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Details

Stereochemistry RACEMIC
Molecular Formula C18H18N3O3S.C5H14NO
Molecular Weight 460.59
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROSIGLITAZONE CHOLINATE

SMILES

C[N+](C)(C)CCO.CN(CCOC1=CC=C(CC2SC(=O)[N-]C2=O)C=C1)C3=CC=CC=N3

InChI

InChIKey=JKQQOKOTRFSCBL-UHFFFAOYSA-M
InChI=1S/C18H19N3O3S.C5H14NO/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;1-6(2,3)4-5-7/h2-9,15H,10-12H2,1H3,(H,20,22,23);7H,4-5H2,1-3H3/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C18H19N3O3S
Molecular Weight 357.427
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula C5H13NO
Molecular Weight 103.1628
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/mtm/rosiglitazone.html http://www.rxlist.com/avandia-drug.htm http://www.wikidoc.org/index.php/Rosiglitazone

Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. It is FDA approved for the treatment of as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Inhibitors of CYP2C8 (e.g., gemfibrozil) may increase rosiglitazone levels; inducers of CYP2C8 (e.g., rifampin) may decrease rosiglitazone levels. Common adverse reactions include edema, weight gain, and headache.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AVANDIA

Approved Use

After consultation with a healthcare professional who has considered and advised the patient of the risks and benefits of rosiglitazone, AVANDAMET® is indicated as an adjunct to diet and exercise to improve glycemic control when treatment with both rosiglitazone and metformin is appropriate in adults with type 2 diabetes mellitus who either are: already taking rosiglitazone, or not already taking rosiglitazone and unable to achieve glycemic control on other diabetes medications and, in consultation with their healthcare provider, have decided not to take pioglitazone (ACTOS®) or pioglitazone-containing products (ACTOPLUS MET®, ACTOPLUS MET XR®, DUETACT®) for medical reasons. Other Important Limitations of Use: Due to its mechanism of action, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDAMET should not be used in patients with type 1 diabetes. Coadministration of AVANDAMET with insulin is not recommended [see Warnings and Precautions (5.2, 5.3)

Launch Date

1999
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
432 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
598 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2890 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
2971 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.59 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
3.37 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
DLT: Headache, Malaise...
Disc. AE: Pain in leg...
Dose limiting toxicities:
Headache (3.1%)
Malaise (3.1%)
Oedema legs (9.4%)
AEs leading to
discontinuation/dose reduction:
Pain in leg (3.1%)
Sources: Page: p.105
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources: Page: p.73,74
unhealthy, 60
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 60
Sex: M
Population Size: 1
Sources: Page: p.73,74
Disc. AE: Macular edema...
AEs leading to
discontinuation/dose reduction:
Macular edema
Sources: Page: p.73,74
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Disc. AE: Congestive heart failure, Myocardial ischemia...
AEs leading to
discontinuation/dose reduction:
Congestive heart failure
Myocardial ischemia (2%)
Fluid retention
Edema
Weight gain
Anemia
Macular edema
Fracture bone
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Headache 3.1%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Malaise 3.1%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Pain in leg 3.1%
Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Oedema legs 9.4%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Macular edema Disc. AE
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources: Page: p.73,74
unhealthy, 60
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 60
Sex: M
Population Size: 1
Sources: Page: p.73,74
Myocardial ischemia 2%
Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Anemia Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Congestive heart failure Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Edema Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Fluid retention Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Fracture bone Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Macular edema Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Weight gain Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.
2001 Nov 20
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation.
2002 Apr
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons.
2002 Jan 11
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.
2002 Jul
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro.
2002 Jun
AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.
2002 Nov
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.
2003 Apr
PPAR gamma-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNF alpha secretion is not mediated by PTEN regulation.
2003 Apr 11
15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia.
2003 Apr 25
Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect.
2003 Aug 15
Expression of phosphoenolpyruvate carboxykinase gene in human adipose tissue: induction by rosiglitazone and genetic analyses of the adipocyte-specific region of the promoter in type 2 diabetes.
2003 Dec
A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.
2003 Feb 7
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes.
2003 Jan 3
Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.
2003 Jul
PPARgamma ligands induce prostaglandin production in vascular smooth muscle cells: indomethacin acts as a peroxisome proliferator-activated receptor-gamma antagonist.
2003 Oct
Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells.
2003 Oct 15
Rosiglitazone inhibits the insulin-mediated increase in PAI-1 secretion in human abdominal subcutaneous adipocytes.
2003 Sep
Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes.
2004 Aug
The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines.
2004 Aug
Decreased expression of peroxisome proliferator activated receptor gamma in cftr-/- mice.
2004 Aug
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension].
2004 Dec
Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.
2004 Dec 1
A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist.
2004 Dec 15
Bone is a target for the antidiabetic compound rosiglitazone.
2004 Jan
Evidence for a potent antiinflammatory effect of rosiglitazone.
2004 Jun
Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis.
2004 Jun 4
Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy.
2004 Mar 23
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.
2004 May
Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer.
2004 May 15
Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone.
2004 Nov
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism.
2004 Nov
Chronic heart failure-related interventions after starting rosiglitazone in patients receiving insulin.
2004 Oct
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.
2004 Oct 22
Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys.
2004 Sep
The antidiabetic agent rosiglitazone upregulates SERCA2 and enhances TNF-alpha- and LPS-induced NF-kappaB-dependent transcription and TNF-alpha-induced IL-6 secretion in ventricular myocytes.
2005
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.
2005 Aug
Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro.
2005 Feb
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.
2005 Feb
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines.
2005 Feb
The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.
2005 Mar
Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPARgamma-independent mechanism.
2005 Mar
Development of a complex scintillation proximity assay for high-throughput screening of PPARgamma modulators.
2005 Mar
Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.
2005 Mar
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.
2005 Mar
The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.
2005 May
Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma.
2005 May
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.
2005 May
Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1.
2005 Sep
Patents

Sample Use Guides

Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.
Route of Administration: Oral
Rosiglitazone treatment (5 uM) prevents NO and prostacyclin overproduction by inhibiting microparticles-induced iNOS and COX-2 expression.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:55:57 GMT 2023
Edited
by admin
on Fri Dec 15 18:55:57 GMT 2023
Record UNII
386X2T4SQV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROSIGLITAZONE CHOLINATE
Common Name English
ETHANAMINIUM, 2-HYDROXY-N,N,N-TRIMETHYL-, ((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-2,4-THIAZOLIDINEDIONATE (1:1)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C98241
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
NCI_THESAURUS C1934
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C96870
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
PRIMARY
PUBCHEM
15981010
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
PRIMARY
FDA UNII
386X2T4SQV
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
PRIMARY
CAS
920338-48-3
Created by admin on Fri Dec 15 18:55:57 GMT 2023 , Edited by admin on Fri Dec 15 18:55:57 GMT 2023
PRIMARY
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