | It is thought that selective 5-HT 4 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-HT 4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT 4 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-HT 4 receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT 4 receptor agonists, and had a similar effect on defecation to compound 2 . |
| Databáze: | OpenAIRE |
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