Diflunisal

Bezeichnung:Diflunisal

CAS-Nr22494-42-4

Englisch Name:Diflunisal

CBNumberCB9674965

SummenformelC13H8F2O3

Molgewicht250.2

MOL-Datei22494-42-4.mol

Synonyma

Diflunisal

Diflunisal physikalisch-chemischer Eigenschaften

Schmelzpunkt	207-209?C
Siedepunkt	386.9±42.0 °C(Predicted)
Dichte	1.3505 (estimate)
storage temp.	Keep in dark place,Sealed in dry,Room Temperature
Löslichkeit	Practically insoluble in water, soluble in ethanol (96 per cent). It dissolves in dilute solutions of alkali hydroxides.
Aggregatzustand	Solid
pka	pKa 3.3 (H2O I=0.1) (Uncertain)
Farbe	White
Wasserlöslichkeit	6.186mg/L(24.99 ºC)
CAS Datenbank	22494-42-4(CAS DataBase Reference)
NIST chemische Informationen	Diflunisal(22494-42-4)

Sicherheit

Kennzeichnung gefährlicher	Xn,Xi
R-Sätze:	22-36/37/38-63
S-Sätze:	22-26-36
WGK Germany	3
RTECS-Nr.	DV2030000
Hazard Note	Irritant
HS Code	2918290000
Toxizität	LD50 orally in female mice: 439 mg/kg (Stone)

Gefahreninformationscode (GHS)

Diflunisal Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R63:Kann das Kind im Mutterleib möglicherweise schädigen.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Diflunisal is more potent than aspirin but produces fewer side effects and has a biological half-life three to four times greater than that of aspirin. It is rapidly and completely absorbed on oral administration, with peak plasma levels being achieved within 2 to 3 hours of administration. It is highly bound (99%) to plasma proteins after absorption. Its elimination half-life is 8 to 12 hours, and it is excreted into urine primarily as glucuronide conjugates. The most frequently reported side effects include disturbances of the GI system (e.g., nausea, dyspepsia, and diarrhea), dermatological reactions, and CNS effects (e.g., dizziness and headache).
Beschreibung
Diflunisal is a non-steroidal anti-inflammatory drug (NSAID) that inhibits both COX-1 (IC₅₀ = 113 μM) and COX-2 (IC₅₀s = 8.2 and 134 μM for human whole blood assay and human-modified whole blood assays, respectively). Peak plasma levels are achieved within two hours, with little metabolism before excretion in the urine. The terminal plasma half-life is approximately eight hours.
Chemische Eigenschaften
White Solid
Originator
Dolobid,Morson,UK,1978
Verwenden
As a prostaglandin synthetase inhibitor, diflunisal exhibits analgesic, fever-reducing, and anti-inflammatory action. It is used for long- and short-lasting symptomatic relief of low to moderate pain in osteoarthritis and rheumatoid arthritis.
Verwenden
Salicylate; non-selective cyclo-oxygenase inhibitor; antipyretic; analgesic; anti- inflammatory.
Verwenden
Diflunisal acts as an analgesic agent, used in Alzheimer’s studies (1,2,3) as an anti-inflammatory. As well as in autolytic regulation of human kallikrein -related peptidase 6 (4).
Definition
ChEBI: Diflunisal is an organofluorine compound comprising salicylic acid having a 2,4-difluorophenyl group at the 5-position. It has a role as a non-steroidal anti-inflammatory drug and a non-narcotic analgesic. It is an organofluorine compound and a monohydroxybenzoic acid. It is functionally related to a salicylic acid and a 1,3-difluorobenzene.
Manufacturing Process
A mixture of 10 g of 4-(2',4'-difluorophenyl)-phenol and 27.2 g of potassium carbonate is exposed to carbon dioxide at 1,300 psi and 175°C. The dark mass obtained from this carbonation is then dissolved in 300 ml of water and 200 ml of methylene chloride and the two layers separated. The water layer is then extracted with 100 ml of methylene chloride and then acidified with 2.5 N hydrochloric acid. This mixture is then filtered and the cake dried in vacuo to yield 5.32 g of the crude product. The crude product is then recrystallized from benzene-methanol. An additional crystallization of this semipure material from benzene-methanol yields analytically pure 2-hydroxy-5-(2',4'- difluorophenyl)-benzoic acid (MP 210-211°C).
Trademarks
Biartac (Merck Sharp & Dohme, Belgium), Diflonid (Dumex, Denmark, Sweden), Diflusal (Merck Sharp & Dohme, Belgium), Dolobid (Frosst, Canada; Logos, South Africa; Merck, USA; Morson, UK), Dolobis (M.S.D.-Chibret, France), Fluniget (Merck Sharp & Dohme, Austria).
Therapeutic Function
Analgesic, Antiinflammatory
Allgemeine Beschreibung
Diflunisal is a salicylate with greater anti-inflammatory and analgesic potency and with a long plasma half-life that allows for twice-a-day dosage. Without an O-acetyl group it is a reversible inhibitor of cyclooxygenase. It is comparable in efficacy to aspirin in the treatment of osteoarthritis and rheumatoid arthritis but is much better tolerated.
Allgemeine Beschreibung
Diflunisal (Dolobid), is a longer acting and more potent drugthan aspirin because of its hydrophobic, 2,4-difluorophenylgroup attached to the 5-position of the salicyclic acid. In alarge-scale comparative study with aspirin, it was also bettertolerated with less GI complications than aspirin. It ismarketed in tablet form for treating mild to moderate postoperativepain as well as RA and OA.
Diflunisal is highly protein bound. Its metabolism is subjectto a dose-dependent, saturable, and capacity-limitedglucuronide formation. This unusual pharmacokineticprofile is a result of an enterohepatic circulation and the reabsorptionof 65% of the drug and its glucuronides, followedby cleavage of its unstable, acyl glucuronide back tothe active drug. Thus, diflunisal usage in patients with renalimpairment should be closely monitored.
Mechanism of action
Diflunisal is a weak inhibitor of both COX-1 and COX-2.
Pharmakologie
Peak plasma concentrations are reached within 2 to 3 h after oral dosing. Diflunisal is strongly bound to plasma protein (> 99 %), has a long elimination half-life (8–12 h) and nonlinear elimination kinetics. Hence, it is used with an initial loading dose (1000 mg) and a lower maintenance dose (500–1000 mg/d).
Pharmakokinetik
Diflunisal is more potent than aspirin but produces fewer side effects and has a biological half-life three to four times greater than that of aspirin. It is rapidly and completely absorbed on oral administration, with peak plasma levels being achieved within 2 to 3 hours of administration. It is highly bound (99%) to plasma proteins after absorption. Its elimination half-life is 8 to 12 hours, and it is excreted into urine primarily as glucuronide conjugates. The most frequently reported side effects include disturbances of the GI system (e.g., nausea, dyspepsia, and diarrhea), dermatological reactions, and CNS effects (e.g., dizziness and headache).
Clinical Use
Diflunisal (pKa 3.3) was introduced in the United States in 1982 and has gained considerable acceptance as an analgetic and as a treatment of rheumatoid arthritis and osteoarthritis. Diflunisal is metabolized primarily to ether and ester glucuronide conjugates.
Nebenwirkungen
The main side effects are gastrointestinal disturbances, headache and rash.
Sicherheitsprofil
Poison by ingestion, subcutaneous, and intraperitoneal routes. Human systemic effects by ingestion: tolerance, and cholestatic jaundce (due to the stoppage of the flow of bile), agranulocytosis, increased body temperature. An experimental teratogen. Other experimental reproductive effects. An analgesic and anti-inflammatory agent. When heated to decomposition it emits toxic fumes of F-. See also FLUORIDES.
Synthese
Diflunisal, 2??,4??-difluoro-4-hydroxy-3-byphenylcarboxylic acid (3.2.5), is synthesized from a diazonium salt, which is synthesized from 2,4-difluoroaniline and isoamyl nitrite, and anisole in the presence of copper (I) salts by the classic scheme of making diaryls. The resulting 4-(2,4-difluorophenyl)anisole (3.2.3) is demethylated by hydrogen iodide into 4-(2,4-difluorophenyl)-phenol (3.2.4). This product is reacted with carbon dioxide in the presence of a base according to the Kolbe¨CSchmitt phenol carboxylation method, giving diflunisal (3.2.5) [64¨C67].

Diflunisal Upstream-Materialien And Downstream Produkte

Diflunisal Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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