(2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide

• ChemBase ID: 377
• Molecular Formular: C14H15N3O5
• Molecular Mass: 305.286
• Monoisotopic Mass: 305.1011706
• SMILES: O=C(N(CC)CC)/C(=C/c1cc([N+](=O)[O-])c(O)c(O)c1)/C#N
• Canonical SMILES: CCN(C(=O)/C(=C/c1cc(O)c(c(c1)[N+](=O)[O-])O)/C#N)CC
• InChI: InChI=1S/C14H15N3O5/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9/h5-7,18-19H,3-4H2,1-2H3/b10-5+
• InChIKey: JRURYQJSLYLRLN-BJMVGYQFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
• IUPAC Traditional name: entacapone
• Brand Name: Comtan; Comtess
• Synonyms: Entacapona [INN-Spanish]; Entacapone [Usan:Inn]; Entacaponum [INN-Latin]; entacapone; Entacapone; (2E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide; OR-611; Comtan; Comtess

Database IDs

• CAS Number: 130929-57-6
• PubChem SID: 46508734; 160963840
• PubChem CID: 5281081

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.940143
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 1.5019009
• LogD (pH = 7.4): 0.26901695
• Log P: 1.6348238
• Molar Refractivity: 79.5086 cm^3
• Polarizability: 29.130468 Å^3
• Polar Surface Area: 127.7 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.5
• LOG S: -3.58
• Solubility (Water): 7.97e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol
• Apperance: Yellow Solid
• Melting Point: 162-163°C
• Hydrophobicity(logP): 2.8

Safety Information

• Storage Condition: -20°C Freezer

Pharmacology Properties

• Target: Others

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB00494

• Drug Groups: approved; investigational
• Description: Entacapone is a selective, reversible catechol-O-methyl transferase (COMT) inhibitor for the treatment of Parkinson's disease. It is a member of the class of nitrocatechols. When administered concomittantly with levodopa and a decarboxylase inhibitor (e.g., carbidopa), increased and more sustained plasma levodopa concentrations are reached as compared to the administration of levodopa and a decarboxylase inhibitor.
• Indication: Used as an adjunct to levodopa / carbidopa in the symptomatic treatment of patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose "wearing-off".
• Pharmacology: Entacapone is structurally and pharmacologically related to tolcapone, but unlike tolcapone, is not associated with hepatotoxicity. Entacapone is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. 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, and 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 the it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.
• Toxicity: Side effect include increase the occurrence of orthostatic hypotension, severe rhabdomyolysis, dyskinesia, hallucinations, hyperkinesia, hypokinesia, dizziness, fatigu,e gastrointestinal effects including abdominal pain constipation diarrhea nausea
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolized via isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer.
• Absorption: Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
• Half Life: 0.4-0.7 hour
• Protein Binding: 98% (bind to serum albumin)
• Elimination: Entacapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug.
• Distribution: * 20 L
• Clearance: * 850 mL/min
• References: Najib J: Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771. [Pubmed] ; Chong BS, Mersfelder TL: Entacapone. Ann Pharmacother. 2000 Sep;34(9):1056-65. [Pubmed] ; Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M: Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002 Apr;105(4):245-55. [Pubmed] ; Brooks DJ, Sagar H: Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1071-9. [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; Drugs.com

Toronto Research Chemicals - E558500

(E)-Isomer of Entacapone polymorphic form A. Peripherally acting inhibitor of catechol-O-methyl transferase (COMT), an enzyme involved in the metabolism of catecholamine neurotransmitters and related drugs. Antiparkinsonian.

REFERENCES

• Najib J: Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771. Pubmed
• Chong BS, Mersfelder TL: Entacapone. Ann Pharmacother. 2000 Sep;34(9):1056-65. Pubmed
• Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M: Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002 Apr;105(4):245-55. Pubmed
• Brooks DJ, Sagar H: Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1071-9. 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
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