| Identification | Back Directory | [Name]
[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone | [CAS]
1351758-81-0 | [Synonyms]
CS-949
HG-10-102-01
LRRK2 INHIBITOR 1
[4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone
(4-((5-chloro-4-
(methylamino)pyrimidin-2-yl)amino)-
3-
methoxyphenyl)(morpholino)methano
ne
Methanone, [4-[[5-chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinyl- | [Molecular Formula]
C17H20ClN5O3 | [MDL Number]
MFCD28160565 | [MOL File]
1351758-81-0.mol | [Molecular Weight]
377.83 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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].
| IV (1 mg/kg) | PO (10 mg/kg) | | Tmax (h) | | 0.25 | | Cmax (ng/mL) | 1330 | 1241 | | AUClast (ng/mL?h) | 74.85 | 502.34 | | AUCINF (ng/mL?h) | 75.06 | 503.41 | | T1/2 (h) | 0.13 | | | CL (mL/min/kg) | 222.04 | | | Vss (L/kg) | 1.68 | | | F (%) | | 67 |
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| [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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