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Ethacrynic acid

Product Name
Ethacrynic acid
CAS No.
58-54-8
Chemical Name
Ethacrynic acid
Synonyms
ETACRYNIC ACID;edecrin;mingit;mk-595;reomax;uregit;edecril;otacril;endecril;edecrina
CBNumber
CB8215310
Molecular Formula
C13H12Cl2O4
Formula Weight
303.14
MOL File
58-54-8.mol
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Ethacrynic acid Property

Melting point:
125 °C
Boiling point:
480.0±45.0 °C(Predicted)
Density 
1.3562 (estimate)
storage temp. 
2-8°C
solubility 
DMSO: soluble20mg/mL, clear
pka
3.50(at 25℃)
form 
powder
color 
white to beige
Water Solubility 
Soluble in ethanol, chloroform, ether, ammonia, carbonates, and methanol. Insoluble in water.
Merck 
3717
CAS DataBase Reference
58-54-8(CAS DataBase Reference)
EPA Substance Registry System
Ethacrynic acid (58-54-8)
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Safety

Hazard Codes 
Xn
Risk Statements 
20/21/22-36/37/38
Safety Statements 
26-36
WGK Germany 
3
RTECS 
AG6600000
HS Code 
2918992090
Hazardous Substances Data
58-54-8(Hazardous Substances Data)
Toxicity
LD50 in mice (mg/kg): 176 i.v.; 627 orally (Peck)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML1083
Product name
Ethacrynic acid
Purity
≥97% (HPLC)
Packaging
10mg
Price
$26.1
Updated
2024/03/01
Sigma-Aldrich
Product number
1256004
Product name
Ethacrynic acid
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
200mg
Price
$436
Updated
2024/03/01
Alfa Aesar
Product number
J63684
Product name
Ethacrynic acid
Packaging
1g
Price
$85.7
Updated
2024/03/01
Cayman Chemical
Product number
19536
Product name
Ethacrynic Acid
Purity
≥98%
Packaging
1g
Price
$69
Updated
2024/03/01
Cayman Chemical
Product number
19536
Product name
Ethacrynic Acid
Purity
≥98%
Packaging
5g
Price
$325
Updated
2024/03/01
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Ethacrynic acid Chemical Properties,Usage,Production

Description

Ethacrynic acid is a loop diuretic with anticancer activity., It inhibits the Na-K-2Cl (NKCC) cotransporter in duck erythrocytes (IC50 = 0.18 mM) and ATP-dependent chloride uptake in rat renal plasma membrane vesicles when used at a concentration of 0.3 mM., Ethacrynic acid also inhibits glutathione S-transferase P1-1 (GSTP1-1) and GSTA3-3 (IC50s = 4.9 and ~0.4 μM, respectively), and inhibits Wnt/β-catenin signaling in a cell-based reporter assay. It is cytotoxic to primary chronic lymphocytic leukemia cells (IC50 = 8.56 μM), as well as MCF-7, MDA-MB-231, and 4T1 cancer cells (IC50s = 45.53, 39.64, and 25.23 μM, respectively). Ethacrynic acid (250 μg per day) increases tumor growth reduction induced by the EGFR family inhibitors afatinib (Item Nos. 11492 | 21567) or neratinib in a 4T1 murine breast cancer model. Formulations containing ethacrynic acid have been used in the treatment of edema.

Chemical Properties

White Solid

Originator

Hydromedin,MSD,W. Germany,1966

Uses

Ethacrynic acid is a powerful diuretic prescribed for edema associated with cardiac insufficiency, renal edema that does not respond to other diuretics, and edema of the brain and lungs.

Uses

Ethacrynic acid is used to inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.

Uses

A diuretic used to treat high blood pressure and swelling caused by congestive heart failure, liver failure and kidney failure.

Definition

ChEBI: An aromatic ether that is phenoxyacetic acid in which the phenyl ring is substituted by chlorines at positions 2 and 3, and by a 2-methylidenebutanoyl group at position 4. It is a loop diuretic used to treat high blood pressure resulting from diseases such as congestive heart failure, liver failure, and kidney failure. It is also a glutathione S-transferase (EC 2.5.1.18) inhibitor.

Manufacturing Process

Step A: Preparation of 2,3-Dichloro-4-Butyrylphenoxy Acid - The product is prepared using the following ingredients: 22.1 grams (0.1 mol) 2,3- dichlorophenoxyacetic acid; 21.3 grams (0.2 mol) n-butyryl chloride; and 53.3 grams (0.4 mol) powdered aluminum chloride.
The 2,3-dichlorophenoxyacetic acid and n-butyryl chloride are placed in the reaction vessel and stirred while the aluminum chloride is added portionwise over a 45-minute period. The mixture then is heated on the steam bath for 3 hours and allowed to cool to room temperature. The gummy product obtained is added to a mixture of 300 ml of crushed ice and 30 ml concentrated hydrochloric acid. The resulting mixture is extracted with ether and the extract evaporated at reduced pressure. The residue is suspended in boiling water and dissolved by addition of a minimum quantity of 40% sodium hydroxide. After treatment with decolorizing charcoal and filtering, the hot filtrate is made acid to Congo red paper and chilled in ice.
The oil that separates is extracted with ether, the extract dried over anhydrous sodium sulfate and then evaporated at reduced pressure. The residue is dissolved in boiling benzene (75 ml) treated with decolorizing charcoal, filtered, treated with boiling cyclohexane (275 milliliters) and cooled to give 22.3 grams of 2,3-dichloro-4-butyrylphenoxyacetic acid. After several recrystallizations from a mixture of benzene and cyclohexane, then from methyl cyclohexane, next from a mixture of acetic acid and water, and finally from methylcyclohexane, the product melts at 110° to 111°C (corr).
Step B: Preparation of 2,3-Dichloro-4-[2-(Dimethylaminomethyl) Butyryl]Phenoxyacetic Acid Hydrochloride - In a 100 ml round flask equipped with an outlet tube suitable for application of intermittent suction, an intimate mixture of 5.20 grams (0.0179 mol) 2,3-dichloro-4-butyrylphenoxyacetic acid; 0.63 gram (0.0209 mol) paraformaldehyde; 1.59 grams (0.0195 mol) dry dimethylamine hydrochloride; and 4 drops acetic acid is heated on the steam bath for about 1.5 hours during which period suction is applied for about 1 minute intervals five or six times. Upon cooling, a solid is obtained, The crude reaction product is triturated with ether to give 5.8 grams (85%) of 2.3- dichloro-4-[2-dimethylaminomethyl)butyryl]phenoxyacetic acid hydrochloride in the form of a white solid. After two recrystallizations from a mixture of methanol and ether, the product melts at 165° to 167°C.
Step C: Preparation of 2,3-Dichloro-4-(2-Methylenebutyryl) Phenoxyacetic Acid - The Mannich compound obtained as described above is treated with aqueous sodium bicarbonate to form 2,3-dichloro-4-(2- methylenebutyryl)phenoxyacetic acid, MP 115° to 118°C. Two recrystallizations from a mixture of benzene and cyclohexane give white solid material melting at 118.5° to 120.5°C.

brand name

Edecrin (Merck).

Therapeutic Function

Diuretic, Cardiotonic, Smooth muscle relaxant, Respiratory stimulant

General Description

White solid.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Ethacrynic acid may react vigorously with strong oxidizing agents. Can react exothermically with reducing agents (such as alkali metals and hydrides) to release gaseous hydrogen. May react exothermically with acids. Reacts exothermically with all bases both organic (for example, the amines) and inorganic.

Fire Hazard

Ethacrynic acid is probably combustible.

Biochem/physiol Actions

Ethacrynic acid is non sulfonamide loop diuretic that is used to treat high blood pressure and the swelling caused by diseases like congestive heart failure. Ethacrynic acid blocks sodium-potassium-chloride cotransport. Also, Ethacrynic acid potently inhibits glutathione S-transferase family members. Studies show that ethacrynic acid potently inhibits Tgase-2 (transglutaminase-2) dependent metastasis of cancer cells including lung and pancreatic cancers.

Mechanism of action

The mechanism of action of ethacrynic acid appears to be more complex than the simple addition of sulfhydryl groups of the enzyme to the drug molecule. When the double bond of ethacrynic acid is reduced, the resultant compound is still active, although the diuretic activity is diminished. The sulfhydryl groups of the enzyme would not be expected to add to the drug molecule in the absence of the α,β-unsaturated ketone.
These compounds are potent high-ceiling diuretics that resemble ethacrynic acid in their mechanism of action. The ethyl ester group represents a pro-drug that can be easily hydrolyzed to the free carboxyl group. As in ethacrynic acid, a 2,3-dichloro substitution is necessary. In addition, a para-hydroxyl group and an unsubstituted aminomethyl group on the benzene ring are highly beneficial. The carbonyl group can be replaced with an ether or sulfide group. These compounds have no ability to add the sulfhydryl groups of the kidney enzymes. The complete mechanism of action of these compounds remains in doubt.

Synthesis

Ethacrynic acid?a[2,3-dichloro-4-(2-methylenbutyryl)phenoxy]acetic acid (21.4.9), is synthesized from 2,3-dichlorophenoxyacetic acid. This is acylated with butyroyl chloride, forming 4-butyroyl-2,3-dichlorophenoxyacetic acid (21.4.7), which is further aminomethylated under Mannich reaction conditions using dimethylamine and formaldehyde. The resulting product (21.4.8) undergoes further thermal degredation, forming an unsaturated ketone?aethacrynic acid (21.4.9).

Veterinary Drugs and Treatments

Ethacrynic acid is a loop diuretic that shares the same indications as furosemide (congestive cardiomyopathy, pulmonary edema, hypercalcuric nephropathy, uremia, as adjunctive therapy in hyperkalemia and, occasionally, as an antihypertensive agent). Its use has been largely supplanted in the armamentarium by furosemide for these indications.
Ethacrynic acid may be useful in the treatment of nephrogenic diabetes insipidus as it may cause a paradoxical decrease in urine volume. Other uses include the adjunctive treatment of hypercalcemia and to increase the excretion of bromide in the treatment of bromide toxicity.

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Ethacrynic acid Suppliers

Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel
4006608290; 18621169109
Fax
86-21-61259102
Email
market03@meryer.com
Country
China
ProdList
40241
Advantage
62
WUHAN SUN-SHINE BIO-TECHNOLOGY Co., Ltd.
Tel
17702719238 17702719238
Email
sales@sun-shinechem.com
Country
China
ProdList
892
Advantage
64
Chemsky(shanghai)International Co.,Ltd.
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
32344
Advantage
50
Syntechem Co.,Ltd
Tel
Fax
E-Mail Inquiry
Email
info@syntechem.com
Country
China
ProdList
12990
Advantage
57
Sinopharm Chemical Reagent Co,Ltd.
Tel
86-21-63210123
Fax
86-21-63290778 86-21-63218885
Email
sj_scrc@sinopharm.com
Country
China
ProdList
9823
Advantage
79
Spectrum Chemical Manufacturing Corp.
Tel
021-021-021-67601398-809-809-809 15221380277
Fax
021-57711696
Email
marketing_china@spectrumchemical.com
Country
China
ProdList
9664
Advantage
60
Beijing HuaMeiHuLiBiological Chemical
Tel
010-56205725
Fax
010-65763397
Email
waley188@sohu.com
Country
China
ProdList
12338
Advantage
58
UHN Shanghai Research & Development Co., Ltd.
Tel
021-58958002 18930822973
Fax
+86 (21) 5895-8628
Email
SALES@UHNSHANGHAI.COM
Country
China
ProdList
977
Advantage
58
Shanghai Aladdin Bio-Chem Technology Co.,LTD
Tel
400-6206333 18521732826;
Fax
021-50323701
Email
market@aladdin-e.com
Country
China
ProdList
24835
Advantage
65
TargetMol Chemicals Inc.
Tel
021-33632979 15002134094
Fax
021-33632979
Email
marketing@targetmol.com
Country
China
ProdList
7934
Advantage
58
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View Lastest Price from Ethacrynic acid manufacturers

Baoji Guokang Healthchem co.,ltd
Product
Ethacrynic acid 58-54-8
Price
US $127.00/g
Min. Order
2g
Purity
99%
Supply Ability
50kg
Release date
2021-06-03
Career Henan Chemical Co
Product
Ethacrynic acid 58-54-8
Price
US $1.00/KG
Min. Order
1KG
Purity
98%-99.9%HPLC
Supply Ability
100KG
Release date
2020-02-04

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