Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5

Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes. Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes.

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 20; no. 19; pp. 5718 - 5721
Main Authors:	Herbert, Mark R., Siegel, Dana L., Staszewski, Lena, Cayanan, Charmagne, Banerjee, Urmi, Dhamija, Sangeeta, Anderson, Jennifer, Fan, Amy, Wang, Li, Rix, Peter, Shiau, Andrew K., Rao, Tadimeti S., Noble, Stewart A., Heyman, Richard A., Bischoff, Eric, Guha, Mausumee, Kabakibi, Ayman, Pinkerton, Anthony B.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 01-10-2010 Elsevier
Subjects:	Animals Bile acids Biological and medical sciences Diabetes Diabetes Mellitus, Type 2 - drug therapy General and cellular metabolism. Vitamins Glucagon-Like Peptide 1 - metabolism GPCRs Hydroxyquinolines - chemical synthesis Hydroxyquinolines - chemistry Hydroxyquinolines - therapeutic use Medical sciences Mice Pharmacology. Drug treatments Quinolines - chemical synthesis Quinolines - chemistry Quinolines - therapeutic use Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - metabolism Structure-Activity Relationship TGR5 Thiophenes - chemical synthesis Thiophenes - chemistry Thiophenes - therapeutic use TGR5 Bile acids Diabetes GPCRs Endocrinopathy Steroid Agonist Diabetes mellitus Rodentia Quinoline derivatives Glucose tolerance test Thiophene derivatives Vertebrata Hypoglycemic agent Mammalia TGR5 receptor Structure activity relation G protein coupled receptor Bile acid Bromine Organic compounds Chemical synthesis
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Summary:	Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes. Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.08.014