1351758-81-0

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
• CAS NO: 1351758-81-0
• Molecular Formula: C₁₇H₂₀ClN₅O₃
• Molecular Weight: 377.8254
• Product Categories: Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Amines, Aromatics, Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 1351758-81-0.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 641.1±65.0 °C(Predicted)
• Appearance: /
• Density: 1.381±0.06 g/cm3(Predicted)
• Solubility: insoluble in H2O; ≥18.9 mg/mL in DMSO; ≥7.64 mg/mL in EtOH with ultrasonic
• PKA: 4.60±0.10(Predicted)
• CAS DataBase Reference: [4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone(CAS DataBase Reference)
• NIST Chemistry Reference: [4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone(1351758-81-0)
• EPA Substance Registry System: [4-[[5-Chloro-4-(MethylaMino)-2-pyriMidinyl]aMino]-3-Methoxyphenyl]-4-MorpholinylMethanone(1351758-81-0)

Safety Data

• Hazardous Substances Data: 1351758-81-0(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 1351758-81-0 differently. You can refer to the following data:
1. [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.
2. [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.

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.

Upstream product

• 761440-55-5 (3-methoxy-4-nitrophenyl)(morpholino)methanone 
• 5081-36-7 3-methoxy-4-nitrobenzoic acid 
• 2486-69-3 3-methoxy-4-aminobenzoic acid 
• 940927-35-5 2-chloro-5-chloro-N-methylpyrimidin-4-amine 

Downstream Products

• 1351759-76-6 [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-hydroxy-phenyl]-morpholin-4-yl-methanone 

Relevant articles and documents

Brain penetrant LRRK2 inhibitor

Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here, we report that a 2-anilino-4-methylamino-5- chloropyrimidine, HG-10-102-01

Discovery of selective LRRK2 inhibitors guided by computational analysis and molecular modeling

Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent and selective small molecules capable of inhibiting the kinase activity of LRRK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.