| Identification | Back Directory | [Name]
[4,4'-Bipyrimidin]-6(1H)-one, 2-[(2S)-2-(4-fluorophenyl)-4-morpholinyl]-1-methyl- | [CAS]
503860-57-9 | [Synonyms]
SAR502250
SAR-502250,SAR502250
(S)-2-(2-(4-fluorophenyl)morpholino)-1-methyl-[4,4'-bipyrimidin]-6(1H)-one
[4,4'-Bipyrimidin]-6(1H)-one, 2-[(2S)-2-(4-fluorophenyl)-4-morpholinyl]-1-methyl- | [Molecular Formula]
C19 H18 F N5 O2 | [MDL Number]
MFCD33023233 | [MOL File]
503860-57-9.mol | [Molecular Weight]
367.38 |
| Chemical Properties | Back Directory | [Boiling point ]
547.2±60.0 °C(Predicted) | [density ]
1.38±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (272.20 mM; Need ultrasonic) | [form ]
Solid | [pka]
2.90±0.19(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD)[1][2]. | [in vivo]
SAR502250 (1-100 mg/kg; a single p.o,) attenuates tau hyperphosphorylation in the cortex and spinal cord of transgenic mice expressing P301L tau[2].
SAR502250 (10-30 mg/kg; p.o. once daily for 7 weeks) improves the cognitive deficit in transgenic APP(SW)/Tau(VLW) mice after infusion of Aβ25-35[2].
SAR502250 (10-30?mg/kg; a single p.o.) significantly increases the percentage of lever-presses in the inter-response time (IRT) bin (49-96?s), with a significant augmentation of the percentage of reinforced responses[2].
SAR502250 (30?mg/kg; i.p. once daily for 28 d) ameliorates chronic stress-induced degradation of the physical state of the mice coat[2].
SAR502250 (10-60 mg/kg; a single p.o.) decreases hyperactivity produced by psychostimulantsin mice[2]. | Animal Model: | Female P301L human tau transgenic mice (three-month-old; 32 g)[2] | | Dosage: | 1, 3, 10, 30, 100 mg/kg | | Administration: | A single p.o. | | Result: | Attenuated dose-dependently tau phosphorylation in the cortex and spinal cord, with ED50s of 12.5 and 11.5?mg/kg, respectively. |
| [IC 50]
hGSK-3β: 12 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Fukunaga K, et, al. 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7. DOI:10.1016/j.bmcl.2013.09.020
[2] Griebel G, et, al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer's disease in rodents. Sci Rep. 2019 Dec 2;9(1):18045. DOI:10.1038/s41598-019-54557-5 |
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