155141-29-0 Usage
Description
Rosiglitazone maleate, belongs to a novel class of thiazolidine diones
launched for the treatment of non-insulin-dependent diabetes mellitus (NIDDM),
a disease characterized by a pancreatic β-cell defect and insulin resistance in
the liver and peripheral tissues. The racemic base can be obtained by
KnSvenagel condensation between 2, 4-thiazolidinedione and the corresponding
4-substituted benzaldehyde (itself prepared in 2 steps from 2-chloropyridine),
followed by reduction of the benzylidene. Rosiglitazone was shown to be a
potent agonist of peroxisome proliferator activated receptor-gamma (PPARgamma),
a nuclear receptor involved in the differentiation of adipose tissue,
without activating liver PPAR-alpha receptors. This activation of PPAR-gamma
could mediate the down-regulation of leptin gene expression. In animal models,
Rosiglitazone has been shown to normalize glucose metabolism and reduce the
exogenous dose of insulin needed to achieve glycemic control. In patients with
Type II diabetes, daily doses (4 or 8 mg) of Rosiglitazone significantly improved
blood sugar control without affecting cardiac structure or function.
Chemical Properties
White To Off-White Solid
Originator
SmithKline Beecham (US)
Uses
Different sources of media describe the Uses of 155141-29-0 differently. You can refer to the following data:
1. Insulin sensitizer; binds to peroxisome proliferator activated receptor gamma (PPAR- γ).
2. Thiazole alkanes antidiabetic drug
3. Thiazolidinediones (TZDs) are a group of structurally related peroxisome proliferator-activated receptor γ (PPARγ) agonists with antidiabetic actions in vivo. Rosiglitazone is a prototypical TZD that has served as a reference compound for this class. It is a potent and selective PPARγ ligand that binds to the PPARγ ligand-binding domain with a Kd value of 43 nM. It activates luciferase-based expression constructs PPARγ1 and PPARγ2 with EC50 values of approximately 30 nM and 100 nM, respectively. Rosiglitazone is active in vivo as an antidiabetic agent in the ob/ob mouse model, and has been used as an oral hypoglycemic agent in the treatment of type 2 diabetes in humans for many years.[Cayman Chemical]
Indications
Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus.
General Description
A thiazolidinedione compound that acts as an anti-diabetic agent and serves as a potent and selective agonist of peroxisome proliferator-activated receptor-g (PPARg) (Kd ~40 nM) in fat cells. Shown to reduce fatty acid uptake and ameliorate lipid metabolism and insulin resistance in animal models of type II diabetes. Reported to activate both a1- and a2-containing AMPK complexes. Unlike troglitazone, it does not induce the activity of P4503A4. Significantly improves the differentiation of C3H10T1/2 stem cells into adipocytes. Shown to block estrogen synthesis by interfering with androgen binding to aromatase, but without affecting aromatase mRNA or protein expression.
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
Check Digit Verification of cas no
The CAS Registry Mumber 155141-29-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,5,1,4 and 1 respectively; the second part has 2 digits, 2 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 155141-29:
(8*1)+(7*5)+(6*5)+(5*1)+(4*4)+(3*1)+(2*2)+(1*9)=110
110 % 10 = 0
So 155141-29-0 is a valid CAS Registry Number.
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-
155141-29-0Relevant articles and documents
Process for the Preparation of Intermediates of Rosiglitazone, Rosiglitazone and New Polymorphic Forms Thereof
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Page/Page column 5-6, (2009/09/28)
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.
A PROCESS FOR THE CRYSTALLIZATION OF ROSIGLITAZONE AND ITS DERIVATIVES FROM MIXED SOLVENTS
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Page/Page column 20, (2008/06/13)
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.
PROCESS
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Page/Page column 15, (2008/06/13)
The present invention relates to processes for the preparation of rosiglitazone, rosiglitazone prepared thereby and pharmaceutical compositions and therapeutic uses thereof, and methods of treatment employing the same.
