The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties

Jason E Imbriglio; Daniel DiRocco; Rena Bodner; Subharekha Raghavan; Weichun Chen; Daria Marley; Craig Esser; Tom G Holt; Michael S Wolff; Andrew K P Taggart; M Gerard Waters; James R Tata; Steven L Colletti

doi:10.1016/j.bmcl.2010.11.116

The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties

Bioorg Med Chem Lett. 2011 May 1;21(9):2721-4. doi: 10.1016/j.bmcl.2010.11.116. Epub 2010 Dec 4.

Authors

Jason E Imbriglio¹, Daniel DiRocco, Rena Bodner, Subharekha Raghavan, Weichun Chen, Daria Marley, Craig Esser, Tom G Holt, Michael S Wolff, Andrew K P Taggart, M Gerard Waters, James R Tata, Steven L Colletti

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065-0900, USA. jason_imbriglio@merck.com

PMID: 21185185
DOI: 10.1016/j.bmcl.2010.11.116

Abstract

Amino-anthranilic acid derivatives have been identified as a new class of low serum shifted, high affinity full agonists of the human orphan G-protein-coupled receptor GPR109a with improved ADME properties.

MeSH terms

Animals
Drug Discovery*
Fluorine / chemistry
Humans
Inhibitory Concentration 50
Mice
Molecular Structure
Niacin / chemical synthesis
Niacin / chemistry
Niacin / pharmacology
Pyridines / chemical synthesis
Pyridines / chemistry
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled / agonists*
Receptors, Nicotinic

Substances

HCAR2 protein, human
Pyridines
Receptors, G-Protein-Coupled
Receptors, Nicotinic
Niacin
Fluorine