145350-09-0

Basic information

• Product Name: Pioglitazone N-Oxide
• Synonyms: 5-[[4-[2-(5-Ethyl-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione N-Oxide;Pioglitazone N-Oxide;2-(2-(4-((2,4-dioxothiazolidin-5-yl)methyl)phenoxy)ethyl)-5-ethylpyridine 1-oxide
• CAS NO: 145350-09-0
• Molecular Formula: C₁₉H₂₀N₂O₄S
• Molecular Weight: 372.443
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Heterocycles;Sulfur & Selenium Compounds
• Mol File: 145350-09-0.mol
• Article Data: 5

Chemical Properties

• Melting Point: 158-160°C
• Boiling Point: 666.324 °C at 760 mmHg
• Flash Point: 356.78 °C
• Appearance: white solid
• Density: 1.329 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.64
• Storage Temp.: -20?C Freezer, Under Inert Atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.34±0.50(Predicted)
• CAS DataBase Reference: Pioglitazone N-Oxide(CAS DataBase Reference)
• NIST Chemistry Reference: Pioglitazone N-Oxide(145350-09-0)
• EPA Substance Registry System: Pioglitazone N-Oxide(145350-09-0)

Safety Data

• Hazardous Substances Data: 145350-09-0(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

A metabolite of Pioglitazone (P471000).

InChI:InChI=1S/C19H20N2O3S.ClH/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);1H

Upstream product

• 112529-15-4 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride 
• 105355-27-9 Pioglitazone 

Downstream Products

• 146062-49-9 rac-5-({p-[2-(5-ethylpyridin-2-yl)-2-oxoethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione 
• 101931-00-4 5-{4-[2-(5-ethyl-pyridin-2-yl)-2-hydroxyethoxy]benzyl}-2,4-thiazolidinedione 

Relevant articles and documents

Microbiological N-deoxygenation and C-oxygenation of pioglitazone-N-oxide in a single fermentation

Oxygenation of pioglitazone-N-oxide by a microorganism isolated from soil was accompanied by N-deoxygenation to produce the pioglitazone metabolites 5-[4-[2-[5-(1-hydroxyethyl)-2-pyridyl]ethoxy]benzyl]-2,4-thiazolidinedione and 5-[4-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione. The oxygenating/deoxygenating organism has been characterized as Streptomyces hygroscopicus strain 02179 (UC 11099). The culture has been deposited with Agricultural Research Service, USDA, with accession number NRRL 18975.

5-DEUTERO-2,4-THIAZOLIDINEDIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

The invention provides 5-deuterium-enriched 2,4-thiazolidinediones (e.g., 5-[4-[2-(5-ethyl-2-pyridyl)-2-oxoethoxy]benzyl]-5-deutero-thiazolidine-2,4-dione), deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.

Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone

Pioglitazone (5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4- thiazolidinedione, 2) is a prototypical antidiabetic thiazolidinedione that had been evaluated for possible clinical development. Metabolites 6-9 have been identified after dosing of rats and dogs. Ketone 10 has not yet been identified as a metabolite but has been added to the list as a putative metabolite by analogy to alcohol 6 and ketone 7. We have developed improved syntheses of pioglitazone (2) metabolites 6-9 and the putative metabolite ketone 10. These entities have been compared in the KKA(y) mouse model of human type-II diabetes to pioglitazone (2). Ketone 10 has proven to be the most potent of these thiazolidinediones in this in vivo assay. When 6-10 were compared in vitro in the 3T3-L1 cell line to 2, for their ability to augment insulin-stimulated lipogenesis, 10 was again the most potent compound with 6, 7, and 9 roughly equivalent to 2. These data suggest that metabolites 6, 7, and 9 are likely to contribute to the pharmacological activity of pioglitazone (2), as had been previously reported for ciglitazone (1).