[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone
[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone Basic information
- Product Name:
- [4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone
- Synonyms:
-
- [4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone
- HG-10-102-01
- (4-((5-chloro-4- (methylamino)pyrimidin-2-yl)amino)- 3- methoxyphenyl)(morpholino)methano ne
- LRRK2 INHIBITOR 1
- CS-949
- Methanone, [4-[[5-chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinyl-
- Parkinson’s disease,Leucine-rich repeat kinase 2,inhibit,Ser910,BBB,HG 10 102 01,Radiosynthesis,Mouse embryonic fibroblast cells,Mouse Swiss 3T3 cells,MAP kinase interacting kinase,Ser935,MNK,Mitogen activated protein kinase interacting kinase,HG1010201,PET,Inhibitor,MAPK interacting kinase,HEK293 cells,LRRK2,Positron emission tomography
- HG-10-102-01, 10 mM in DMSO
- CAS:
- 1351758-81-0
- MF:
- C17H20ClN5O3
- MW:
- 377.83
- Product Categories:
-
- Amines, Aromatics, Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals
- Amines
- Aromatics
- Heterocycles
- Intermediates & Fine Chemicals
- Pharmaceuticals
- API
- Mol File:
- 1351758-81-0.mol
[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone Chemical Properties
- Boiling point:
- 641.1±65.0 °C(Predicted)
- Density
- 1.381±0.06 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- insoluble in H2O; ≥18.9 mg/mL in DMSO; ≥7.64 mg/mL in EtOH with ultrasonic
- form
- solid
- pka
- 4.60±0.10(Predicted)
- color
- White to off-white
[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone Usage And Synthesis
Description
HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 20.3 nM). It also inhibits the G2019S, A2016T, and [G2019S+A2016T] mutants of LRRK2 (IC50s = 3.2, 153, and 95.9 nM, respectively). HG-10-102-01 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type and G2019S mutant LRRK2 in cells. When given intraperitoneally, HG-10-102-01 penetrates the blood-brain barrier and inhibits phosphorylation of LRRK2 in the brain as well as the kidney and spleen.
Uses
[4-[[5-Chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinylmethanone is an aminopyrimidine derivative as LRRK2 modulators used for the treatment of Parkinson''s disease.
Definition
ChEBI: HG-10-102-01 is a monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 4-{[5-chloro-4-(methylamino)pyrimidin-2-yl]amino}-3-methoxybenzoic acid with the amino group of morpholine. It is an inhibitor of leucine-rich repeat kinase 2 (LRRK2). It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor. It is an aminopyrimidine, a member of morpholines, a monocarboxylic acid amide, an organochlorine compound, a secondary amino compound and an aromatic ether.
in vivo
HG-10-102-01 (0-100 mg/kg, IP, once) shows inhibition of LRRK2 Ser910/Ser935 phosphorylation in kidney, spleen, and brain of mice[1].
HG-10-102-01 (1 mg/kg, IV; 10 mg/kg, PO; once) shows good oral bioavailability (%F = 67), a short half-life of 0.13 h, and low plasma exposure[1].
| Animal Model: | Wild type male C57BL/6 mice[1] |
| Dosage: | 0, 3, 10, 30, 50, and 100 mg/kg |
| Administration: | IP, once |
| Result: | Showed near complete dephosphorylation of Ser910 and Ser935 of LRRK2 in all tissues including brain at 100 mg/kg and 50 mg/kg, but only partial inhibition in brain at the 30 and 10 mg/kg doses. |
| Animal Model: | Wild type male C57BL/6 mice[1] | |||||||||||||||||||||||||||
| Dosage: | 1 mg/kg (IV); 10 mg/kg (PO) | |||||||||||||||||||||||||||
| Administration: | IV, PO; once (Pharmacokinetic Analysis) | |||||||||||||||||||||||||||
| Result: | Pharmacokinetic Parameters of HG-10-102-01 in male C57BL/6 mice[1].
|
References
[1] choi hg1, zhang j, deng x, hatcher jm, patricelli mp, zhao z, alessi dr, gray ns. brain penetrant lrrk2 inhibitor. acs med chem lett. 2012 aug 9;3(8):658-662. epub 2012 jun 18.
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