Benzaron

Bezeichnung:Benzaron

CAS-Nr1477-19-6

Englisch Name:Benzarone

CBNumberCB6893840

SummenformelC17H14O3

Molgewicht266.29

MOL-Datei1477-19-6.mol

Synonyma

Benzaron

Benzaron physikalisch-chemischer Eigenschaften

Schmelzpunkt	124.3°
Siedepunkt	369.5°C (rough estimate)
Dichte	1.1601 (rough estimate)
Brechungsindex	1.5490 (estimate)
storage temp.	2-8°C
Löslichkeit	DMSO (Slightly), Methanol (Slightly)
pka	7.68±0.15(Predicted)
Farbe	Pale Yellow to Light Brown
EPA chemische Informationen	Methanone, (2-ethyl-3-benzofuranyl)(4-hydroxyphenyl)- (1477-19-6)

Sicherheit

HS Code	2932.19.1000
Toxizität	LD50 ipr-mus: 200 mg/kg AIPTAK 154,94,65

Gefahreninformationscode (GHS)

Benzarone Chemische Eigenschaften,Einsatz,Produktion Methoden

Chemische Eigenschaften
Pale Yellow Solid
Originator
Fragivix,Labaz
Verwenden
Benzarone is an EYA (Eyes Absents), multifunctional protein involved in organogenesis, inhibitor which makes it a potent anticancer agent. EYA’s are over expressed in ovarian and breast cancers. As well it is involved in the synthesis of Human Uric Acid Transporter 1 inhibitors which may be used to treat kidney diseases.
Definition
ChEBI: Benzarone is a member of 1-benzofurans.
Manufacturing Process
The process of preparation of the 2-ethyl-3-(4'-hydroxybenzoyl)benzofurane includes the next steps: 1. To 1 mol of potassium hydroxide in absolute ethanol is added 1 mole of salicylic aldehyde. The mixture is brought to boiling point in water bath until the potassium salt formed is dissolved. One mole of coloroacetone is gradually added and the solution boiled in a reflux condenser for 2 hours. On cooling the potassium chloride precipitate is separated off by filtration. The residue is distilled to give 2-acetyl-1-benzofurane, BP: 135°C/15 mm Hg.
2. It was reduced by hydrazine hydrate in an alkaline medium (by process of Hyuang-Minlon, J.A.C.S., 1946, 68, 2487) to give 2-ethyl-1-benzofurane BP: 211°-212°C.
3. 2-Ethyl-1-benzofurane is condensed with 2-metoxybenzoyl chloride in the presence of tin tetrachloride (according to the process described by Bisagni, J.C.S., 1955, 3694). Thus 2-ethyl-3-(4-methoxybenzoyl)-1-benzofyrane is obtained. BP: 226°C/15 mm Hg.
4. 1 part of 2-ethyl-3-(4-methoxybenzoyl)-1-benzofyrane is mixed with 2 parts of pyridine hydrochloride and heated at an oil bath at 210°C in N2 current for 1 hour. On cooling 10 parts of 0.5 N HCl are added. A water layer is mixed with 20 parts of 1% NaOH. The alkaline layer is separated, acidified with diluted HCl. The dropped precipitate (2-ethyl-3-(4'-hydroxybenzoyl) benzofurane) is recrystallized from acetic acid. MP: 124.3°C.
Trademarks
Benzarin;Fragivix (r) forte;Vasco.
Therapeutic Function
Antihemorrhagic
Weltgesundheitsorganisation (WHO)
Benzarone is given by mouth and applied topically for treatment of various vascular peripheral disorders.The decision to suspend the marketing authorization results from several reports of toxic hepatitis, including one fatal case from within Germany. The product remains registered in Italy and France.
Biologische Aktivität
Benzarone is an active metabolite of the urate anion transporter 1 (URAT1) inhibitor benzbromarone. It inhibits URAT1 in Xenopus oocytes expressing the human enzyme (IC50 = 2.8 μM). Benzarone also inhibits the tyrosine phosphatase activity of eyes absent homolog 3 (EYA3; IC50 = 17.5 μM), as well as reduces the proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 7.5 μM. It uncouples oxidative phosphorylation in isolated rat liver mitochondria and induces apoptosis and necrosis in isolated rat hepatocytes. Benzarone (25 μg/g) reduces tumor growth in an A-673 Ewing sarcoma mouse xenograft model.
Sicherheitsprofil
Poison by intraperitoneal route. An experimental teratogen. Other experimental reproductive effects. A flammable liquid. When heated to decomposition it emits acrid and irritating smoke and fumes. See also KETONES.
Einzelnachweise
[1] W. STüBER H. M. Determination of benzbromarone, bromobenzarone and benzarone in plasma by gas chromatography—mass spectrometry[J]. Journal of Chromatography B: Biomedical Sciences and Applications, 1981, 224 2: Pages 327-331. DOI:10.1016/S0378-4347(00)80171-1.
[2] PRISKA KAUFMANN. Mechanisms of benzarone and benzbromarone-induced hepatic toxicity?[J]. Hepatology, 2005, 41 4: 925-935. DOI:10.1002/hep.20634.
[3] RAM NARESH PANDEY. Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agents.[J]. PLoS ONE, 2013: e84582. DOI:10.1371/journal.pone.0084582.
[4] MICHAEL F. WEMPE*. Developing Potent Human Uric Acid Transporter 1 (hURAT1) Inhibitors[J]. Journal of Medicinal Chemistry, 2011, 54 8: 2701-2713. DOI:10.1021/jm1015022.

Benzarone Upstream-Materialien And Downstream Produkte

Benzaron Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

1477-19-6, Benzarone Verwandte Suche:

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