Riluzole

Base Information

• Chemical Name: Riluzole
• CAS No.: 1744-22-5
• Molecular Formula: C8H5F3N2OS
• Molecular Weight: 234.202
• Hs Code.: 29342000
• European Community (EC) Number: 605-724-6
• NSC Number: 759823,753433
• UNII: 7LJ087RS6F
• DSSTox Substance ID: DTXSID3045192
• Nikkaji Number: J22.921K
• Wikipedia: Riluzole
• Wikidata: Q415744
• NCI Thesaurus Code: C47704
• RXCUI: 35623
• Pharos Ligand ID: CTLUL57W2GUZ
• Metabolomics Workbench ID: 43044
• ChEMBL ID: CHEMBL744
• Mol file: 1744-22-5.mol

Synonyms:2 Amino 6 trifluoromethoxybenzothiazole;2-Amino-6-trifluoromethoxybenzothiazole;PK 26124;PK-26124;PK26124;Rilutek;Riluzole;RP 54274;RP-54274;RP54274

Chemical Property of Riluzole

Chemical Property:

• Appearance/Colour: white crystalline solid
• Vapor Pressure: 0.00145mmHg at 25°C
• Melting Point: 116-118 °C
• Boiling Point: 296.3 °C at 760 mmHg
• PKA: 2.96±0.10(Predicted)
• Flash Point: 133 °C
• PSA: 76.38000
• Density: 1.572 g/cm³
• LogP: 3.35830
• Storage Temp.: Store at RT
• Solubility.: DMSO: ≥25 mg/mL
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 1
• Exact Mass: 234.00746845
• Heavy Atom Count: 15
• Complexity: 238

Purity/Quality:

99% up, ^*data from raw suppliers

Riluzole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xi
• Hazard Codes: T,Xi
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Amyotrophic Lateral Sclerosis Agents
• Canonical SMILES: C1=CC2=C(C=C1OC(F)(F)F)SC(=N2)N
• Recent ClinicalTrials: Trial of Safety, Tolerability and Efficacy of Trametinib (SNR1611) in Patients With Amyotrophic Lateral Sclerosis (ALS)
• Recent EU Clinical Trials: The glutamate/GABA balance as novel therapeutic target for psychotic and cognitive symptoms in 22q11.2 deletion syndrome
• Recent NIPH Clinical Trials: The clinical trial to assess efficacy of mexiletine for amyotrophic lateral sclerosis
• Description: Riluzole belongs to the derivative of benzothiazole with neuroprotective, potential anti-depressant and anxiolytic activities, which is used in the treatment of a certain type of nerve disease called amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). It is effective to delay the onset of ventilator-dependence or tracheostomy in selected patients, slow down the deterioration of this disease and probably prolong survival by approximately two to three months. Besides, studies have proved that riluzole has anti-depressant activity for refractory depression and serves as an anxiolytic in the treatment of obsessive-compulsive disorder and generalized anxiety disorder. However, riluzole does not cure the ALS and reverse nerve damage or muscle weakness. It is believed to function as an inhibitor of a natural substance called glutamate. It helps protect the nerves in the brain and spinal cord from too much of glutamate which may contribute to the nerve damage. Riluzole is available in both tablet and liquid form. The liquid formulation may be more suitable for patients with swallowing difficulties. Rilutek was launched in Germany, the UK and US (orphan drug status) for treatment of amyotrophic lateral sclerosis (ALS) and is the first drug approved for this indication. A one step synthesis from 4-(trifluoromethoxy)aniline provides a supply of the compound. The source of its neuroprotective and anticonvulsant activity is not clearly understood. It antagonizes excitatory amino acids and blocks presynaptic release of glutamate, is an antagonist of NMDA-induced acetylcholine release and inhibited glutamate and quisqualate induced increases in cGMP but does not bind to NMDA or Kainic receptors. Rilutek has no affinity for glutamate, GABAbenzodiazepine, glycine and adenosine receptors. It easily crosses the blood brain barrier and depresses glutamatergic neurotransmission, stabilizes voltagedependent Na channels in their inactive form and activates G-protein dependent processes.
• Uses: A neuroprotective agent. Modulates glutamatergic transmission. A glutamate release inhibitor. An anticonvulsant. anticonvulsant, glutamate release inhibitor, anti-ALS Labeled Riluzole, intended for use as an internal standard for the quantification of Riluzole by GC- or LC-mass spectrometry. A neuroprotective agent. A glutamate release inhibitor. An anticonvulsant

Technology Process of Riluzole

There total 19 articles about Riluzole 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: 96.0%

ammonium thiocyanate + 4-(trifluoromethoxy)aniline (461-82-5) → Riluzole (1744-22-5)

Guidance literature:

With N,N,N-trimethylbenzenemethanaminium dichloroiodate; In water; dimethyl sulfoxide; at 70 ℃; for 1h;

DOI:10.1016/j.tetlet.2021.153388

Reference yield: 95.0%

4-(trifluoromethoxy)aniline (461-82-5) + potassium thioacyanate (333-20-0) → Riluzole (1744-22-5)

Guidance literature:

With bromine; acetic acid; at 0 - 20 ℃; for 16h; Inert atmosphere;

DOI:10.1002/anie.201504665

Reference yield: 80.0%

4-(trifluoromethoxy)aniline (461-82-5) + ammonium thiocyanate (1147550-11-5) → Riluzole (1744-22-5)

Guidance literature:

With mono(N,N,N-trimethylbenzenaminium) tribromide; In acetonitrile; at 20 ℃; for 24h;

upstream raw materials:

4-(trifluoromethoxy)aniline

ammonium thiocyanate

potassium thioacyanate

tetrabutylammonium thiocyanate

Downstream raw materials:

3-(2-hydroxyethyl)-6-trifluoromethoxy-2-benzothiazoline hydrobromide

3-(3-(2-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-N-(6-(trifluoromethoxy)benzo[d]thiazol-2-yl)propanamide

2-[2-amino-5-(trifluoromethoxy)phenylthio]acetonitrile

C₁₆H₇F₃N₂O₃S

Refernces

• 1、 Pelletier, Jeffrey C.,Velvadapu, Venkata,McDonnell, Mark E.,Wrobel, Jay E.,Reitz, Allen B.. "Intramolecular rearrangement of α-amino acid amide derivatives of 2-aminobenzothiazoles". . p. 4193 - 4195. Retrieved 2014.
• 2、 Mishra, Chandra Bhushan,Kumari, Shikha,Angeli, Andrea,Bua, Silvia,Mongre, Raj Kumar,Tiwari, Manisha,Supuran, Claudiu T.. "Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and in Vitro and in Vivo Investigations". . p. 3100 - 3114. Retrieved 2021/04/12.
• 3、 Chen, Xiran,Fu, Lianrong,Hao, Xin-Qi,Shi, Linlin,Song, Mao-Ping,Zhu, Xinju,Zhu, Yu-Shen. "Iodine-catalyzed amination of benzothiazoles with KSeCN in water to access primary 2-aminobenzothiazoles". supporting information. . Retrieved 2021/09/09.