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134308-13-7 molecular structure
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5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol

ChemBase ID: 208
Molecular Formular: C14H11NO5
Molecular Mass: 273.24084
Monoisotopic Mass: 273.06372246
SMILES and InChIs

SMILES:
O=C(c1cc([N+](=O)[O-])c(O)c(O)c1)c1ccc(cc1)C
Canonical SMILES:
Cc1ccc(cc1)C(=O)c1cc(O)c(c(c1)[N+](=O)[O-])O
InChI:
InChI=1S/C14H11NO5/c1-8-2-4-9(5-3-8)13(17)10-6-11(15(19)20)14(18)12(16)7-10/h2-7,16,18H,1H3
InChIKey:
MIQPIUSUKVNLNT-UHFFFAOYSA-N

Cite this record

CBID:208 http://www.chembase.cn/molecule-208.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol
IUPAC Traditional name
tolcapone
tolcapone (product)
5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol
Brand Name
Tasmar
Synonyms
(3,4-Dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone
Ro-40-7592
Tasmar
(3,4-dihydroxy-5-nitrophenyl)(p-tolyl)methanone
3,4-Dihydroxy-4′-methyl-5-nitrobenzophenone
Ro 40-7592
Tolcapone
Tolcapone
CAS Number
134308-13-7
MDL Number
MFCD00866569
PubChem SID
160963671
46504932
PubChem CID
4659569

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 5.437702  H Acceptors
H Donor LogD (pH = 5.5) 2.9509084 
LogD (pH = 7.4) 1.6083276  Log P 3.2788737 
Molar Refractivity 71.957 cm3 Polarizability 26.861366 Å3
Polar Surface Area 100.67 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 2.63  LOG S -3.68 
Solubility (Water) 5.69e-02 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
Chloroform expand Show data source
DMSO: ≥15 mg/mL expand Show data source
Methanol expand Show data source
Apperance
yellow powder expand Show data source
Yellow Solid expand Show data source
Melting Point
138-140°C expand Show data source
Hydrophobicity(logP)
4 expand Show data source
Storage Condition
-20°C Freezer expand Show data source
desiccated expand Show data source
MSDS Link
Download expand Show data source
Download expand Show data source
Storage Temperature
2-8°C expand Show data source
Target
Transferase expand Show data source
Purity
≥98% (HPLC) expand Show data source
98% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Empirical Formula (Hill Notation)
C14H11NO5 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank - DB00323 external link
Item Information
Drug Groups approved; withdrawn
Description Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT). It is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication. It is a yellow, odorless, non-hygroscopic, crystalline compound. Tolcapone is associated with a risk of hepatotoxicity. [Wikipedia]
Indication Used as an adjunct to levodopa/carbidopa therapy for the symptomatic treatment of Parkinson's Disease. This drug is generally reserved for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies.
Pharmacology Tolcapone is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.
Toxicity LD50 = 1600 mg/kg (Orally in rats)
Affected Organisms
Humans and other mammals
Biotransformation The main metabolic pathway of tolcapone is glucuronidation
Absorption Rapidly absorbed (absolute bioavailability is about 65%)
Half Life 2-3.5 hours
Protein Binding > 99.9% (to serum albumin)
Elimination Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile.
Distribution * 9 L
Clearance * 7 L/h
References
Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [Pubmed]
Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. [Pubmed]
Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. [Pubmed]
Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. [Pubmed]
Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [Pubmed]
External Links
Wikipedia
RxList
PDRhealth
Drugs.com
Sigma Aldrich - SML0150 external link
Biochem/physiol Actions
Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor. It inhibits both central and peripheral COMT. Tolcapone crosses the blood-brain barrier, and has been used for L-DOPA adjunct therapy in the treatment of Parkinson′s Disease.
Toronto Research Chemicals - T535250 external link
Orally active inhibitor of central and peripheral catechol-O-methyltransferase (COMT). Antiparkinsonian.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. Pubmed
  • • Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. Pubmed
  • • Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. Pubmed
  • • Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. Pubmed
  • • Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. Pubmed
  • • Dingemanse, J., et al.: Clin. Pharmacol. Ther., 57, 508 (1995)
  • • Keating, K.A., Drugs, 19, 165 (1995)
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PATENTS

PATENTS

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INTERNET

INTERNET

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