Bridgehead-methyl analog of SC-53116 as a 5-HT4 agonist

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Bridgehead-methyl analog of SC-53116 as a 5-HT4 agonist.

Pyrrolizidine benzamide (+/-)-2, the bridgehead-methyl analog of SC-53116, was prepared and evaluated for 5-HT(4) agonism activity in the rat tunica muscularis (TMM) mucosae assay. Compound (+/-)-2 has an EC(50) of 449 nM in the TMM assay, as compared to 23 nM for SC-53116, and 66 nM for the racemate of SC-53116.

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Azaadamantanone 1 was converted to a series of aminoazaadamantane benzamides 9a-d, which were profiled for serotonin receptor activity. Aminomethylazaadamantane SC-54750 is a potent 5-HT(4) agonist and 5-HT(3) antagonist with in vivo efficacy in gastroparesis models and also inhibits cisplatin-induced emesis.

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BACKGROUND Serotonin 5-HT4 receptor (5-HT4-R) agonists are potential therapeutic agents for enterokinetic and cognitive disorders and are marketed for treatment of constipation. The aim of this study was to develop an agonist positron emission tomography (PET) ligand in order to label the active G-protein coupled 5-HT4-R in peripheral and central tissues. For this purpose prucalopride, a high-a...

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Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation

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ژورنال

عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters

سال: 2004

ISSN: 0960-894X

DOI: 10.1016/j.bmcl.2004.04.021