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Design, synthesis and biological evaluation of a novel class of potent TGR5 agonists based on a 4-phenyl pyridine scaffold.

Abstract：

:TGR5, a GPCR, is involved in energy and glucose homeostasis, and as such, is a target for the treatment of diabetes, obesity and other metabolic syndromes. A new class of TGR5 agonists based on a 4-phenyl pyridine scaffold was designed, synthesized and evaluated in vitro and in vivo. Extensive structure-activity relationship studies are reported herein. The most potent compounds 15a, 18b and 18c showed comparable activity with the lead compound 2. 15a had the best potency in vitro but displayed an unfavorable pharmacokinetic profile and was found to be ineffective during an oral glucose tolerance test in imprinting control region mice at a dose of 50 mg/kg.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhu J,Ning M,Guo C,Zhang L,Pan G,Leng Y,Shen J

doi

10.1016/j.ejmech.2013.07.050

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

55-68

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00503-5

journal_volume

69

pub_type

杂志文章

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