Tolcapone

Bezeichnung:Tolcapone

CAS-Nr134308-13-7

Englisch Name:Tolcapone

CBNumberCB9302569

SummenformelC14H11NO5

Molgewicht273.24

MOL-Datei134308-13-7.mol

Tolcapone physikalisch-chemischer Eigenschaften

Schmelzpunkt	126-1280C
Siedepunkt	485.6±45.0 °C(Predicted)
Dichte	1.419±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: ≥15mg/mL
pka	4.78±0.38(Predicted)
Aggregatzustand	powder
Farbe	yellow
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 2 months.
CAS Datenbank	134308-13-7(CAS DataBase Reference)

Sicherheit

Kennzeichnung gefährlicher	N
R-Sätze:	50
S-Sätze:	61
RIDADR	UN 3077 9 / PGIII
RTECS-Nr.	PC4952500
HS Code	2914710000
Toxizität	mouse,LD50,oral,1600mg/kg (1600mg/kg),BEHAVIORAL: ATAXIABEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION,Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 24(Suppl,

Gefahreninformationscode (GHS)

Tolcapone Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
Yellow Solid
Originator
Tasmar,Roche
Verwenden
Orally active inhibitor of central and peripheral catechol-O-methyltransferase (COMT). Antiparkinsonian
Verwenden
Tolcapone may be used in COMT-mediated cell signaling studies.
Tolcapone has been used in methyltransferase assay in human embryonic kidney 293 cells.
synthetische
preparation by demethylation of 4-hydroxy-3-methoxy-4′-methyl-5-nitrobenzophenone with hydrobromic acid in refluxing aque-ous acetic acid.
Definition
ChEBI: Tolcapone is benzophenone substituted on one of the phenyl rings at C-3 and C-4 by hydroxy groups and at C-5 by a nitro group, and on the other phenyl ring by a methyl group at C-4. It is an inhibitor of catechol O-methyltransferase. It has a role as an EC 2.1.1.6 (catechol O-methyltransferase) inhibitor and an antiparkinson drug. It is a member of benzophenones, a member of 2-nitrophenols and a member of catechols.
Manufacturing Process
Condensation of 4-benzyloxy-3-methoxybenzaldehyde with 4-lithium-toluene (prepared from 4-bromotoluene and butyl lithium) leads to the corresponding benzhydrole. Oxidation of the new formed hydroxyl in benzhydrole gives the 4-benzyloxy-3-methoxyphenyl)-p-tolylmethanone. Treatment of this compound with hydrogen bromide selectively removes the benzyl ether that is additionally activated by the transannular carbonyl group. The intermediate is then nitrated under standart conditions to give the (4-hydroxy-3-methoxy-5- nitrophenyl)-p-tolylmethanone. A second treatment of the last compound with hydrogen bromide cleaves the ether group, which is now activated by the adjacent nitro group. This last step affords the (3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone.
Therapeutic Function
Antiparkinsonian
Allgemeine Beschreibung
Tolcapone, 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone (Tasmar), is a yellow, odorless, nonhygroscopic,crystalline compound (pK_a＝4.78). Tolcapone israpidly absorbed after oral administration. Tolcapone ishighly bound to plasma albumin (＞98%), and its distributionis therefore restricted. Tolcapone has low first-pass metabolism.It is almost completely metabolized in the liver before excretion, and 60% is excreted by the kidney. The majormetabolite of tolcapone is an inactive glucuronide conjugate.COMT inhibitors increase chronotropic and arrhythmogeniceffects of epinephrine.Tolcapone is indicated as an adjunctto levodopa/carbidopa for the management of signs andsymptoms of PD.
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.
Clinical Use
Catechol-o-methyltransferase inhibitor:
Treatment of Parkinson’s disease
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antidepressants: avoid with MAOIs.
Stoffwechsel
Extensively metabolised, mainly by conjugation to the inactive glucuronide, but methylation by catecholO-methyltransferase to 3-O-methyltolcapone and metabolism by cytochrome P450 isoenzymes CYP3A4 and CYP2A6 also occurs. Approximately 60
% of a dose is excreted in the urine with the remainder appearing in the faeces.
Lager
Store at +4°C
Einzelnachweise
1) Manisto?et al.?(1992),?Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat; Br, J. Pharmacol.,?105?569 2) 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 3) Sant’Anna?et al.?(2016),?Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity; Nat. Commun.,?7?10787 4) Forester and Lambert (2015),?The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice; Funct. Foods,?17?183

Tolcapone Upstream-Materialien And Downstream Produkte

Tolcapone Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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