| Identification | Back Directory | [Name]
JNJ-42226314 | [CAS]
1252765-13-1 | [Synonyms]
JNJ-42226314
JNJ42226314,JNJ 42226314
1-(4-Fluorophenyl)-5-indolyl][3-[4-(thiazole-2-carbonyl)-1-piperazinyl]-1-azetidinyl]methanone
Methanone, [4-[1-[[1-(4-fluorophenyl)-1H-indol-5-yl]carbonyl]-3-azetidinyl]-1-piperazinyl]-2-thiazolyl- | [Molecular Formula]
C26H24FN5O2S | [MDL Number]
MFCD32671350 | [MOL File]
1252765-13-1.mol | [Molecular Weight]
489.56 |
| Chemical Properties | Back Directory | [Boiling point ]
624.9±65.0 °C(Predicted) | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [pka]
5.68±0.70(Predicted) | [color ]
White to off-white | [InChIKey]
IVOACCSOISMVBL-UHFFFAOYSA-N | [SMILES]
C(N1CCN(C2CN(C(C3C=CC4=C(C=3)C=CN4C3=CC=C(F)C=C3)=O)C2)CC1)(C1=NC=CS1)=O |
| Hazard Information | Back Directory | [Uses]
JNJ-42226314 is a competitive, highly selective and reversible non-covalent monoacylglycerol lipase (MAGL) inhibitor. JNJ-42226314 demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol (2-AG) as well as efficacy in models of neuropathic and inflammatory pain[1]. | [Biological Activity]
Brain penetranthighly selective and potent reversible inhibitor of monoacylglycerol lipase (MAGL).
JNJ-42226314 is a brain penetranthighly selective and potent reversible inhibitor of monoacylglycerol lipase (MAGL)(IC50 = 1.1) th at exhibits antinociceptive efficacy in the r at models neuropathic and inflammatory pain. JNJ-42226314 elevates hippocampal 2-arachidonoylglycerol (2-AG) levels and prolongs wakefulness in rats. | [in vivo]
JNJ-42226314 (i.p.; 3 mg/kg and 30 mg/kg; 120 min) dose-dependently elevates hippocampal 2-AG in vivo[1].
JNJ-42226314 (i.p.; 30 mg/kg)significantly increases total wake time for up to 8 hours afterward, whereas total wake time was only elevated for 2 hr following a 3 mg/kg dose[1].
JNJ-42226314 (i.p.; 30 mg/kg) is antinociceptive in the rat complete Freund’s adjuvant (CFA) model of inflammatory pain[1].
JNJ-42226314 has t1/2 values of 11.4, 27.6, 27.2 min for MAGL in human, mouse and rat, respectively[1].
| Animal Model: | Male C57Bl/6 mice weighing 20-30g and male Sprague-Dawley rats weighing 300-400 g[1] | | Dosage: | 3 mg/kg and 30 mg/kg | | Administration: | i.p.; 120 min | | Result: | Dose-dependently elevated hippocampal 2-AG in vivo.
|
| [References]
[1] Wyatt RM, et al.Pharmacologic characterization of JNJ-42226314, [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a reversible, selective and potent monoacylglycerol lipase inhibitor.J Pharmacol Exp Ther. 2019 Dec 9. DOI:10.1124/jpet.119.262139 |
|
|