Novel 3,6,7-Substituted Pyrazolopyrimidines as Positive Allosteric Modulators for the Hydroxycarboxylic Acid Receptor 2 (GPR109A)

作者：Blad Clara C; van Veldhoven Jacobus P D; Klopman Corne; Wolfram Dieter R; Brussee Johannes; Lane J Robert; IJzerman Adriaan P^*

来源：Journal of Medicinal Chemistry, 2012, 55(7): 3563-3567.

DOI：10.1021/jm300164q

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%26apos;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.

• 出版日期2012-4-12