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Furlotti G.,Angelini Santa Palomba Research Center | Alisi M.A.,Angelini Santa Palomba Research Center | Apicella C.,Angelini Santa Palomba Research Center | Capezzone De Joannon A.,Angelini Santa Palomba Research Center | And 14 more authors.
Journal of Medicinal Chemistry | Year: 2012

Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl) methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT 4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action. © 2012 American Chemical Society.

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