Novel 3, 6, 7-substituted pyrazolopyrimidines as positive allosteric modulators for the hydroxycarboxylic acid receptor 2 (GPR109A)

Blad, Clara C; van Veldhoven, Jacobus P D; Klopman, Corn�; Wolfram, Dieter R; Brussee, Johannes; Lane, J Robert; Ijzerman, Adriaan P

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.

Citation

Blad, C. C., van Veldhoven, J. P. D., Klopman, C., Wolfram, D. R., Brussee, J., Lane, J. R., & Ijzerman, A. P. (2012). Novel 3, 6, 7-substituted pyrazolopyrimidines as positive allosteric modulators for the hydroxycarboxylic acid receptor 2 (GPR109A). Journal of Medicinal Chemistry, 55(7), 3563-3567. https://doi.org/10.1021/jm300164q

• Journal Article Type: Article
• Acceptance Date: Oct 24, 2011
• Online Publication Date: Mar 27, 2012
• Publication Date: Mar 15, 2012
• Deposit Date: Apr 22, 2020
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 55
• Issue: 7
• Pages: 3563-3567
• DOI: https://doi.org/10.1021/jm300164q
• Public URL: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22420767&retmode=ref&cmd=prlinks
• Publisher URL: https://pubs.acs.org/doi/full/10.1021/jm300164q