CAS 122320-73-4|Rosiglitazone|rosiglitazone|Avandia|BRL-49653|5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione|rosiglitazone|Rosiglizole|Rosiglitazone maleate|Ros...

General Information

Structure

Molecular Formula

C₁₈H₁₉N₃O₃S

Molecular Mass

357.42676

Exact Mass

357.11471248

Charge

0

InChI

InChI=1S/C18H19N3O3S/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/h2-9,15H,10-12H2,1H3,(H,20,22,23)

InChIKey

YASAKCUCGLMORW-UHFFFAOYSA-N

Canonic Smiles

O=C1NC(=O)C(S1)Cc1ccc(cc1)OCCN(c1ccccn1)C

Isomeric Smiles

S1C(Cc2ccc(OCCN(c3ncccc3)C)cc2)C(=O)NC1=O

Calculated Properties

JChem

LogD (pH = 7.4)

2.69

LogD (pH = 5.5)

2.18

Log P

2.80

Rotatable Bonds

7

H Donor

1

H Acceptors

5

Lipinski's Rule of Five

true

Acid pKa

7.37

Polar Surface Area

71.53

Polarizability

37.50

Molar Refractivity

97.79

LOG S

-4.26

Data Source

Academic Data

Commercial Catalog

Data Source

Names and Identifiers

Synonyms

RosiglitazoneAvandiaBRL-49653rosiglitazoneRosiglitazone maleateRosigliazone maleateRosiglitazone5-[[4-[2-(Methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione5-(4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dioneBRL-496535-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedionerosiglitazone

IUPAC Traditional name

rosiglitazone

IUPAC name

5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione

Brand Name

RosiglizoleAvandia

International Nonproprietary Name (INN)

rosiglitazonumrosiglitazonerosiglitazona

Names and Identifiers

Registration numbers

MDL Number

MFCD00871760

CAS Number

122320-73-4

PubChem SID

1609637584650455649836665

PubChem CID

77999

Patent number

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

BKMS React Database

340483445

UniProt Database

O70302Q9ESN4Q8K4F5P0C548P56198

NURSA Database

10.1621/ETHEsG15w910.1621/9FBUklA3Z310.1621/sZmbHJb4Eb10.1621/7r5L8uWTSO10.1621/TPgATkirzS10.1621/HslyUoSYAs10.1621/hLnw2RmSWG10.1621/rP497GvEr210.1621/aYCyHF2ig410.1621/p3ZSUojETc10.1621/dYqMBEjruH10.1621/3btG3BUf5b10.1621/HA4DTjou1z10.1621/dEYWKlZ72H10.1621/9IFwN8xkBn10.1621/kW1GZB1BZ6

ArrayExpress (Gene Expression Altlas)

E-GEOD-5679E-MTAB-6796E-GEOD-30147

Reactom Database

R-HSA-400509R-HSA-749448R-HSA-560491R-HSA-379048R-HSA-8944099R-HSA-560510R-HSA-383313R-HSA-400434R-HSA-560498R-HSA-1183058R-HSA-560517R-HSA-416530R-HSA-1183003R-HSA-749452R-HSA-560472

BRENDA Database

1.1.1.1461.6.3.16.2.1.206.2.1.32.6.1.12.3.1.151.1.1.212.7.1.302.7.1.333.1.1.231.14.11.21.3.8.71.1.1.1412.7.11.31

PubMed Citation Links

319367293365078633746608172593703223464230225267

Drug Central Database

2,405

Beilstein Number

7082202

BRENDA Ligand Database

DrugBank ID

SABIO-RK Database

ACToR Database

SureChEMBL Database

CompTox Database

Wikipedia Title

CHEBI ID

CHEMBL

MetaboLights Database

MTBLS1191MTBLS2384

BindingDB Database

50030474

LINCS Database

LSM-1949

Registration numbers

Properties

Physical Property

Hydrophobicity(logP)

2.4

Solubility

DMSO: ≥10 mg/mL

Apperance

powder

Pharmacology Properties

Target

PPAR

Product Information

Salt Data

Free Base

Purity

≥98% (HPLC)

95+%

Linear Formula

C18H19N3O3S

Safety Information

Storage Condition

-20°C

MSDS Link

Download link

German water hazard class

3

Storage Temperature

2-8°C

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00412

Drug Groups

approved; investigational

Description

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl).

Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action.

Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone.

Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway.

Indication

For the treatment of Type II diabetes mellitus

Pharmacology

Rosiglitazone, a member of the drug group known as the thiazolidinediones or "insulin sensitizers", is not chemically or functionally related to the alpha-glucosidase inhibitors, the biguanides, or the sulfonylureas. Rosiglitazone targets insulin resistance and, hence, is used alone or with metformine or sulfonylurea to improve glycemic control in patients with type 2 diabetes mellitus.

Toxicity

Side effects include fluid retention, congestive heart failure (CHF), liver disease

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic. Rosiglitazone is extensively metabolized in the liver to inactive metabolites via N-demethylation, hydroxylation, and conjugation with sulfate and glucuronic acid. In vitro data have shown that Cytochrome (CYP) P450 isoenzyme 2C8 (CYP2C8) and to a minor extent CYP2C9 are involved in the hepatic metabolism of rosiglitazone.

Absorption

The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in C_max and a delay in T_max (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food.

Half Life

3-4 hours

Protein Binding

99.8% bound to plasma proteins, primarily albumin.

Elimination

Following oral or intravenous administration of [14C]rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively.

Distribution

* 6 L

Clearance

* Oral cl=3.03 +/- 0.87 L/hr [1 mg Fasting]
* Oral cl=2.89 +/- 0.71 L/hr [2 mg Fasting]
* Oral cl=2.85 +/- 0.69 L/hr [8 mg Fasting]
* Oral cl=2.97 +/- 0.81 L/hr [8 mg Fed]
* 3.15 L/hr [Population mean]

References

• Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P: Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35. [Pubmed]

• Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. Epub 2006 Dec 4. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [PDRhealth]

• [Drugs.com]

Selleck Chemicals

S2556

Research Area: Immunology
Biological Activity:
Rosiglitazone (Avandia) is a potent antihyperglycemic agent and a potent thiazolidinedione insulin sensitizer with IC50 of 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively. Rosiglitazone (Avandia) has recently been identified as a high-affinity ligand for PPARγ, a nuclear hormone receptor that is abundantly expressed in adipocytes and plays a central role as a regulator of terminal adipocyte differentiation. Rosiglitazone (Avandia) acts primarily by increasing insulin sensitivity. Rosiglitazone (Avandia) improves glycemic control while reducing circulating insulin levels. Rosiglitazone (Avandia) is a member of the thiazolidinedione class of drugs. They reduce glucose, fatty acid, and insulin blood concentrations. They work by binding to the peroxisome proliferator-activated receptors (PPARs). Thiazolidinediones enter the cell, bind to the nuclear receptors, and affect the expression of DNA. Rosiglitazone (Avandia, BRL-49653) also appears to have an anti-inflammatory effect in addition to its effect on insulin resistance. [1][2]

Sigma Aldrich

R2408

Biochem/physiol Actions
Rosiglitazone is a potent agonist for PPARγ with an EC50 of 43 nM for the human receptor. It is antidiabetic, working as an insulin sensitizer by binding to the PPARγ receptors in fat cells and making the cells more responsive to insulin.

Molecule Details

References

PubChem Literature

From Data Sources

• Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. Epub 2006 Dec 4. Pubmed

• Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P: Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35. Pubmed

•

• Young PW et al. J Pharmacol Exp Ther. 1998 Feb; 284(2):751-9.

References

Bioactivity

PubChem BioAssay

Bioactivity

Molecule

ID:295