155141-29-0

Basic information

• Product Name: Rosiglitazone maleate
• Synonyms: 5-((4-[2-(METHYL-2-PYRIDINYLAMINO)-ETHOXY]-PHENYL)-METHYLENE)-2,4-THIAZOLIDINEDIONE;5-{p-[2-(methyl-2-pyridylamino)ethoxy]benzyl}-2,4-thiazolidinedione maleate;ROSIGLITAZONE MALEATE;RosiglitazoneTartrate;Avandi;BRL-49653c;RSIGLITAZONEMALEATE;5-(4-(2-(Methyl(pyridin-2-yl)aMino)ethoxy)benzyl)thiazolidine-2,4-dione Maleate
• CAS NO: 155141-29-0
• Molecular Formula: C₄H₄O₄*C₁₈H₁₉N₃O₃S
• Molecular Weight: 473.5
• EINECS: 1312995-182-4
• Product Categories: Active Pharmaceutical Ingredients;Antidiabetic;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Rosiglitazone;Heterocycles;Sulfur & Selenium Compounds;Inhibitor;API
• Mol File: 155141-29-0.mol

Chemical Properties

• Melting Point: 235-240°C
• Boiling Point: 585 °C at 760 mmHg
• Flash Point: 307.6 °C
• Appearance: white to off-white solid
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in DMSO (up to 50 mg/ml).
• PKA: 6.1; 6.8(at 25℃)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months
• CAS DataBase Reference: Rosiglitazone maleate(CAS DataBase Reference)
• NIST Chemistry Reference: Rosiglitazone maleate(155141-29-0)
• EPA Substance Registry System: Rosiglitazone maleate(155141-29-0)

Safety Data

• Hazard Codes: Xi
• Statements: 20/21/22-36/38
• Safety Statements: 24/25-37/39-26
• WGK Germany: 3
• Hazardous Substances Data: 155141-29-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Rosiglitazone maleate is used as an insulin sensitizer for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It helps in improving blood sugar control and reducing the exogenous dose of insulin needed to achieve glycemic control in patients with type II diabetes.
Used in Antidiabetic Drug Development:
Rosiglitazone maleate is used as a thiazole alkanes antidiabetic drug, which is part of the thiazolidinediones (TZDs) group. It acts as a potent and selective PPARγ ligand, activating PPARγ1 and PPARγ2 with EC50 values of approximately 30 nM and 100 nM, respectively. This activation helps in normalizing glucose metabolism and improving insulin sensitivity.
Used in Research and Development:
Rosiglitazone maleate is used as a reference compound for the development of new drugs targeting PPARγ. Its potent agonist activity and selectivity make it a valuable tool for studying the role of PPARγ in various diseases and for developing new therapeutic strategies.
Used in Cell Differentiation Studies:
Rosiglitazone maleate is used to promote the differentiation of C3H10T1/2 stem cells into adipocytes. This application helps in understanding the role of PPARγ in adipose tissue differentiation and its potential implications in the treatment of obesity and related metabolic disorders.
Chemical Properties:
Rosiglitazone maleate is a white to off-white solid with a Kd value of approximately 43 nM for PPARγ. It does not induce the activity of P4503A4, unlike troglitazone, and has been shown to block estrogen synthesis by interfering with androgen binding to aromatase without affecting aromatase mRNA or protein expression.

Originator

SmithKline Beecham (US)

Indications

Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus.

References

1) Cantello et al. (1994), [[omega-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents; J. Med. Chem., 37 3977 2) Lehmann et al. (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPARgamma); J. Biol. Chem., 270 12953 3) Wilson et al. (1996), The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones; J. Med. Chem., 39 665 4) Haruya et al. (2012), PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein; Cell Metab., 15 395 5) Ruiz-Ojeda et al. (2016), Cell Models and their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review; Int. J. Mol. Sci., 17 E1040

InChI:InChI=1/C18H19N3O3S.C4H4O4/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15;5-3(6)1-2-4(7)8/h2-9,15H,10-12H2,1H3,(H,20,22,23);1-2H,(H,5,6)(H,7,8)/b;2-1-

Upstream product

• 110-16-7 maleic acid 
• 122320-73-4 rosiglitazone 

Downstream Products

• 956239-35-3 2-N-{5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione}-butanedioic acid 

Relevant articles and documents

Process for the Preparation of Intermediates of Rosiglitazone, Rosiglitazone and New Polymorphic Forms Thereof

The invention relates to a polymorphic form of 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene)-2,4-thiazolidinedione (Formula (I)): to a process for its preparation and to the use of such compound for preparing rosiglitazone in the form of a free base or a salt thereof. The invention also relates to a polymorphic form of rosiglitazone in the form of a free base, to a process for its preparation and to the use of such polymorph for preparing a salt of rosiglitazone. The invention also relates to a process of preparing a polymorphic form of a rosiglitazone salt.

PREPARATION OF ROSIGLITAZONE AND ITS SALTS

The present invention relates to rosiglitazone and its pharmaceutically acceptable salts free of at least one of the process related impurities, in particular the dehydro and the succinic acid impurities of rosiglitazone, wherein said impurities are present in an amount of about 05 mg to not more than about 15 mg, and processes for their preparation.

A PROCESS FOR THE CRYSTALLIZATION OF ROSIGLITAZONE AND ITS DERIVATIVES FROM MIXED SOLVENTS

Crystallization of rosiglitazone of formula (I), its penultimate of formula (II), or salts with acids of formula (III), wherein HX stands for a mineral or carboxylic acid, is carried out from mixed organic solvents, consisting of mixtures of carboxylic acids, particularly formic acid, acetic acid or propionic acid, with aliphatic alcohols, particularly methanol, ethanol, 1-propanol, 2- propanol, butanols or amyl alcohols.

NEW POLYMORPHOUS FORM OF ROSIGLITAZONE MALEATE

A new polymorphous crystalline form of rosiglitazone maleate, called form V, and the methods for obtaining it are described and characterized. Rosiglitazone maleate may be obtained in the form of the single polymorph V by mixing an approximately equimolar mixture of rosiglitazone base and maleic acid into a mixture of alcohols and water, heating the mixture under reflux and subsequently cooling it to ambient temperature.

PROCESS FOR PREPARING THIAZOLIDINEDIONES

This invention provides a process for reducing an exocyclic double bond at the 5-position of a thiazolidinedione moiety of a thiazolidinedione precursor comprising the steps of: a) preparing a solution or suspension of the thiazolidinedione precursor in a non-ether solvent medium with a base, and b) combining the solution or suspension with a dithionite source. Preferred solvent media include aqueous N,N-dimethylformamide. Sodium dithionite is a preferred dithionite source. In particular the application discloses preparation processes for Pioglitazone, Rosilitazone and Troglitazone.

NOVEL CO-PRECIPITATE

A novel coprecipitate of amorphous rosiglitazone maleate with a pharmaceutically acceptable carrier, e.g. polyvinylpyrolidone, mannitol, lactose, methylcellulose, cyclodextrin or silicon dioxide, a process for the preparation of said novel co-precipitate and the use of said novel coprecipitate of amorphous rosiglitazone with a pharmaceutically acceptable carrier in the treatment and / or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof, are disclosed. A novel solid solution of rosiglitazone maleate with a pharmaceutically acceptable carrier, preferably with polyethyelene glycol PEG from 4000 to 40.000 of average mol. wt., a process for the preparation thereof and use are disclosed. A novel coprecipitate of amorphous rosiglitazone maleate with a pharmaceutically acceptable carrier and a novel solid solution of rosiglitazone maleate with a pharmaceutically acceptable inert carrier are stable and may be particularly suitable for bulk preparation, handling and formulation advantages.

A PROCESS FOR PURIFICATION

The present invention provides a process for purification of pharmaceutically active compounds selected from the group consisting of thiazolidinedione derivatives and trans-3-Ethyl-2,5-dihydro-4-methyl-N- [2-[4-[[[[(4-methylcyclohexyl)amino] carbonyl] amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide comprising extraction in a solvent comprising an alkanol (C1-C4) and ammonia.

AMORPHOUS FORM OF ROSIGLITAZONE MALEATE AND PROCESS FOR PREPARATION THEREOF

An amorphous rosiglitazone maleate and its preparation as well as uses thereof for a pharmaceutical composition and a method for medical treatment including combination therapy are described.

Novel polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino[ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation

This invention relates to novel polymorphic/pseudopolymorphic forms of 5-[4-[2[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate having formula (I). The invention also relates to a pharmaceutical composition comprising the novel polymorphic form or their mixture and a pharmaceutically acceptable carrier. The polymorphic forms of the present invention are more active, as antidiabetic agent, than the hitherto known 5-[4-[2-[N-(2-methyl-N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate.