146062-44-4

Basic information

• Product Name: Hydroxypioglitazone
• Synonyms: HYDROXYPIOGLITAZONE;5-[[4-[2-[5-(1-HYDROXYETHYL)-2-PYRIDINYL]ETHOXY] PHENYL]METHYL]-2,4-THIAZOLIDINEDIONE;Hydroxy Pioglitazone (M-IV) ;Pioglitazone, hydroxy M-IV;Hydroxy Pioglitazone Solution, 100ppm;Pioglitazone M4 Metabolite
• CAS NO: 146062-44-4
• Molecular Formula: C₁₉H₂₀N₂O₄S
• Molecular Weight: 372.44
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 146062-44-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 157-1580C
• Boiling Point: 627.6 °C at 760 mmHg
• Flash Point: 333.4 °C
• Appearance: Off-White Solid
• Density: 1.325 g/cm³
• Vapor Pressure: 1.28E-16mmHg at 25°C
• Refractive Index: 1.628
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated)
• Stability: Hygroscopic
• CAS DataBase Reference: Hydroxypioglitazone(CAS DataBase Reference)
• NIST Chemistry Reference: Hydroxypioglitazone(146062-44-4)
• EPA Substance Registry System: Hydroxypioglitazone(146062-44-4)

Safety Data

• Hazardous Substances Data: 146062-44-4(Hazardous Substances Data)

Usage

Description

Hydroxy pioglitazone is a major metabolite of the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone (Item Nos. 71745 | 22263 | 10028). It is formed from pioglitazone by the cytochrome P450 (CYP) isoform CYP2C8 with minor contributions from CYP3A4. Hydroxy pioglitazone binds to PPARγ (Ki = 1.2 μM) and activates PPARγ in a time-resolved FRET (TR-FRET) assay (EC50 = 2.1 μM).

Chemical Properties

Off-White Solid

Uses

A metabolite of Pioglitazone (P471000).

InChI:InChI=1/C19H20N2O4S/c1-12(22)14-4-5-15(20-11-14)8-9-25-16-6-2-13(3-7-16)10-17-18(23)21-19(24)26-17/h2-7,11-12,17,22H,8-10H2,1H3,(H,21,23,24)

Upstream product

• 146062-60-4 methyl 2-bromo-3-<4-<2-<5-(1-memthoxymethoxyethyl)-2-pyridyl>ethoxy>phenyl>propionate 
• 146062-59-1 5-(1-methoxymethoxyethyl)-2-<2-(4-nitrophenoxy)ethyl>pyridine 
• 184766-25-4 4-{2-[5-(1-methoxymethoxy-ethyl)-pyridin-2-yl]-ethoxy}benzaldehyde 
• 146062-58-0 2-<5-(1-methoxymethoxyethyl)-2-pyridyl>ethanol 
• 146062-57-9 3-(1-(methoxymethoxy)ethyl)-6-methylpyridine 
• 21683-58-9 ethyl 3-(2-methyl-5-pyridinyl)-3-oxopropanoate 
• 5470-70-2 Methyl 6-methylnicotinate 
• 56019-64-8 5-(1-hydroxyethyl)-2-methylpyridine 
• 36357-38-7 1-(6-methyl-pyridin-3-yl)-ethanone 
• 184766-39-0 5-(4-(2-(5-(1-(methoxymethoxy)ethyl)pyridin-2-yl)ethoxy)benzyl)thiazolidine-2,4-dione 
• 1026292-59-0 2-Imino-5-(4-{2-[5-(1-methoxymethoxy-ethyl)-pyridin-2-yl]-ethoxy}-benzyl)-thiazolidin-4-one 

Downstream Products

• 146062-45-5 Ketopioglitazone 

Relevant articles and documents

PROCESS FOR PREPARING 5-[[4-[2-[5-(1-HYDROXYETHYL)-2-PYRIDINYL]ETHOXY]PHENYL]METHYL]-2,4-THIAZOLIDINEDIONE AND SALTS THEREOF

The disclosure provides a process of making the compound of Formula I, and pharmaceutically acceptable salts thereof: and the process of making the intermediate of Formula III: wherein PG is as defined as set forth in the specification.

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).

Thiazolidinedione derivatives, production and use thereof

A thiazolidinedione compound of the formula STR1 wherein X,Q are as defined in the specification. The compounds are used for treating diabetes.