Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists

Xuqing Zhang; Zhihua Sui; Jack Kauffman; Cuifen Hou; Cailin Chen; Fuyong Du; Thomas Kirchner; Yin Liang; Dana Johnson; William V Murray; Keith Demarest

doi:10.1016/j.bmcl.2017.02.069

Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists

Bioorg Med Chem Lett. 2017 Apr 15;27(8):1760-1764. doi: 10.1016/j.bmcl.2017.02.069. Epub 2017 Feb 28.

Authors

Affiliations

¹ Cardiovascular and Metabolic Research, Janssen Research & Development, LLC, Welsh & McKean Roads, Box 776, Spring House, PA 19477, United States. Electronic address: [email protected].
² Cardiovascular and Metabolic Research, Janssen Research & Development, LLC, Welsh & McKean Roads, Box 776, Spring House, PA 19477, United States.

PMID: 28285911
DOI: 10.1016/j.bmcl.2017.02.069

Abstract

A novel series of 2-thio-5-thiomethyl substituted imidazoles was discovered to be potent TGR5 agonists that possessed glucose-lowering effects while inhibiting gall bladder emptying in mice.

Keywords: Gall bladder; Imidazole; OGTT; TGR5.

MeSH terms

Animals
Blood Glucose / analysis
Blood Glucose / metabolism
Cell Line
Diabetes Mellitus / blood
Diabetes Mellitus / drug therapy*
Diabetes Mellitus / metabolism
Diabetes Mellitus / physiopathology
Gallbladder Emptying / drug effects*
Humans
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use*
Imidazoles / chemistry*
Imidazoles / pharmacology
Imidazoles / therapeutic use*
Methylation
Mice
Mice, Inbred C57BL
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / metabolism

Substances

Blood Glucose
GPBAR1 protein, human
Hypoglycemic Agents
Imidazoles
Receptors, G-Protein-Coupled