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Updated: May 24, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Novel 3,6,7-substituted pyrazolopyrimidines as positive allosteric modulators for the hydroxycarboxylic acid receptor
Clara C Blad1, Jacobus P D van Veldhoven, Corné Klopman
1Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Abstract:
A number of pyrazolopyrimidines were synthesized and tested for their positive allosteric modulation of the HCA(2) receptor (GPR109A). Compound 24, an efficacious and potent agonist and allosteric enhancer of nicotinic acid's action, was the basis for most other compounds. Interestingly, some of the compounds were found to increase the efficacy of the endogenous ligand 3-hydroxybutyrate and enhance its potency almost 10-fold. This suggests that the pyrazolopyrimidines may have therapeutic value when given alone.
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