Entacapone

Bezeichnung:Entacapone

CAS-Nr130929-57-6

Englisch Name:Entacapone

CBNumberCB5726435

SummenformelC14H15N3O5

Molgewicht305.29

MOL-Datei130929-57-6.mol

Entacapone physikalisch-chemischer Eigenschaften

Schmelzpunkt	162-1630C
Siedepunkt	526.6±50.0 °C(Predicted)
Dichte	1.392±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: soluble20mg/mL, clear
Aggregatzustand	powder
pka	pKa ~4.5(at 25℃)
Farbe	white to light brown
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
InChIKey	JRURYQJSLYLRLN-BJMVGYQFSA-N
CAS Datenbank	130929-57-6(CAS DataBase Reference)

Sicherheit

WGK Germany	3
HS Code	2926900005
Giftige Stoffe Daten	130929-57-6(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Entacapone Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
Yellow Crystalline Solid
Originator
Orion Pharma (Finland)
Verwenden
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-
Verwenden
antiparkinsinian;catechol-O-methyl transferase inhibitor
Verwenden
(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
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.
Trademarks
Comtan(Orion);Comtess.
Therapeutic Function
Antiparkinsonian
Allgemeine Beschreibung
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 (pK_a＝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.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Anticoagulants: enhances anticoagulant effect of warfarin
Antidepressants: use with caution in combination with moclobemide, tricyclics and venlafaxine; avoid with MAOIs.
Dopaminergics: possibly enhances effects of apomorphine; possibly reduces concentration of rasagiline; max dose of selegiline is 10 mg in combination.
Stoffwechsel
Entacapone undergoes extensive first-pass metabolism to form glucuronide metabolites.
It is eliminated mainly in the faeces with about 10-20% being excreted in the urine, mainly as glucuronide conjugates
Lager
Store at RT
Einzelnachweise
1) Forsberg?et al.?(2003),?Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat; J. Pharmacol. Exp. Ther.,?304?498 2) Merello?et al. (1994),?Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson’s disease; J. Neurol. Neurosurg. Psychiatry,?57?186 3) Giovanni?et al. (2010),?Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta amyloid and protect against amyloid-induced toxicity; J. Biol. Chem.,?285?14941 4) Chen?et al. (2016),?Entacapone is an Antioxident More Potent than Vitamin C and Vitamin E for Scavenging of Hypochlorous Acid and Peroxynitrite, and the Inhibition of Oxidative Stress-induced Cell Death; Med. Sci. Monit.,?22?687

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