N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide
N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide Basic information
- Product Name:
- N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide
- Synonyms:
-
- CZC-25146
- N-[2-[[5-Fluoro-2-[[2-methoxy-4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]amino]phenyl]methanesulfonamide
- N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide
- N-(2-((5-fluoro-2-((2-methoxy-4- morpholinophenyl)amino)pyrimidin- 4- yl)amino)phenyl)methanesulfonamide
- LRRK2 Inhibitor II
- LRRK2 INHIBITOR II;CZC25146;CZC 25146
- CHEMBL2397014
- Methanesulfonamide, N-[2-[[5-fluoro-2-[[2-methoxy-4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]amino]phenyl]-
- CAS:
- 1191911-26-8
- MF:
- C22H25FN6O4S
- MW:
- 488.54
- Product Categories:
-
- Amines, Aromatics, Heterocycles, Inhibitors, Pharmaceuticals, Intermediates & Fine Chemicals
- API
- Mol File:
- 1191911-26-8.mol
N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide Chemical Properties
- Boiling point:
- 697.4±65.0 °C(Predicted)
- Density
- 1.436±0.06 g/cm3(Predicted)
- storage temp.
- under inert gas (nitrogen or Argon) at 2-8°C
- solubility
- ≥24.45 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
- form
- solid
- pka
- 8.48±0.10(Predicted)
- color
- Pale purple to purple
N-(2-(2-(2-Methoxy-4-MorpholinophenylaMino)-5-fluoropyriMidin-4-ylaMino)phenyl)MethanesulfonaMide Usage And Synthesis
Description
CZC-25146 is a potent inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 4.76 nM for the human recombinant kinase). It also inhibits LRRK2G2019S, a mutant linked to neurotoxicity and Parkinson’s disease, with an IC50 value of 6.87 nM. CZC-25146 is selective for LRRK2 over a panel of kinases in HeLa cell lysates, Jurkat/Ramos mixed cell lysates, as well as whole mouse brain extracts (IC50s = >2 μM). It reduces LRRK2G2019S-induced cell injury in rat primary cortical neurons.
Uses
CZC-25146 is a compound that acts as an inhibitor of LRRK2, a factor in the expression of Parkinsons’s disease, and is ATP-competitive.
in vivo
CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice[3].
CZC-25146 (1 mg/kg for i.v.; 5 mg/kg for p.o.; single dosage) exhibits relatively good pharmacokinetic properties and an extensive distribution throughout animal body following intravenous injection into mice[1].
| Animal Model: | Genetically modified male mice (6 weeks; over expressing human polymeric ATZ)[3] |
| Dosage: | 250 mg/kg |
| Administration: | p.o.; 14 days |
| Result: | Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%. |
| Animal Model: | Male CD-1 mice[1] | |||||||||||||||||||||||||||
| Dosage: | 1 mg/kg for i.v.; 5 mg/kg for p.o. | |||||||||||||||||||||||||||
| Administration: | i.v. and p.o.; single dosage | |||||||||||||||||||||||||||
| Result: | Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice[1].
|
storage
Store at -20°C
References
[1] ramsden n, perrin j, ren z, et al. chemoproteomics-based design of potent lrrk2-selective lead compounds that attenuate parkinson’s disease-related toxicity in human neurons. acs chemical biology, 2011, 6(10): 1021-1028.
[2] troxler t, greenidge p, zimmermann k, et al. discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of lrrk2. bioorganic & medicinal chemistry letters, 2013, 23(14): 4085-4090.
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