Abstract:
:Since the discovery of the serotonin 4 receptor (5-HT(4)R), 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-HT(4)R 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 (11 ab and 12 g) were identified as potent and selective 5-HT(4)R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12 g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT(4)R antagonist with analgesic action.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo Rdoi
10.1021/jm300573dsubject
Has Abstractpub_date
2012-11-26 00:00:00pages
9446-66issue
22eissn
0022-2623issn
1520-4804journal_volume
55pub_type
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