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

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

  • Eur J Med Chem. 2013 Nov:69:55-68. doi: 10.1016/j.ejmech.2013.07.050.
Junjie Zhu 1,  Mengmeng Ning,  Cen Guo,  Lina Zhang,  Guoyu Pan,  Ying Leng,  Jianhua Shen
Affiliations

Affiliation

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
PMID: 24007860 DOI: 10.1016/j.ejmech.2013.07.050
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.

Keywords

4-Phenyl pyridine; Diabetes; GPCR; TGR5.

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