For research purposes only

Cat. No BA94673139

Availability - up to 10 mg in stock
- larger amount can be synthesized in 8 weeks

Description of biological activity

Positive allosteric modulator (PAM), selective for the metabotropic glutamate receptor subtype mGluR5, showed nootropic and antipsychotic effects in animal studies.The compound is a potent and selective mGluR5 PAM, increased (9-fold) the response to threshold concentration of glutamate (50 nM) in fluorometric Ca2+ assays (EC50 =170 nM) in human embryonic kidney 293 cells expressing rat mGluR5. In the same system, ADX-47273 dose-dependently shifted mGluR5 receptor glutamate response curve to the left (9-fold at 1 μM) and competed for binding of [[3H]]2-methyl-6-(phenylethynyl)pyridine (Ki = 4.3 μM), but not [[3H]]quisqualate. In vivo, ADX-47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. In models sensitive to antipsychotic drug treatment, ADX-47273 reduced rat-conditioned avoidance responding [minimal effective dose (MED) = 30 mg/kg i.p.] and decreased mouse apomorphine-induced climbing (MED = 100 mg/kg i.p.), with little effect on stereotypy or catalepsy. Furthermore, ADX47273 blocked phencyclidine, apomorphine, and amphetamine-induced locomotor activities (MED = 100 mg/kg i.p.) in mice and decreased extracellular levels of dopamine in the nucleus accumbens, but not in the striatum, in rats. In cognition models, ADX-47273 increased novel object recognition (MED = 1 mg/kg i.p.) and reduced impulsivity in the five choice seria

Keywords: CNS disorders

TECHNICAL INFORMATION

(S)-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone positive allosteric modulator (PAM)

IUPAC Name: (S)-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone

CAS Number: 851881-60-2

Purity: > 96% chemical purity (LCMS)

1H-NMR spectrum (click to enlarge)

REFERENCES

1. J. Med. Chem. 49 (11): 3332-44
2. Journal of Pharmacology and Experimental Therapeutics 327 (3): 827-39

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