Elafibranor

Base Information

• Chemical Name: Elafibranor
• CAS No.: 923978-27-2
• Molecular Formula: C₂₂H₂₄O₄S
• Molecular Weight: 384.496
• European Community (EC) Number: 815-538-9
• UNII: 2J3H5C81A5
• DSSTox Substance ID: DTXSID601045330
• Wikipedia: Elafibranor
• Wikidata: Q15409440
• NCI Thesaurus Code: C166574
• Pharos Ligand ID: LD5N9FSHLGTT
• Metabolomics Workbench ID: 149413
• ChEMBL ID: CHEMBL3707395
• Mol file: 923978-27-2.mol

Synonyms:2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid;elafibranor;GFT505

Chemical Property of Elafibranor

Chemical Property:

• Boiling Point: 569.0±50.0 °C(Predicted)
• PKA: 3.30±0.11(Predicted)
• PSA: 88.90000
• Density: 1.21±0.1 g/cm3(Predicted)
• LogP: 5.16340
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml).
• XLogP3: 5.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 384.13953042
• Heavy Atom Count: 27
• Complexity: 537

Purity/Quality:

98%,99%, ^*data from raw suppliers

GFT-505 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Canonical SMILES: CC1=CC(=CC(=C1OC(C)(C)C(=O)O)C)C=CC(=O)C2=CC=C(C=C2)SC
• Isomeric SMILES: CC1=CC(=CC(=C1OC(C)(C)C(=O)O)C)/C=C/C(=O)C2=CC=C(C=C2)SC
• Recent ClinicalTrials: A Study to Evaluate the Effect of Food on the Level of Circulating Elafibranor in Healthy Participants After Intake of a Single Tablet
• Recent EU Clinical Trials: A Phase II, Multicenter, Double-Blind, Randomised, Placebo-Controlled Study and Open-Label Long Term Extension to Evaluate the Safety and Efficacy of Elafibranor in Adult Participants with Primary Sclerosing Cholangitis (PSC)
• Description: Elafibranor is an agonist of the peroxisome proliferator-activated receptors (PPAR) α and δ. It increases HDL secretion and expression of the lipid-related genes ABCA1, PLIN2, and ABHD5 in Caco-2/TC7 cells in a PPARα-dependent manner. Elafibranor (10 mg/kg) decreases levels of plasma triglycerides and total cholesterol while increasing plasma HDL and expression of Acox1, a PPARα target gene, in the liver of ApoE2-KI wild-type, but not PPARα knockout, mice fed a Western diet. However, PPARα knockout mice exhibit a decrease in plasma total and non-HDL cholesterol levels, indicating PPARδ has a role in these functions. Elafibranor (30 mg/kg) reduces diet-induced macro- and micro-steatosis in a PPARα-deficient mouse model of non-alcoholic steatohepatitis. It also reduces cholesterol and triglyceride accumulation as well as macrovesicular steatosis in the liver of insulin-resistant db/db mice fed the methionine-choline deficient (MCD) diet. Formulations containing elafibranor are under clinical investigation for the treatment of non-alcoholic steatohepatitis.
• Biological Functions: Elafibranor (GFT505) is an agonist of peroxisome proliferator-activated receptor (PPAR) alpha and delta. EC50 values were 45 and 175 nM, respectively. GFT505 is being developed as a dual PPAR-α/PPAR-δ receptor agonist for the treatment of type 2 diabetes and nonalcoholic fatty liver disease. GFT1007 and GFT505 have an active metabolite, both with potent stimulant activity PPAR-α and to a lesser extent PPAR-δ.

Technology Process of Elafibranor

There total 26 articles about Elafibranor 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: 89.0%

allyl (E)-2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxoprop-1-en-1-yl)phenoxy)-2-methylpropanoate → 2-(2,6-dimethyl-4-{(1E)-3-[4-(methylsulfanyl)phenyl]-3-oxoprop-1-en-1-yl}phenoxy)-2-methylpropanoic acid (824932-88-9,923978-27-2)

Guidance literature:

With water; sodium hydroxide; In N,N-dimethyl-formamide; at 20 ℃; for 22h;

Reference yield: 82.5%

(2E)-3-(4-hydroxy-3,5-dimethylphenyl)-1-[4-(methylsulfanyl)phenyl]prop-2-en-1-one + 2-bromo-2-methylpropionic acid (2052-01-9) → 2-(2,6-dimethyl-4-{(1E)-3-[4-(methylsulfanyl)phenyl]-3-oxoprop-1-en-1-yl}phenoxy)-2-methylpropanoic acid (824932-88-9,923978-27-2)

Guidance literature:

(2E)-3-(4-hydroxy-3,5-dimethylphenyl)-1-[4-(methylsulfanyl)phenyl]prop-2-en-1-one; With sodium hydroxide; In acetonitrile; at 70 ℃; for 1h;

2-bromo-2-methylpropionic acid; In acetonitrile; for 2h; Temperature; Solvent; Reagent/catalyst;

Reference yield: 79.8%

1-[4-methylthiophenyl]-3-[3,5-dimethyl-4-(tertbutyloxycarbonyldimethylmethyloxy)phenyl]prop-2-en-1-one (824932-90-3) → 2-(2,6-dimethyl-4-{3-[4-(methylsulfanyl)phenyl]-3-oxopropen-1-yl}phenoxy)-2-methylpropanoic acid (824932-88-9,923978-27-2)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 - 30 ℃; Concentration; Large scale;

upstream raw materials:

2-bromo-2-methylpropionic acid

4-(Methylthio)acetophenone

ethyl 2-(4-formyl-2,6-dimethylphenoxy)-2-methylpropanoate

4-hydroxy-3,5-dimethylbenzaldehyde

Refernces

• 1、 -. "POLYMORPHS OF ELAFIBRANOR". Page/Page column 23-24. . Retrieved 2021/08/20.
• 2、 -. "NOVEL COMPOUNDS AND THEIR USE IN PREPARATION OF ELAFIBRANOR AND PHARMACEUTICAL ACCEPTABLE SALTS THEREOF". . . Retrieved 2020/03/15.