Epalrestat Chemical Properties

Melting point:

210-217 C

Boiling point:

516.8±60.0 °C(Predicted)

Density 

1.43±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMSO: soluble5mg/mL, clear (warmed)

pka

3.62±0.10(Predicted)

form 

powder

color 

yellow to orange

Merck 

14,3605

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.

InChI

InChI=1S/C15H13NO3S2/c1-10(7-11-5-3-2-4-6-11)8-12-14(19)16(9-13(17)18)15(20)21-12/h2-8H,9H2,1H3,(H,17,18)/b10-7+,12-8-

InChIKey

CHNUOJQWGUIOLD-NFZZJPOKSA-N

SMILES

S1/C(=C\C(\C)=C\C2=CC=CC=C2)/C(=O)N(CC(O)=O)C1=S

Safety Information

RIDADR 

2811

WGK Germany 

3

RTECS 

XJ5131855

HS Code 

2932.99.7000

HazardClass 

6.1

PackingGroup 

II

MSDS

• Language:English Provider:Epalrestat

Epalrestat Usage And Synthesis

Description

Epalrestat is the second aldose reductase inhibitor to be introduced worldwide and the first to be launched in Japan. The compound is indicated for the treatment of diabetic neuropathy. It is also being investigated for diabetic retinopathy and nephropathy.

Chemical Properties

Red Solid

Originator

Ono (Japan)

Uses

Epalrestat has been used as an aldose reductase inhibitor:

• in the dahomey larvae diet fed forDrosophila
• for non-irradiated and X-ray irradiated human aldose reductase
• to test its protective effect in mice with bleomycin-induced pulmonary fibrosis

Uses

Epalrestat is an aldose reductase inhibitor with IC50 of 72 nM

Uses

An aldose reductase inhibitor. It is used in treatment of diabetic neuropathy.

Definition

ChEBI: A monocarboxylic acid that is 1,3-thiazolidine which is substituted on the nitrogen by a carboxymethyl group, at positions 2 and 4 by thioxo and oxo groups, respectively, and at position 5 by a 2-methyl-3-phenylprop-2-en-1-ylidene group. It is an inhibitor of aldose reductase (which catalyses the conversion of glucose to sorbitol) and is used for the treatment of some diabetic complications, including neuropathy.

brand name

Kinedak

Biochem/physiol Actions

Epalrestat inhibits Aldose Reductase (AR) involved in the rate limiting step in the conversion of glucose to sorbitol under hyperglycemic conditions. Aldose reductase has been the target of multiple clinical investigatons to treat diabetic neuropathy and retinopathy. Epalrestat is an approved drug in Japan and India, used for the treatment of diabetic neuropathy.

Synthesis

General procedure for the synthesis of the compound (CAS:82158-86-9) from 3-carboxymethyl bypassed tannin and trans-α-methyl cinnamaldehyde: Rhodanine-3-acetic acid (131.0 g) was dissolved in 700 mL of N,N-dimethylformamide (DMF), followed by a slow addition to the reaction mixture at 25-35°C of (E)-2-methyl-3-phenyl Acrolein (100.0 g) and 200 mL of DMF. next, a solution of ammonium acetate (63.27 g) dissolved in 60 mL of water was added to the reaction system, maintained at a temperature of 30-35°C and stirred for 4 hours. Upon completion of the reaction, the reaction mixture was cooled to 10-15°C. At this temperature, concentrated hydrochloric acid (100.0 g) was slowly added and the reaction temperature was maintained at 10-15°C for 2 hours. At the end of the reaction, the reaction mixture was filtered and the solid product was washed with DMF. Finally, the product was dried by rotary evaporation for 2-4 hours to give 2-((Z)-5-((E)-2-methyl-3-phenylpropenyl)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid in the yield of 260.50 g. The reaction was carried out at a temperature of 10-15°C for 2 hours.

References

[1] R KIKKAWA. Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats.[J]. Diabetologia, 1983, 24 4: 290-292. DOI:10.1007/bf00282716
[2] H TERASHIMA. Effects of a new aldose reductase inhibitor on various tissues in vitro.[J]. Journal of Pharmacology and Experimental Therapeutics, 1984, 229 1: 226-230.
[3] MARY ANN RAMIREZ  Nancy L B. Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy.[J]. Pharmacotherapy, 2008, 28 5: 646-655. DOI:10.1592/phco.28.5.646

Epalrestat(82159-09-9)Related Product Information

• 2,2'-Dithiobis(benzothiazole)
• Triphenyltin acetate
• PHENYL VALERATE
• Fosthiazate
• Acetonitrile
• Methylparaben
• Methyl acrylate
• Methyl acetate
• Kresoxim-methyl
• Methylchloroisothiazolinone/methylisothiazolinone mixture (MCIT/MIT)
• Paraquat dichloride
• Basic Violet 1
• Benzothiazole
• Methanol
• 1-Phenyl-2-nitropropene
• 4-oxo-2-mercapto-thiazole-3-acetic acid (intermediate of epalrestat)
• Brexpiprazole
• 4-oxo-5-[(2E)-3-phenyl-2-propen-1-ylidene]-2-thioxo-, (5Z)-