82159-09-9

Basic information

• Product Name: Epalrestat
• Synonyms: 3-thiazolidineaceticacid,5-(2-methyl-3-phenyl-2-propenylidene)-4-oxo-2-thioxo;5-((1z,2e)-2-methyl-3-phenylpropenylidene)-4-oxo-2-thioxo-3-thiazolidineacet;e)-(e;EPALRESTAT;(e,e)-2-[5-(2-methyl-3-phenyl-prop-2-enylidene)-4-oxo-2-sulfanylidene-thiazo lidin-3-yl]acetic acid;AKOS BBS-00007767;OTAVA-BB BB7211260020;EPALRESTAT(KINEDAK)
• CAS NO: 82159-09-9
• Molecular Formula: C₁₅H₁₃NO₃S₂
• Molecular Weight: 319.4
• EINECS: 1312995-182-4
• Product Categories: Treatment of diabetic neuropathy;API's;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Hormone Drugs;API
• Mol File: 82159-09-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: 210-217 C
• Boiling Point: 516.8 °C at 760 mmHg
• Flash Point: 266.4 °C
• Appearance: yellow to orange/
• Density: 1.43 g/cm³
• Vapor Pressure: 1.66E-11mmHg at 25°C
• Refractive Index: 1.705
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: soluble5mg/mL, clear (warmed)
• PKA: 3.62±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• Merck: 14,3605
• CAS DataBase Reference: Epalrestat(CAS DataBase Reference)
• NIST Chemistry Reference: Epalrestat(82159-09-9)
• EPA Substance Registry System: Epalrestat(82159-09-9)

Safety Data

• RIDADR: 2811
• WGK Germany: 3
• RTECS: XJ5131855
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 82159-09-9(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 82159-09-9 differently. You can refer to the following data:
1. Epalrestat has been used as an aldose reductase inhibitor: in the dahomey larvae diet fed forDrosophilafor non-irradiated and X-ray irradiated human aldose reductaseto test its protective effect in mice with bleomycin-induced pulmonary fibrosis
2. Epalrestat is an aldose reductase inhibitor with IC50 of 72 nM
3. 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.

References

1) Kikkawa?et al. (1983)?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; Diabetologica,?24?290 2) Terashima?et al. (1984)?Effects of a new aldose reductase inhibitor on various tissues in vitro; J. Pharmacol. Exp. Ther.,?229?226 3) Ramirez and Borja (2008)?Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy; Pharmacotherapy,?28?646

InChI:InChI=1/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+

Upstream product

• 5718-83-2 rhodanine 3-acetic acid 
• 15174-47-7 α-methyl-trans-cinnamaldehyde 
• 863988-85-6 epalrestate 
• 124782-64-5 {5-[(Z)-2-Methyl-3-phenyl-prop-2-en-(E)-ylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid 

Downstream Products

• 1206474-03-4 epalrestat 1-(2-hydroxyethyl)-pyrrolidine salt 
• 1206474-02-3 epalrestat sodium salt 
• 1206474-01-2 epalrestat potassium salt 
• 124782-63-4 5-[(1Z,2Z)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid 

Relevant articles and documents

Preparation method of epalrestat

The invention relates to the technical field of medicines, in particular to a preparation method of epalrestat. The preparation method provided by the invention comprises the steps of mixing 3-carboxymethyl rhodanine, alpha-methylcinnamyl aldehyde, a catalyst and water, and sequentially carrying out condensation reaction and acid neutralization to obtain an epalrestat crude product, wherein the catalyst comprises a basic catalyst and a phase transfer catalyst; and mixing the epalrestat crude product with an alcohol organic solvent, and recrystallizing to obtain the epalrestat. The preparation method adopts water as a reaction solvent, and is safe and environment-friendly; the existing three procedures such as crude product preparation, acidification dissociation and recrystallization are simplified into two procedures such as crude product preparation and recrystallization, and the two procedures such as crude product preparation and acidification dissociation are combined into one, so that the procedures are simplified; and an alcohol organic solvent is adopted for recrystallization, so that recycling is facilitated.

PROCESS FOR PREPARING EPALRESTAT

PROBLEM TO BE SOLVED: To provide processes for preparing and purifying 2-((Z)-5-((E)-2-methyl-3-phenyl-allylidene)-4-oxo-2-thioxo-thiazolidin-3-yl) acetic acid (epalrestat). SOLUTION: Provided are processes for preparing and purifying epalrestat represented by the following formula (I), comprising the steps of: reacting rhodanine-3-acetic acid with (E)-2-methyl-3-phenyl-acryl-aldehyde in the presence of an ammonium salt(s) of an organic acid such as citric acid and DMF-containing solvent(s); isolating the produced epalrestat DMF solvate and drying it; suspending said epalrestat DMF solvate in ethanol; and further isolating the generated epalrestat crystal and drying it. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT