GNE 7915

Base Information

• Chemical Name: GNE 7915
• CAS No.: 1351761-44-8
• Molecular Formula: C₁₉H₂₁F₄N₅O₃
• Molecular Weight: 443.401
• Mol file: 1351761-44-8.mol

Synonyms:GNE-7915

Chemical Property of GNE 7915

Chemical Property:

• Melting Point: 143 - 144°C
• Boiling Point: 629.9±65.0 °C(Predicted)
• PKA: 2.80±0.10(Predicted)
• Density: 1.404±0.06 g/cm3(Predicted)
• Solubility.: Chloroform (Slightly), DMSO (Slightly)

Purity/Quality:

98% min ^*data from raw suppliers

GNE 7915 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Uses: Leucine-rich repeat kinase 2 (LRRK2) is an enzyme that interacts with parkin, a ligase that is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Loss of function of the parkin protein leads to dopaminergic cell death. The development of Parkinson's disease has been strongly associated with mutations in the LRRK2 gene that lead to increased kinase activity. GNE-7915 is a selective, brain-penetrable LRRK2 inhibitor (Kis = 2 and 18.7 nM in biochemical and cell-based assays, respectively). It inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation with an IC50 value of 20 nM in vivo.[Cayman Chemical] GNE-7915 is a Blood-Brain Barrier (BBB) penetrable small molecule inhibitor of Leucine-Rich Repeat Kinase 2 (LRRK2).

Technology Process of GNE 7915

There total 11 articles about GNE 7915 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 40.0%

morpholine (110-91-8,99108-56-2) + 4‐((4‐(ethylamino)‐5‐(trifluoromethyl)pyrimidin‐2‐yl)amino)‐2‐fluoro‐5‐methoxybenzoic acid (1401423-43-5) → GNE-7915 (1351761-44-8)

Guidance literature:

4‐((4‐(ethylamino)‐5‐(trifluoromethyl)pyrimidin‐2‐yl)amino)‐2‐fluoro‐5‐methoxybenzoic acid; With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; In chloroform; at 20 ℃;

morpholine; In chloroform; for 2h; Reflux;

DOI:10.1002/cmdc.202000872

Reference yield:

2-chloro-N-ethyl-5-(trifluoromethyl)pyrimidin-4-amine (1374829-47-6) → GNE-7915 (1351761-44-8)

Guidance literature:

Multi-step reaction with 2 steps

1: toluene-4-sulfonic acid / 1,4-dioxane / 2 h / 100 °C

2: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 1 h / 0 - 20 °C

With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; toluene-4-sulfonic acid; N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; dichloromethane;

DOI:10.1021/jm301020q

Reference yield:

4-amino-2-fluoro-5-methoxy-benzoic acid (1001346-91-3) → GNE-7915 (1351761-44-8)

Guidance literature:

Multi-step reaction with 2 steps

1: toluene-4-sulfonic acid / 1,4-dioxane / 2 h / 100 °C

2: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 1 h / 0 - 20 °C

With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; toluene-4-sulfonic acid; N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; dichloromethane;

DOI:10.1021/jm301020q

upstream raw materials:

(2-chloro-5-iodo-pyrimidin-4-yl)-ethyl-amine

2-chloro-N-ethyl-5-(trifluoromethyl)pyrimidin-4-amine

4-amino-2-fluoro-5-methoxy-benzoic acid

morpholine

Refernces

• 1、 Estrada, Anthony A.,Liu, Xingrong,Baker-Glenn, Charles,Beresford, Alan,Burdick, Daniel J.,Chambers, Mark,Chan, Bryan K.,Chen, Huifen,Ding, Xiao,Dipasquale, Antonio G.,Dominguez, Sara L.,Dotson, Jennafer,Drummond, Jason,Flagella, Michael,Flynn, Sean,Fuji, Reina,Gill, Andrew,Gunzner-Toste, Janet,Harris, Seth F.,Heffron, Timothy P.,Kleinheinz, Tracy,Lee, Donna W.,Le Pichon, Claire E.,Lyssikatos, Joseph P.,Medhurst, Andrew D.,Moffat, John G.,Mukund, Susmith,Nash, Kevin,Scearce-Levie, Kimberly,Sheng, Zejuan,Shore, Daniel G.,Tran, Thuy,Trivedi, Naimisha,Wang, Shumei,Zhang, Shuo,Zhang, Xiaolin,Zhao, Guiling,Zhu, Haitao,Sweeney, Zachary K.. "Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors". . p. 9416 - 9433. Retrieved 2013/01/16.