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

Clara C. Blad, Jacobus P D Van Veldhoven, Corné Klopman, Dieter R. Wolfram, Johannes Brussee, J. Robert Lane, Adriaan P IJzerman

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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.

Original languageEnglish
Pages (from-to)3563-3567
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number7
Publication statusPublished - 12 Apr 2012
Externally publishedYes

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