3562-84-3 Usage
Description
Benzbromarone,a non-competitive inhibitor of xanthine oxidase,is apotent uricosuric drug used in the treatment of gout.Benzbromarone is a benzofuran derivative chemically related to amiodarone. It increases uric acid excretion by non-specificallyinhibiting its tubular reabsorption.lt is used in patients with venous disorders to prevent,retard,or reverse varicose degenerative changes in the vessel wall.Benzbromarone causes diarrhea (3-4% of patients), urate and oxalate stones,urinary sand,renal colic,and allergy in a small number of patients.Liver damage, which reverses after withdrawal, has been described (SEDA-18,108).
Chemical Properties
Pale Beige Solid
Originator
Desuric,Labaz,Switz.
Uses
Different sources of media describe the Uses of 3562-84-3 differently. You can refer to the following data:
1. Benzbromarone is a benzofuran derivative that has been reported to lower serum urate levels in animals and human studies. In normal and hyperuricaemic subjects, benzbromarone reduced serum uric acid levels by one-third to one-half. In comparison with other urate-lowering drugs, 80 mg of micronized or 100 mg of nonmicronized benzbromarone had equal urate-lowering activity to 1–1.5 g of probenecid or 400–800 mg of sulfinpyrazone. The mechanism of the urate-lowering activity of benzbromarone appears to be attributable to its uricosuric activity. In rats, benzobromarone inhibited urate reabsorption in the proximal tubules when given at 10 mg/kg i.v. In isolated rat liver preparation, benzbromarone inhibits xanthine oxidase in vitro but not in vivo . In humans, this compound only weakly inhibits xanthine oxidase and no increase in urinary excretion of xanthine or hypoxanthine was observed. After oral administration, about 50% of benzbromarone is absorbed. The drug undergoes extensive dehalogenation in the liver and is excreted mainly in the bile and feces. For control of gout the usual therapeutic dose is 100–200 mg daily. Benzbromarone has few side effects and is usually well tolerated.
2. Benzbromarone is a uricosuric agent used in the treatment of gout and hyperuricemia. Studies show that use of Benzbromarone results in less complications than other uricosuric agent such as Allopurinol.
3. Coronarodilatator;Uric acid transport inhibitor
Definition
ChEBI: Benzbromarone is 1-Benzofuran substituted at C-2 and C-3 by an ethyl group and a 3,5-dibromo-4-hydroxybenzoyl group respectively. An inhibitor of CYP2C9, it is used as an anti-gout medication. It has a role as a uricosuric drug. It is a member of 1-benzofurans and an aromatic ketone. It derives from a 2,6-dibromophenol.
Manufacturing Process
The propyl analog of the benzbromarone intermediate containing an ethyl
group is prepared as follows: to a solution of potassium hydroxide (56 g = 1
mol) in absolute ethyl alcohol (750 cc) is added one mol of salicylic aldehyde
(122 grams). The mixture is brought to boiling point in a water-bath until the
potassium salt formed is dissolved. One mol of ethyl chloromethyl ketone
(106.5 grams) (methyl chloromethyl ketone or chloracetone in the case of
benzbromarone) is gradually added and the solution boiled in a reflux
condenser for two hours.
After cooling, the potassium chloride precipitate is separated off by filtration,
and the greater part of the solvent removed by distillation. The residue is then
puritied by distillation. In this way, 140 grams of 2-propionyl coumarone are
obtained, boiling at 135°C under 15 mm Hg. A mixture is then prepared as
follows: 215 grams of 2-propionyl coumarone, 550 cc of diethylene glycol and
200 grams of hydrazine hydrate at 85% and maintained at boiling point in a
reflux condenser for 10 minutes. After cooling, 180 grams of potassium
hydroxide are added and the mixture brought up to 120°-130°C. This
temperature is maintained until no more nitrogen is liberated (about 1 hour).
The mixture is then distilled by means of super-heated steam (150°-160°C).
The distillate is neutralized by means of concentrated HCl, decanted, and the
aqueous layer extracted by means of ether. The oily layer and the ethereal
extract are mixed, washed with diluted HCl, then with water, and finally dried
over sodium sulfate. The solvent is removed and the residue rectified under reduced pressure. In this way, 130 grams of 2-propyl coumarone are
obtained, boiling at 112°C under 17 mm of mercury.
The following substances are then placed in a 250 cc flask fitted with a stirrer
and a separatory funnel: 12.96 grams of 2-propyl coumarone, 55 cc of carbon
sulfide and 14 grams of anisoyl chloride. The mixture is cooled by means of
iced water and 21.5 grams of stannic chloride introduced dropwise, while the
mixture is stirred. Stirring is continued for three hours at 0°C, after which the
mixture is allowed to stand overnight. 50 cc of carbon sulfide is added and the
mixture is treated, while being stirred, with the following: 20 cc of HCl and
100 cc of iced water. The organic layer is decanted and washed with water,
dried over silica gel and rectified.
16.16 grams of 2-propyl-3-anisoyl coumarone are obtained (Yield: 72%),
boiling at 189°C under 0.5 mm Hg. The methoxylated coumarone so obtained
is mixed as follows: 1 part of 2-propyl-3-anisoylcoumarone and 2 parts of
pyridine hydrochloride and the mixture maintained for one hour under a
stream of dry nitrogen in an oil bath at 210°C (under a vertical condenser).
After cooling, the mixture is triturated with 0.5 N hydrochloric acid (10 parts).
The aqueous layer is separated and the residue extracted with ether. The
ethereal extract is treated with 20 parts of 1% caustic soda. The alkaline layer
is separated by decanting and acidified by means of diluted HCl. The
precipitate is purified by recrystallization in aqueous acetic acid.
0.8 part of 2-propyl-3p-hydroxybenzoyl coumarone is obtained, melting at
123°C. Then the dibromo counterpart of benzbromarone may be prepared as
follows: 8.05 g of 3-ethyl-2-p-hydroxybenzoyl coumarone, prepared as
described above, are dissolved in very silght excess of 3% caustic soda. To
this solution is gradually added a slight excess of bromine dissolved in a 25%
aqueous solution of potassium bromide. The resultant solution is acidified with
a 20% solution of sodium bisulfite, centrifuged, washed with water and then
dried under vacuum. The product is then recrystallized in acetic acid and 13.6
g of 2-(4'-hydroxy-3',5'-dibromo-benzoyl)-3-ethyl coumarone obtained. MP
151°C.
Therapeutic Function
Uricosuric, Antiarthritic
Safety Profile
Poison by ingestion,
intravenous, and intraperitoneal routes.
Moderately toxic by subcutaneous route.
Experimental teratogenic and reproductive
effects. A uricosuric agent which promotesthe excretion of uric acid in the urine. A
flammable liquid. When heated to
decomposition it emits toxic fumes of Br-.
See also KETONES.
Check Digit Verification of cas no
The CAS Registry Mumber 3562-84-3 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 3,5,6 and 2 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 3562-84:
(6*3)+(5*5)+(4*6)+(3*2)+(2*8)+(1*4)=93
93 % 10 = 3
So 3562-84-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H12Br2O3/c1-2-13-15(10-5-3-4-6-14(10)22-13)16(20)9-7-11(18)17(21)12(19)8-9/h3-8,21H,2H2,1H3
3562-84-3Relevant articles and documents
Preparation method of benzbromarone
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Paragraph 0023; 0028-0029; 0032; 0037-0038; 0041; 0046-0047, (2021/03/11)
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of benzbromarone. According to the method disclosed by the invention, polystyrene-loaded aluminum trichloride is used as a catalyst to carry out Friedel-Crafts acylation reaction, so that the catalytic effect is good, and the catalyst can be recycled, in the demethylation reaction process, aluminum trichloride is adopted to replace common pyridine hydrochloride, so that the reaction temperature can be reduced, and the yield can be increased, in the bromination reaction, sodium sulfide and hydrogen peroxide are adopted to replace bromine, so that the technical problems of strong corrosivity of bromine, great harm to human bodies and environmental pollution are solved, and meanwhile, the yield can be further improved.
DEVELOPING POTENT URATE TRANSPORTER INHIBITORS: COMPOUNDS DESIGNED FOR THEIR URICOSURIC ACTION
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Page/Page column 15, (2012/04/23)
A compound represented by the general Formula (I): a pharmaceutically acceptable salt or ester thereof, a solvate thereof, a chelate thereof, a non-covalent complex thereof, a pro-drug thereof, a deuterated radio-labeled analog thereof, and mixtures of any of the foregoing, wherein: A - K are individually selected from carbon or nitrogen; X = -O, -NR1,or -S; R1-11 are individually selected from the group consisting of-H, C1-C6 alkyl, C6-C aryl, substituted C6-C14 aryl, C1-C14-alkoxy, halogen, hydroxyl, carboxy, cyano, C1-C6-alkanoyloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, trifluoromethyl, hydroxy, C2-C6-alkoxycarbonyl, C2-C6-alkanoylamino, -O-R12, S-R12,-SO2-Ri2, -NHSO2R12 and -NHCO2R12, wherein R12 is phenyl, naphthyl, or phenyl or naphthly substituted with one to three groups selected from C1-C6-alkyl, C6-C10 aryl,C1-C6-alkoxy and halogen, and C4-C20 hydroxyheteroaryl wherein the heteroatoms are selected from the group consisting of sulfur, nitrogen, and oxygen.
Process for the preparation of 3-benzoyl benzofuran derivatives
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, (2008/06/13)
The invention relates to a process for the preparation of 3-benzoyl benzofuran derivatives of general formula: STR1 wherein a benzofuran derivative of general formula: STR2 is reacted in situ in the presence of aluminium chloride successively with phosgene or oxalyl chloride, and then with a phenolic derivative of general formula: STR3 to produce a complex which is hydrolysed to form the desired compound of 3-benzoyl benzofuran.