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

• ChemBase ID: 1003
• Molecular Formular: C19H20N2O3S
• Molecular Mass: 356.4387
• Monoisotopic Mass: 356.11946351
• SMILES: S1C(Cc2ccc(OCCc3ncc(CC)cc3)cc2)C(=O)NC1=O
• Canonical SMILES: CCc1ccc(nc1)CCOc1ccc(cc1)CC1SC(=O)NC1=O
• InChI: InChI=1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23)
• InChIKey: HYAFETHFCAUJAY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
• IUPAC Traditional name: pioglitazone
• Brand Name: Actos; Actost; Glustin
• Synonyms: Pioglitazona [INN-Spanish]; Pioglitazone Hydrochloride; Pioglitazone [Ban:Inn]; Pioglitazonum [INN-Latin]; pioglitazone HCl; Pioglitazone; Actos

Database IDs

• CAS Number: 111025-46-8
• PubChem SID: 46507136; 160964466
• PubChem CID: 4829

CALCULATED PROPERTIES

JChem

• Acid pKa: 6.657649
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 3.1840525
• LogD (pH = 7.4): 2.7427685
• Log P: 3.3282487
• Molar Refractivity: 97.3908 cm^3
• Polarizability: 37.941406 Å^3
• Polar Surface Area: 68.29 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.17
• LOG S: -4.91
• Solubility (Water): 4.42e-03 g/l

PROPERTIES

Physical Property

• Solubility: mg/mL
• Hydrophobicity(logP): 2.3

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB01132

• Drug Groups: approved; investigational
• Description: Pioglitazone is used for the treatment of diabetes mellitus type 2. Pioglitazone selectively stimulates nuclear receptor peroxisone proliferator-activated receptor gamma (PPAR-gamma). It modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver.
• Indication: Treatment of Type II diabetes mellitus
• Pharmacology: Pioglitazone, 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. Pioglitazone targets insulin resistance and, hence, is used alone or in combination with insulin, metformin, or asulfonylurea as an antidiabetic agent.
• Toxicity: Hypogycemia; LD₅₀=mg/kg (orally in rat)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Following oral administration, in the fasting state, pioglitazone is first measurable in serum within 30 minutes, with peak concentrations observed within 2 hours. Food slightly delays the time to peak serum concentration to 3 to 4 hours, but does not alter the extent of absorption.
• Half Life: 3-7 hours
• Protein Binding: > 99%
• Elimination: Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.
• Distribution: * 0.63 ± 0.41 L/kg
• Clearance: * apparent cl=5 - 7 L/h [oral administration]
• References: Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR: Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E252-60. Epub 2003 Oct 21. [Pubmed] ; Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA: MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. [Pubmed] ; Lincoff AM, Wolski K, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S2590

Research Area: Metabolic Disease
Biological Activity:
Pioglitazone (Actos) is a selective peroxisome proliferator-activated receptor gamma stimulator. Pioglitazone (Actos) selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α. Pioglitazone (Actos) modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone (Actos) reduces insulin resistance in the liver and peripheral tissues. Pioglitazone (Actos) increases the expense of insulin-dependent glucose. Pioglitazone (Actos) decreases withdrawal of glucose from the liver. Pioglitazone (Actos) reduces quantity of glucose, insulin and glycated hemoglobin in the bloodstream. [1][2][3]References on Pioglitazone (Actos)[1] http://en.wikipedia.org/wiki/Pioglitazone, , [2] Drugs. , 2000 Aug, 60(2):333-43[3] Int J Clin Pract Suppl., 2001 Sep, (121):13-8

REFERENCES

• Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR: Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E252-60. Epub 2003 Oct 21. Pubmed
• Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA: MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. Pubmed
• Lincoff AM, Wolski K, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8. Pubmed
• http://www.selleckchem.com/products/pioglitazone-actos.html