Tolcapone

Base Information

• Chemical Name: Tolcapone
• CAS No.: 134308-13-7
• Molecular Formula: C14H11NO5
• Molecular Weight: 273.245
• Hs Code.: 2914710000
• European Community (EC) Number: 694-343-9
• UNII: CIF6334OLY
• ChEMBL ID: CHEMBL1324
• DSSTox Substance ID: DTXSID3023685
• Metabolomics Workbench ID: 42708
• NCI Thesaurus Code: C47762
• Nikkaji Number: J459.846F
• Pharos Ligand ID: DWDDYTUXCFFS
• RXCUI: 72937
• Wikidata: Q413840
• Wikipedia: Tolcapone
• Mol file: 134308-13-7.mol

Synonyms:3,4 Dihydroxy 5' methyl 5 nitrobenzophenone;3,4-dihydroxy-5'-methyl-5-nitrobenzophenone;Ro 40 7592;Ro 40-7592;Ro 407592;Ro-40-7592;Ro407592;SOM0226;Tasmar;tolcapone

Chemical Property of Tolcapone

Chemical Property:

• Vapor Pressure: 4.72E-10mmHg at 25°C
• Melting Point: 126-128 °C
• Refractive Index: 1.661
• Boiling Point: 485.6 °C at 760 mmHg
• PKA: 4.78±0.38(Predicted)
• Flash Point: 205.8 °C
• PSA: 103.35000
• Density: 1.419 g/cm³
• LogP: 3.06860
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: ≥15mg/mL
• XLogP3: 3.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 273.06372245
• Heavy Atom Count: 20
• Complexity: 372

Purity/Quality:

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

Tolcapone ≥99%(HPLC) ^*data from reagent suppliers

Safty Information:

• Pictogram(s): N
• Hazard Codes: N
• Statements: 50
• Safety Statements: 61

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Parkinson Disease Agents
• Canonical SMILES: CC1=CC=C(C=C1)C(=O)C2=CC(=C(C(=C2)O)O)[N+](=O)[O-]
• Recent ClinicalTrials: Trial of Tolcapone With Oxaliplatin for Neuroblastoma
• Recent EU Clinical Trials: Randomized, controlled trial of the effectiveness of add-on tolcapone to usual antipsychotic therapy on cognitive and negative symptoms of patients with schizophrenia genotyped for COMT polymorphisms
• Recent NIPH Clinical Trials: Clinical study of tolcapone for transthyretin (TTR)-type cerebral amyloid angiopathy in patients with familial amyloid polyneuropahty (FAP)
• Description: Tolcapone (134308-13-7) is a catechol O-methyltransferase inhibitor (COMT), inhibiting both brain and peripheral enzymes.1?Potent inhibitor of alpha-synuclein and beta-amyloid oligomerization and fibrillogenesis protecting against extracellular toxicity.2?Binds to transthyretin (TTR) with high affinity (21 to 58 nM) and inhibits TTR aggregation in human plasma and prevents TTR-induced cytotoxicity?in vitro. Stabilizes TTR in mice and humans?in vivo.3?Inhibits O-methylation of exogenous polyphenols such as EGCG.4?Cell permeable. Orally bioavailable.
• Uses: Orally active inhibitor of central and peripheral catechol-O-methyltransferase (COMT). Antiparkinsonian Tolcapone may be used in COMT-mediated cell signaling studies.Tolcapone has been used in methyltransferase assay in human embryonic kidney 293 cells.
• Therapeutic Function: Antiparkinsonian
• Clinical Use: Catechol-o-methyltransferase inhibitor: Treatment of Parkinson’s disease
• Drug interactions: Potentially hazardous interactions with other drugs Antidepressants: avoid with MAOIs.

Technology Process of Tolcapone

There total 2 articles about Tolcapone 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: 91.0%

3-O-Methyltolcapone (134612-80-9) → tolcapone (134308-13-7)

Guidance literature:

With pyridine; aluminium trichloride; In ethyl acetate; for 2h; Heating;

DOI:10.1080/00397910701821077

Reference yield: 67.0%

C14H12O3 (1391053-03-4) → tolcapone (134308-13-7)

Guidance literature:

With 3-(ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium bis(trifluoromethanesulfonyl)imide; at 20 ℃; for 2h; Ionic liquid;

DOI:10.1016/j.tetlet.2019.151529

Reference yield: 95.0%

acetic anhydride (108-24-7) + tolcapone (134308-13-7) → 5-N-acetylamino-3,4-dihydroxy-4'-methyl-benzophenone

Guidance literature:

acetic anhydride; tolcapone; With pyridine; In acetonitrile; at 25 ℃; for 2h;

With cyclohexene; palladium on activated charcoal; In ethanol; ethyl acetate; for 4h; Heating;

DOI:10.1021/tx025569n

upstream raw materials:

3-O-Methyltolcapone

C₁₄H₁₂O₃

Refernces

• 1、 Chaudhary, Renu,Natarajan, Palani,Rani, Neetu,Sakshi,Venugopalan, Paloth. "3-(Ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium cation: A green alternative to tert-butyl nitrite for synthesis of nitro-group-containing arenes and drugs at room temperature". supporting information. . Retrieved 2019/12/30.