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3-(cyclopropylMethyl)-7-(4-phenylpiperidin-1-yl)-8-(trifluoroMethyl)-[1,2,4]triazolo[4,3-a]pyridine
For research use only. Not for therapeutic Use.
JNJ-42153605 is a potent and selective mGlu2 receptor PAM with an acceptable pharmacokinetic profile in rodent and nonrodent species. JNJ-42153605 showed centrally mediated in vivo effectivity in models sensitive to mGlu2 receptor modulation such as sleep−wake electroencephalogram (sw-EEG) in rats,34 showing suppressed REM sleep during the first 4 h after oral administration of a 3 mg/kg dose.
Catalog Number | M015474 |
CAS Number | 1254977-87-1 |
Synonyms | 3-(cyclopropylMethyl)-7-(4-phenylpiperidin-1-yl)-8-(trifluoroMethyl)-[1,2,4]triazolo[4,3-a]pyridine |
Molecular Formula | C22H23F3N4 |
Purity | ≥95% |
Target | Neuronal Signaling |
Storage | -20°C |
IUPAC Name | 3-(cyclopropylmethyl)-7-(4-phenylpiperidin-1-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine |
InChI | InChI=1S/C22H23F3N4/c23-22(24,25)20-18(10-13-29-19(14-15-6-7-15)26-27-21(20)29)28-11-8-17(9-12-28)16-4-2-1-3-5-16/h1-5,10,13,15,17H,6-9,11-12,14H2 |
InChIKey | BQAVZGJJQFJSMW-UHFFFAOYSA-N |
SMILES | C1CC1CC2=NN=C3N2C=CC(=C3C(F)(F)F)N4CCC(CC4)C5=CC=CC=C5 |
Reference | 1:J Med Chem. 2012 Oct 25;55(20):8770-89. doi: 10.1021/jm3010724. Epub 2012 Oct 16. Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor.Cid JM,Tresadern G,Vega JA,de Lucas AI,Matesanz E,Iturrino L,Linares ML,Garcia A,Andrés JI,Macdonald GJ,Oehlrich D,Lavreysen H,Megens A,Ahnaou A,Drinkenburg W,Mackie C,Pype S,Gallacher D,Trabanco AA, PMID: 23072213 DOI: 10.1021/jm3010724 </br><span>Abstract:</span> Advanced leads from a series of 1,2,4-triazolo[4,3-a]pyridines with mGlu2 receptor PAM activity are reported. By modification of the analogous imidazo[1,2-a]pyridine series, the newly reported leads have improved potency, in vitro ADMET, and hERG as well as good in vivo PK profile. The optimization of the series focused on improving metabolic stability while controlling lipophilicity by introducing small modifications to the scaffold substituents. Analysis of this series combined with our previously reported mGlu2 receptor PAMs showed how lipophilic ligand efficiency was improved during the course of the program. Among the best compounds, example 20 (JNJ-42153605) showed a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown earlier to be mGlu2 mediated. In mice, compound 20 reversed PCP-induced hyperlocomotion with an ED₅₀ of 5.4 mg/kg sc, indicative of antipsychotic activity. |