6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

• ChemBase ID: 620
• Molecular Formular: C8H5F3N2OS
• Molecular Mass: 234.1983096
• Monoisotopic Mass: 234.00746845
• SMILES: s1c2c(nc1N)ccc(OC(F)(F)F)c2
• Canonical SMILES: Nc1nc2c(s1)cc(cc2)OC(F)(F)F
• InChI: InChI=1S/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)
• InChIKey: FTALBRSUTCGOEG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
• IUPAC Traditional name: riluzole; 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
• Brand Name: Rilutek; Riluzole HCl
• Synonyms: riluzole; Riluzole; 2-Amino-6-(trifluoromethoxy)benzothiazole; 6-Trifluoromethoxy-benzothiazol-2-ylamine; 6-(Trifluoromethoxy)-2-benzothiazolamine; 6-(Trifluoromethoxy)-2-aminobenzothiazole; 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine; 6-(trifluoromethoxy)benzo[d]thiazol-2-amine; 2-Amino-6-trifluoro-methoxybenzothiazole; 2-Amino-6-(trifluoromethoxy)benzothiazole; Riluzole; PK-26124; RP-54274; Rilutek; Riluzole(Rilutek); 6-(Trifluoromethoxy)-1,3-benzothiazol-2-amine; 2-Amino-6-(trifluoromethoxy)-1,3-benzothiazole 97%

Database IDs

• CAS Number: 1744-22-5
• MDL Number: MFCD00210213
• PubChem SID: 24278006; 46508094; 160964083
• PubChem CID: 5070

CALCULATED PROPERTIES

JChem

• Acid pKa: 16.440592
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 3.353241
• LogD (pH = 7.4): 3.3992848
• Log P: 3.3999074
• Molar Refractivity: 44.3727 cm^3
• Polarizability: 18.69663 Å^3
• Polar Surface Area: 48.14 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.83
• LOG S: -3.77
• Solubility (Water): 3.95e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: ≥25 mg/mL
• Apperance: white solid; White Solid
• Melting Point: 108-110°C; 114 - 116°C; 117°C; 119°C
• Hydrophobicity(logP): 2.3; 3.235

Safety Information

• Storage Condition: -20°C; Hygroscopic, Refrigerator, Under Inert Atmosphere; Room Temperature (15-30°C)
• Storage Warning: TOXIC; Toxic
• RTECS: DL2830000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 25
• Safety Statements: 45
• TSCA Listed: false
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H301
• GHS Precautionary statements: P301 + P310
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3

Pharmacology Properties

• Gene Information: rat ... Scnn1g(24768)
• Mechanism of Action: Glutamate transporter activation; High-voltage calcium channel blockade; N-methyl-D-aspartate (NMDA)/glutamate receptor antagonism; Sodium channel blockade

Product Information

• Purity: 95%; 96%; 97%
• Salt Data: Free Base
• Application(s): Anticonvulsant, antiepileptic agent; Used in treatment of amyotrophic lateral sclerosis
• Empirical Formula (Hill Notation): C8H5F3N2OS

DETAILS

MP Biomedicals - 02193713

A glutamate release inhibitor which also blocks voltage-dependent Na^+ channels and inhibits GABA uptake.

DrugBank - DB00740

• Drug Groups: approved; investigational
• Description: A glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem]
• Indication: For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)
• Pharmacology: Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.
• Affected Organisms: Humans and other mammals
• Biotransformation: Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans.
• Absorption: Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%.
• Half Life: The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
• Protein Binding: 96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.
• References: Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. [Pubmed] ; Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. [Pubmed] ; van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ: Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3. [Pubmed] ; Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. [Pubmed] ; Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. [Pubmed] ; Lamanauskas N, Nistri A: Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur J Neurosci. 2008 May;27(10):2501-14. Epub 2008 Apr 26. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1614

Research Area: Neurological Disease
Biological Activity:
Riluzole(Rilutek) is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase the survival approximately 3–5 months. [1] Its pharmacological activities in motor neurons include the following: 1) an inhibitory effect on glutamate release 2) inactivation of voltage-dependent sodium channels  3) interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. In animal models, this agent has been shown to exhibit myorelaxant and sedative activities, apparently due to the blockade of glutamatergic neurotransmission. [1]

Sigma Aldrich - R116

Biochem/physiol Actions
Glutamate release inhibitor; anticonvulsant

Sigma Aldrich - R3772

Biochem/physiol Actions
Glutamate release inhibitor

Toronto Research Chemicals - R510000

A neuroprotective agent. Modulates glutamatergic transmission. A glutamate release inhibitor. An anticonvulsant.

REFERENCES

• Mantz, et al., Eur. J. Pharmacol. , 257 : R7, (1994).
• Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. Pubmed
• Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. Pubmed
• van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ: Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3. Pubmed
• Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. Pubmed
• Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. Pubmed
• Lamanauskas N, Nistri A: Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur J Neurosci. 2008 May;27(10):2501-14. Epub 2008 Apr 26. Pubmed
• http://en.wikipedia.org/wiki/Riluzole
• Mizoule, J., et al.: Neuropharmacology, 24, 767 (1985)
• Wahl, F., et al.: Eur. J. Pharmacol., 230, 209 (1993) Bensimon, G., et al.: N. Engl. J. Med., 330, 585 (1994)
• Yagupol'skii, L.M. et al., Zh. Obshch. Khim., 1963, 33, 2301, (synth)
• Eur. Pat., 1982, Pharmindustrie, 50 551; CA, 97, 44352, (pharmacol)
• Mizoule, J. et al., Neuropharmacology, 1985, 24, 767, (pharmacol)
• Tsai, C. et al., Neurol. Neurobiol., 1987, 24, 79, (pharmacol)
• Mantz, J. et al., Eur. J. Pharmacol., 1994, 257, R7, (pharmacol)
• Bensimon, G. et al., N. Engl. J. Med., 1994, 330, 585, (clin trial)
• Rowland, L.P., N. Engl. J. Med., 1994, 330, 636
• Mantz, J., CNS Drug Rev., 1996, 2, 40, (rev)