82159-09-9 Usage
Description
Epalrestat is a monocarboxylic acid that is 1,3-thiazolidine, 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 a potent inhibitor of aldose reductase, an enzyme that catalyzes the conversion of glucose to sorbitol, and is used for the treatment of diabetic complications, including neuropathy. Epalrestat is the second aldose reductase inhibitor to be introduced worldwide and the first to be launched in Japan. It is indicated for the treatment of diabetic neuropathy and is also being investigated for diabetic retinopathy and nephropathy. Epalrestat is a red solid and is marketed under the brand name Kinedak.
Uses
Used in Pharmaceutical Industry:
Epalrestat is used as an aldose reductase inhibitor for the treatment of diabetic neuropathy. It helps in managing the symptoms and complications associated with diabetic neuropathy by inhibiting the enzyme aldose reductase, which is responsible for the conversion of glucose to sorbitol.
Used in Research Applications:
Epalrestat has been used in various research studies to investigate its protective effects in different conditions. For instance, it has been used in the dahomey larvae diet fed for Drosophila to study its effects on non-irradiated and X-ray irradiated human aldose reductase. Additionally, it has been used to test its protective effect in mice with bleomycin-induced pulmonary fibrosis, a condition characterized by scarring and thickening of lung tissue.
Used in Drug Development:
Epalrestat is used as a reference compound in the development of new drugs targeting aldose reductase inhibition. Its IC50 value of 72 nM makes it a potent inhibitor, which can be used to compare the effectiveness of newly synthesized compounds or drug candidates.
Originator
Ono (Japan)
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
Check Digit Verification of cas no
The CAS Registry Mumber 82159-09-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,1,5 and 9 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 82159-09:
(7*8)+(6*2)+(5*1)+(4*5)+(3*9)+(2*0)+(1*9)=129
129 % 10 = 9
So 82159-09-9 is a valid CAS Registry Number.
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+
82159-09-9Relevant articles and documents
Preparation method of epalrestat
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Paragraph 0047-0070, (2021/10/11)
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
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Paragraph 0058, (2017/08/08)
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