Basic information Anti-Parkinson's disease drugs Pharmacokinetics Chemical property Uses Production method Safety Supplier Related
ChemicalBook >  Product Catalog >  API >  Nervous system drugs >  Drug Metabolism in Human Brain >  Entacapone

Entacapone

Basic information Anti-Parkinson's disease drugs Pharmacokinetics Chemical property Uses Production method Safety Supplier Related

Entacapone Basic information

Product Name:
Entacapone
Synonyms:
  • (E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-pmpenamide
  • Entacapone (150 mg)
  • (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enaMide
  • 2-PropenaMide,2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-, (2E)-
  • (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylacrylamide
  • Entacapone (isomer E)
  • (E)-2-cyano-3-(5-(dihydroxyamino)-3,4-dioxocyclohexa-1,5-dienyl)-N,N-diethylacrylamide
  • ENTACAPONE
CAS:
130929-57-6
MF:
C14H15N3O5
MW:
305.29
EINECS:
212-686-0
Product Categories:
  • Histone Methyltransf
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
Mol File:
130929-57-6.mol
More
Less

Entacapone Chemical Properties

Melting point:
162-1630C
Boiling point:
526.6±50.0 °C(Predicted)
Density 
1.392±0.06 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
DMSO: soluble20mg/mL, clear
pka
pKa ~4.5(at 25℃)
form 
powder
color 
white to light brown
InChIKey
JRURYQJSLYLRLN-BJMVGYQFSA-N
CAS DataBase Reference
130929-57-6(CAS DataBase Reference)
More
Less

Safety Information

WGK Germany 
3
HS Code 
2926900005
Hazardous Substances Data
130929-57-6(Hazardous Substances Data)
More
Less

Entacapone Usage And Synthesis

Anti-Parkinson's disease drugs

Entacapone is an anti-Parkinson's disease drug which is successfully developed by Orion Pharma company in Swedish. It is a highly selective potent catechol-O-methyltransferase (COMT) inhibitor, rarely penetrating the blood-brain barrier, and primarily acting in the intestinal tract. It is dose-dependent to decrease levels of 3-OMD in serum and the brain, increasing levodopa, dopamine and DOPAC levels in the brain and significantly reducing the dose which is required to increase dopamine concentration in striatal. Levodopa and carbidopa combining with COMTI can significantly increase the bioavailability of levodopa (3-4 times). Activity of COMTI in red blood cell is reversible. When in 800mg dose, the maximum inhibitory activity is up to 82%, so Entacapone combines with levodopa and carbidopa, which can be used for adjuvant therapy of idiopathic Parkinson's disease.

Pharmacokinetics

This product is rapid oral absorption, the bioavailability is a dose-dependent with the range of 30% to 45%. In the range of 5~800 mg, pharmacokinetics of Entacapone (abbreviation: Ent) is linear, peak plasma concentration is related to AUC and dose. Food does not affect the absorption of this product, 98% Ent combines with plasma albumin, rarely distributing in tissues. In patients with Parkinson disease (abbreviated: PD), and is required to take levodopa/carbidopa, the peak concentration of Ent arrives within 1~2h. The rate of Ent through the blood-brain barrier is low, the plasma elimination half-life is 1.5~3.5h. After oral administration, Ent (E-configuration) is metabolized to Z-isomer in the blood and is present in plasma and red blood cells. Z-isomer has little impact on the clinical efficacy. Its drug-time curve is similar to Ent. Z-Ent accounts for about 5% of the total AUC. Ent and Z-Ent are acidified by glucose in the liver. After metabolism of Ent: 10% excreted in the urine, 90% of Ent excreted in the feces, only 0.2% excreted in the urine in phony drugs. While taking levodopa in PD patients, and oral Ent 200 mg after elimination half-life of about 1 h, the body has no savings.
Pharmacokinetic study shows that in healthy persons and patients with PD, Ent can increase the bioavailability of levodopa. In the short-term PD patients taking Ent, AUC of levodopa increase 25%, while the long-term taking Ent can increase 50%. AUC of 3-OMD relatively reduces 60%. In these studies, they found that plasma peak time of levodopa will be extended. Single dose of Entacapone (while not taking levodopa/carbidopa), in patients with liver disease, the patient's AUC and Cmax is 2 times of the patients with normal liver function. We should adjust the dosage of the patient. In patients with mild to moderate kidney disease, it is not necessary to adjust the dosage. Kidney patients receiving dialysis can extend dosing interval.
The above information is edited by the Chemicalbook of Liu Yujie.

Chemical property

Crystals, melting point 162--163 ℃.

Uses

As COMT inhibitors, it is used to treat Parkinson's disease.

Production method

1.83 g 3,4-dihydroxy-5-nitrobenzaldehyde and 1.5g N, N-diethyl-cyanoacetamide and a catalytic amount of piperidine acetate are dissolved in 40ml of dry ethanol , followed by stirring overnight , 2.23 g crude product is obtained, yield 73%, melting point 153~156 ℃.
Heated at 90 ℃, the 3.0 kg crude product is dissolved in 8.0kg acetic acid (or formic acid) containing 80 g HBr (or 40gHCl).It is slowly cooled to 20 ℃, and stirred at this temperature for 20h, then at 15 ℃ stirred for 6h. The precipitated crystals were collected by filtration, carefully washed with cool (4 ℃) 1L toluene-acetic acid (1: l v/v) mixed solution, and washed with 1L cold toluene. It is dried at 45 ℃under vacuum and 2.4kg crystalline pure Entacapone is obtained, yield 80%, melting point 162-163 ℃.

Description

Entacapone was introduced in Finland, Germany and Sweden as an adjunctive treatment with L-dopa in Parkinson’s disease. Entacapone is the second drug in its class to reach the market; it can be obtained by basecatalyzed condensation of the corresponding benzaldehyde with a cyanoacetamide. Entacapone is a highly selective and orally-active catechol-0- methyltransferase (COMT) inhibitor ; by inhibiting metabolism of L-dopa when given as an adjuvant in patients with Parkinson’s disease, Entacapone markedly prolongs the effects of L-dopa and improves its bioavailability. Results from clinical studies showed that 200mglday Entacapone coadministered with L-dopa lowered the dose of the latter required to reduce fluctuations in motor performance.

Chemical Properties

Yellow Crystalline Solid

Originator

Orion Pharma (Finland)

Uses

(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

Uses

antiparkinsinian;catechol-O-methyl transferase inhibitor

Uses

This compound belongs to the cinnamic acid amides. These are amides of cinnamic acids. 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-

Definition

ChEBI: A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5 nitrophenyl group.

Manufacturing Process

N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide (2- Propenamide, 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl).
A solution containing 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde, 1.5 g of N,N-diethylcyanoacetamide and catalytic amount of piperidine acetate in 40 ml of dry ethanol was refluxed over night. After cooling the solvent was evaporated in vacuo and the residue was recrystallized from waterdimethylformamide. Yield of desired product was 2.23 g (73%), melting point 153°-156°C.

brand name

Comtan(Orion);Comtess.

Therapeutic Function

Antiparkinsonian

General Description

Entacapone, (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide (Comtan),is a nitrocatechol that is practically insoluble in water (pKa=4.50). Entacapone is rapidly absorbed after oral administrationand does not cross the BBB. Entacapone does not distributewidely into tissues because of its high plasma proteinbinding and it is completely metabolized before excretion.The main metabolic pathway is by isomerization to the cisisomerfollowed by direct glucuronidation of the parent andthe cis-isomer. The glucuronide conjugates are inactive.Entacapone is eliminated in the feces (90%) and urine (10%).Entacapone is indicated as an adjunct to levodopa/carbidopato treat patients with idiopathic PD who experience the signsand symptoms of end-of-dose wearing off.

Biochem/physiol Actions

Entacapone is a catechol-O-methyl transferase (COMT) inhibitor. Used in treatment of Parkinson′s disease, entacapone is administered with L-DOPA to inihibit COMT from converting L-DOPA into a compound that cannot cross the blood brain barrier.

Entacapone Preparation Products And Raw materials

Raw materials

EntacaponeSupplier

Hunan Kaimir Biotechnology Co., Ltd. Gold
Tel
0731-89714511
Email
sales@chemapi.com.cn
Hubei Zhongshan Medical Technology Co., Ltd Gold
Tel
027-61907345-
Email
w13397111514@163.com
J & K SCIENTIFIC LTD.
Tel
010-82848833- ;010-82848833-
Email
jkinfo@jkchemical.com;market6@jkchemical.com
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801
Email
3bsc@sina.com
Chembest Research Laboratories Limited
Tel
021-20908456-
Email
sales@BioChemBest.com