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2-Aminoalkyl nicotinamide derivatives as pure inverse agonists of the ghrelin receptor.

Abstract：

:New inverse agonists of the ghrelin receptor (ghrelinR) were obtained through high-throughput screening and subsequent structural modification of 2-aminoalkyl nicotinamide derivatives. The key structural feature to improve in vitro activity was the introduction of a diazabicyclo ring at the 5-position of the pyridine ring. The final product showed potent inverse agonist activity and, despite its low brain permeability, reduced food intake in both normal and obese mice. These results implied that peripheral ghrelinR activity is important for appetite control and that a peripheral ghrelinR inverse agonist could be an anti-obesity drug with reduced risk of central nervous system (CNS)-related side effects.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Takahashi B,Funami H,Iwaki T,Maruoka H,Nagahira A,Koyama M,Kamiide Y,Matsuo T,Muto T,Annoura H

doi

10.1016/j.bmcl.2015.04.040

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

2707-12

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00360-1

journal_volume

25

pub_type

杂志文章

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