Tolrestat

Base Information

• Chemical Name: Tolrestat
• CAS No.: 82964-04-3
• Molecular Formula: C₁₆H₁₄F₃NO₃S
• Molecular Weight: 357.353
• UNII: 0T93LG5NMK
• DSSTox Substance ID: DTXSID80904890
• Nikkaji Number: J23.281E
• Wikipedia: Tolrestat
• Wikidata: Q7814620
• NCI Thesaurus Code: C96310
• Pharos Ligand ID: 2WDT8XKGW4Q6
• Metabolomics Workbench ID: 52483
• ChEMBL ID: CHEMBL436
• Mol file: 82964-04-3.mol

Synonyms:AY 27773;AY-27,773;N-((5-(trifluoromethyl)-6-methoxy-1-naphthalenyl)thioxomethyl)-N-methylglycine;N-5-trifluoromethyl-6-methoxy-1-thionaphthoyl-N-methylglycine;tolrestat

Chemical Property of Tolrestat

Chemical Property:

• Vapor Pressure: 9.69E-11mmHg at 25°C
• Melting Point: 164-165°
• Refractive Index: 1.601
• Boiling Point: 498.1 °C at 760 mmHg
• PKA: 3.49±0.10(Predicted)
• Flash Point: 255 °C
• PSA: 81.86000
• Density: 1.399 g/cm³
• LogP: 3.55910
• Storage Temp.: 2-8°C
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly)
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 357.06464897
• Heavy Atom Count: 24
• Complexity: 486

Purity/Quality:

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

Tolrestat ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(CC(=O)O)C(=S)C1=CC=CC2=C1C=CC(=C2C(F)(F)F)OC
• Description: Tolrestat is a long-acting aldose reductase inhibitor reportedly useful in the prophylaxis of diabetic neuropathy, retinopathy and cataracts. Tolrestat is an aldose reductase inhibitor (IC50 = 35 nM for the bovine lens enzyme). Dietary administration of tolrestat decreases sciatic nerve galactitol accumulation in a rat model of galactosemia (ED50 = 7.3 mg/kg per day) and sciatic nerve sorbitol accumulation (ED50 = 4.8 mg/kg per day) in a rat model of diabetes induced by streptozotocin (STZ; ). It also decreases urinary total protein exretion in a rat model of STZ-induced diabetes when administered at a dose of 25 mg/kg per day. Topical administration of tolrestat (2 and 3% in 10 μl four times per day) decreases levels of galactitol in the lens of and inhibits cataract formation in rats fed a high-galactose diet.
• Uses: Tolrestat is an aldose reductase inhibitor. Alredase (Wyeth-Ayerst).

Technology Process of Tolrestat

There total 11 articles about Tolrestat 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:

6-methoxy-1-naphthalenecarboxylic acid methyl ester (61109-48-6) → tolrestat (120522-86-3,120522-87-4,82964-04-3)

Guidance literature:

Multi-step reaction with 7 steps

1: 87 percent / I₂, HIO₃, H₂SO₄ / acetic acid

2: 93 percent / Cu / pyridine / 20 h / 120 °C

3: hydrolysis

4: SOCl₂

6: P₂S₅ / Heating

7: KOH

With potassium hydroxide; thionyl chloride; tetraphosphorus decasulfide; sulfuric acid; iodine; iodic acid; copper; In pyridine; acetic acid;

DOI:10.1021/jm00369a003

Reference yield:

5-iodo-6-methoxy-1-naphthalenecarboxylic acid methyl ester (84532-68-3) → tolrestat (120522-86-3,120522-87-4,82964-04-3)

Guidance literature:

Multi-step reaction with 6 steps

1: 93 percent / Cu / pyridine / 20 h / 120 °C

2: hydrolysis

3: SOCl₂

5: P₂S₅ / Heating

6: KOH

With potassium hydroxide; thionyl chloride; tetraphosphorus decasulfide; copper; In pyridine;

DOI:10.1021/jm00369a003

Reference yield:

5-Methyl-2-methoxy-1-(trifluoromethyl)naphthalene (85674-78-8) → tolrestat (120522-86-3,120522-87-4,82964-04-3)

Guidance literature:

Multi-step reaction with 5 steps

1: 55 percent / KMnO₄

2: SOCl₂

4: P₂S₅ / Heating

5: KOH

With potassium hydroxide; potassium permanganate; thionyl chloride; tetraphosphorus decasulfide;

DOI:10.1021/jm00369a003

upstream raw materials:

tolrestat methyl ester

6-methoxy-1-naphthalenecarboxylic acid methyl ester

5-Methyl-2-methoxy-1-(trifluoromethyl)naphthalene

6-methoxy-5-(trifluoromethyl)-1-naphthalenecarboxylic acid

Downstream raw materials:

6-methoxy-5-(trifluoromethyl)-1-naphthalenecarboxylic acid

N-<<6-methoxy-5-(trifluoromethyl)-1-naphthalenyl>oxomethyl>-N-methylglycine

5-(Carboxymethyl-methyl-carbamoyl)-2-methoxy-naphthalene-1-carboxylic acid

N-<(5-carboxyl)-6-methoxy-1-naphtalenyl>-thiomethyl-N-methylglycine

Refernces

• 1、 Sestanj,Bellini,Fung,Abraham,Treasurywala,Humber,Simard-Duquesne,Dvornik. "N-[[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl]thioxomethyl]-N-methylgl ycine (Tolrestat), a potent, orally active aldose reductase inhibitor". . p. 255 - 256. Retrieved 2007/10/02.