Ataluren

Base Information

• Chemical Name: Ataluren
• CAS No.: 775304-57-9
• Deprecated CAS: 918899-30-6
• Molecular Formula: C15H9FN2O3
• Molecular Weight: 284.246
• Hs Code.: 2934999090
• European Community (EC) Number: 922-364-8,695-053-5
• UNII: K16AME9I3V
• DSSTox Substance ID: DTXSID5046776
• Nikkaji Number: J2.446.661B
• Wikipedia: Ataluren
• Wikidata: Q753330
• NCI Thesaurus Code: C169791
• Metabolomics Workbench ID: 149373
• ChEMBL ID: CHEMBL256997
• Mol file: 775304-57-9.mol

Synonyms:ataluren;PTC 124;PTC-124;PTC124

Chemical Property of Ataluren

Chemical Property:

• Vapor Pressure: 5.75E-11mmHg at 25°C
• Refractive Index: 1.603
• Boiling Point: 503.7 °C at 760 mmHg
• PKA: 3.58±0.10(Predicted)
• Flash Point: 258.4 °C
• PSA: 76.22000
• Density: 1.379 g/cm³
• LogP: 3.24090
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly)
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 284.05972032
• Heavy Atom Count: 21
• Complexity: 382

Purity/Quality:

PTC-124 - CAS 775304-57-9 - Calbiochem ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC=C(C(=C1)C2=NC(=NO2)C3=CC(=CC=C3)C(=O)O)F
• Recent ClinicalTrials: Ataluren for Nonsense Mutation in CDKL5 and Dravet Syndrome
• Recent EU Clinical Trials: Study of pembrolizumab combined with ataluren in Patients with metastatic pMMR and dMMR colorectal cancer adenocarcinomas or metastatic dMMR endometrial carcinoma: the ATAPEMBRO study.
• Recent NIPH Clinical Trials: An Open-label, Long-Term study of Ataluren in Nonsense Mutation Duchenne Muscular Dystrophy
• Description: Ataluren (PTC124) selectively induces ribosomal read-through of premature but not normal termination codons, with EC50 of 0.1 μM in HEK293 cells, may provide treatment for genetic disorders caused by nonsense mutations (e.g. CF caused by CFTR nonsense mutation). Phase 3. Ataluren is a drug marketed under the trade name Translarna? which was developed by PTC Therapeutics and approved by the European Union in May 2014 for the treatment of Duchenne’s muscular dystrophy (DMD) and potentially other genetic disorders. Ataluren renders ribosomes less sensitive to premature stop or ‘read-through’ codons, which are thought to be beneficial in diseases such as DMD and cystic fibrosis. Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis. PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full length, functional proteins. In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function. The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC50 = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity. Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.
• Uses: Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis. PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full-length, functional proteins. In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function. The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC50 = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity. Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.[Cayman Chemical] PTC-124 is a nonaminoglycoside that has been reported to induce ribosomes to read through premature nonsense stop signals on mRNA, allowing the production of full-length functional proteins,

Technology Process of Ataluren

There total 22 articles about Ataluren 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: 98.0%

3-((5-(2-fluorophenyl))-(1,2,4-oxadiazol-3-yl))benzoic acid methyl ester (775304-60-4) → ataluren (775304-57-9)

Guidance literature:

With lithium hydroxide monohydrate; In 1,4-dioxane; at 25 ℃; for 8.5h; Temperature;

Reference yield: 90.0%

3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzaldehyde → ataluren (775304-57-9)

Guidance literature:

3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzaldehyde; With potassium dihydrogenphosphate; dihydrogen peroxide; In water; acetonitrile; at 20 - 30 ℃;

With sodium chlorite; In water; acetonitrile; at 0 - 30 ℃; for 5h;

Reference yield: 88.4%

3-(N'-((2-fluorobenzoyl)oxy)carbamimidoyl)benzoic acid → ataluren (775304-57-9)

Guidance literature:

In tert-butyl alcohol; at 80 ℃; for 24h;

upstream raw materials:

2-Fluorobenzoyl chloride

3-((5-(2-fluorophenyl))-(1,2,4-oxadiazol-3-yl))benzoic acid methyl ester

3-(N-hydroxycarbamimidoyl)-benzoic acid methyl ester

5-(2-fluorophenyl)-3-(3-methylphenyl)-1,2,4-oxadiazole

Downstream raw materials:

3-((5-(2-fluorophenyl))-(1,2,4-oxadiazol-3-yl))benzoic acid methyl ester

5-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-2-hydroxybenzoic acid

Refernces

• 1、 -. "Method for preparing ataluren". Paragraph 0019; 0028. . Retrieved 2020/09/30.
• 2、 -. "PROCESS FOR PREPARING ATALUREN AND ITS INTERMEDIATES". . . Retrieved 2018/01/18.