Novel 3,6,7-Substituted Pyrazolopyrimidines as Positive Allosteric Modulators for the Hydroxycarboxylic Acid Receptor 2 (GPR109A)
A number of pyrazolopyrimidines were synthesized and tested for their positive allosteric modulation of the HCA2 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 c...
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| Veröffentlicht in: | Journal of medicinal chemistry 2012-04, Vol.55 (7), p.3563-3567 |
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| container_end_page | 3567 |
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| container_issue | 7 |
| container_start_page | 3563 |
| container_title | Journal of medicinal chemistry |
| container_volume | 55 |
| creator | Blad, Clara C van Veldhoven, Jacobus P. D Klopman, Corné Wolfram, Dieter R Brussee, Johannes Lane, J. Robert IJzerman, Adriaan P |
| description | A number of pyrazolopyrimidines were synthesized and tested for their positive allosteric modulation of the HCA2 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. |
| doi_str_mv | 10.1021/jm300164q |
| format | Article |
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Robert</au><au>IJzerman, Adriaan P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel 3,6,7-Substituted Pyrazolopyrimidines as Positive Allosteric Modulators for the Hydroxycarboxylic Acid Receptor 2 (GPR109A)</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2012-04-12</date><risdate>2012</risdate><volume>55</volume><issue>7</issue><spage>3563</spage><epage>3567</epage><pages>3563-3567</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>A number of pyrazolopyrimidines were synthesized and tested for their positive allosteric modulation of the HCA2 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. 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| ispartof | Journal of medicinal chemistry, 2012-04, Vol.55 (7), p.3563-3567 |
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| source | MEDLINE; ACS Publications |
| subjects | 3-Hydroxybutyric Acid - metabolism Allosteric Regulation Drug Synergism Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology HEK293 Cells Humans Niacin - pharmacology Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacology Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Radioligand Assay Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - metabolism Receptors, Nicotinic - metabolism Structure-Activity Relationship |
| title | Novel 3,6,7-Substituted Pyrazolopyrimidines as Positive Allosteric Modulators for the Hydroxycarboxylic Acid Receptor 2 (GPR109A) |
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