Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A

Hong C Shen; Andrew K P Taggart; Larissa C Wilsie; M Gerard Waters; Milton L Hammond; James R Tata; Steven L Colletti

doi:10.1016/j.bmcl.2008.08.039

Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A

Bioorg Med Chem Lett. 2008 Sep 15;18(18):4948-51. doi: 10.1016/j.bmcl.2008.08.039. Epub 2008 Aug 14.

Authors

Hong C Shen¹, Andrew K P Taggart, Larissa C Wilsie, M Gerard Waters, Milton L Hammond, 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. hong_shen@merck.com

PMID: 18752940
DOI: 10.1016/j.bmcl.2008.08.039

Abstract

Pyrazolopyrimidines were discovered as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. In addition to its intrinsic activity, compound 9n significantly enhances nicotinic acid binding to the receptor, thereby potentiating the functional efficacy of nicotinic acid.

MeSH terms

Binding Sites
Combinatorial Chemistry Techniques
Humans
Molecular Structure
Niacin / metabolism
Nicotinic Agonists / chemical synthesis*
Nicotinic Agonists / chemistry
Nicotinic Agonists / pharmacology*
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Receptors, G-Protein-Coupled / agonists*
Receptors, Nicotinic
Structure-Activity Relationship

Substances

HCAR2 protein, human
HCAR3 protein, human
Nicotinic Agonists
Pyrazoles
Pyrimidines
Receptors, G-Protein-Coupled
Receptors, Nicotinic
Niacin