| Identification | Back Directory | [Name]
1H-Imidazole-5-acetonitrile, 1-[2-[[(3S)-1-(cyclopropylcarbonyl)-3-piperidinyl]amino]-4-pyrimidinyl]-2-(2-naphthalenyl)- | [CAS]
2409109-65-3 | [Synonyms]
JNK3 inhibitor-4
1H-Imidazole-5-acetonitrile, 1-[2-[[(3S)-1-(cyclopropylcarbonyl)-3-piperidinyl]amino]-4-pyrimidinyl]-2-(2-naphthalenyl)- | [Molecular Formula]
C28H27N7O | [MOL File]
2409109-65-3.mol | [Molecular Weight]
477.56 |
| Chemical Properties | Back Directory | [Boiling point ]
814.7±75.0 °C(Predicted) | [density ]
1.37±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
2.31±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
JNK3 inhibitor-4 is a potent inhibitor of JNK3 (IC50=1.0 nM) based on 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile. JNK3 inhibitor-4 shows excellent selectivity over other protein kinases including isoforms JNK1 (IC50=143.9 nM) and JNK2 (IC50=298.2 nM)[1]. JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability[1]. | [in vivo]
JNK3 inhibitor-4 improves memory for the Alzheimer’s disease mouse model. JNK3 inhibitor-4 (compound 15d) (10 or 30 mg/kg; i.v.; 3 times/week for 1 month in 9-month-old APP/PS1 3Tx3Tg mice) results significantly higher spontaneous alteration and response latency of mouse (at 27th or 30th days) compared to the APP/PS1vehicle groups in Y-maze test and passive avoidance test, with a dose correlation[1].
JNK3 inhibitor-4 (30 mg/kg; p.o.; single dose) shows blood-brain barrier permeability with brain to plasma ratio of 0.02 in SD rats[1].
Pharmacokinetics in rats[1]
| Route | Dose (mg/kg) | AUC0-t (ng·h/mL) | Cmax (ng/mL) | Tmax (h) | T1/2 (h) | BA (%) | | IV | 1 | 718.0 | | | 0.22 | | | PO | 3 | 337.5 | 377.82 | 0.63 | 0.34 | 15.67 |
| [IC 50]
JNK3: 1.0 nM (IC50); JNK1: 143.9 nM (IC50); JNK2: 298.2 nM (IC50) | [References]
[1] Jun J, et al. Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114894. DOI:10.1016/j.ejmech.2022.114894 |
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