2. Academic Validation
  3. Discovery and pharmacological profile of new 1H-indazole-3-carboxamide and 2H-pyrrolo[3,4-c]quinoline derivatives as selective serotonin 4 receptor ligands

Discovery and pharmacological profile of new 1H-indazole-3-carboxamide and 2H-pyrrolo[3,4-c]quinoline derivatives as selective serotonin 4 receptor ligands

  • J Med Chem. 2012 Nov 26;55(22):9446-66. doi: 10.1021/jm300573d.
Guido Furlotti 1,  Maria Alessandra Alisi,  Claudia Apicella,  Alessandra Capezzone de Joannon,  Nicola Cazzolla,  Roberta Costi,  Giuliana Cuzzucoli Crucitti,  Beatrice Garrone,  Alberto Iacovo,  Gabriele Magarò,  Giorgina Mangano,  Gaetano Miele,  Rosella Ombrato,  Luca Pescatori,  Lorenzo Polenzani,  Federica Rosi,  Marco Vitiello,  Roberto Di Santo
Affiliations

Affiliation

  • 1 Department of Chemistry, Angelini Santa Palomba Research Center, Piazzale della Stazione snc, 00040 Pomezia, Italy. g.furlotti@angelini.it
PMID: 23043420 DOI: 10.1021/jm300573d
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.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z