101931-00-4

Basic information

• Product Name: Hydroxy Pioglitazone (M-II) (Mixture of Diastereomers)
• Synonyms: Hydroxy Pioglitazone (M-II) (Mixture of Diastereomers);Pioglitazone, hydroxyl M-II;2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)-2-hydroxyethoxy]phenyl]Methyl]-;Pioglitazone Hydroxy M-II;Pioglitazone M2 Metabolite;5-(4-(2-(5-Ethylpyridin-2-yl)-2-hydroxyethoxy)benzyl)thiazolidine-2,4-dione
• CAS NO: 101931-00-4
• Molecular Formula: C₁₉H₂₀N₂O₄S
• Molecular Weight: 372.443
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 101931-00-4.mol

Chemical Properties

• Melting Point: 125-140 (sub)
• Boiling Point: 627.617°C at 760 mmHg
• Flash Point: 333.371°C
• Appearance: /
• Density: 1.325g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.628
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Hydroxy Pioglitazone (M-II) (Mixture of Diastereomers)(CAS DataBase Reference)
• NIST Chemistry Reference: Hydroxy Pioglitazone (M-II) (Mixture of Diastereomers)(101931-00-4)
• EPA Substance Registry System: Hydroxy Pioglitazone (M-II) (Mixture of Diastereomers)(101931-00-4)

Safety Data

• Hazardous Substances Data: 101931-00-4(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

A metabolite of Pioglitazone (P471000).

InChI:InChI=1/C19H20N2O4S/c1-2-12-5-8-15(20-10-12)16(22)11-25-14-6-3-13(4-7-14)9-17-18(23)21-19(24)26-17/h3-8,10,16-17,22H,2,9,11H2,1H3,(H,21,23,24)

Upstream product

• 646519-88-2 5-{4-[2-chloro-2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-2,4-thiazolidene dione 
• 646519-81-5 2-bromo-1-(5-ethylpyridin-2-yl)ethanol 
• 646519-84-8 5-{4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzylidene}-2,4-thiazolidene dione 
• 471295-98-4 4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzaldehyde 
• 123-08-0 4-hydroxy-benzaldehyde 
• 646519-82-6 5-ethyl-2-[2-oxo-(1,3,2)dioxathiolan-4-yl]pyridine 
• 90643-32-6 2-(5-ethyl-1-oxypyridin-2-yl)ethanol 
• 646519-94-0 5-{4-[2-chloro-2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione 
• 768-61-6 2-hydroxymethyl-5-ethyl pyridine 
• 5408-74-2 5-ethyl-2-vinyl-pyridine 
• 471295-99-5 (5Z)-5-{4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzylidene}-1,3-thiazolidine-2,4-dione 
• 350-46-9 4-Fluoronitrobenzene 
• 101931-09-3 methyl 3-{4-[2-acetoxy-2-(5-ethyl-2-pyridyl) ethoxy]phenyl}-2-bromopropionate 
• 145350-19-2 methyl 2-bromo-3-{4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl}propionate N-oxide 

Downstream Products

• 146062-49-9 rac-5-({p-[2-(5-ethylpyridin-2-yl)-2-oxoethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione 
• 74772-78-4 5-(4-hydroxybenzyl)-2,4-thiazolidinedione 
• 105355-27-9 Pioglitazone 
• 646519-90-6 5-{4-[2-(5-ethylpyridin-2-yl)-2-mesylethoxy]benzylidene}-2,4-thiazolidene dione 
• 646519-92-8 5-{4-[2-(5-ethylpyridin-2-yl)-2-tosylethoxy]benzylidene}-2,4-thiazolidene dione 
• 646519-94-0 5-{4-[2-chloro-2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione 
• 144809-28-9 5-{4-[2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione 
• 112529-15-4 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride 
• 646519-98-4 5-{4-[2-bromo-2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione 
• 471295-98-4 4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzaldehyde 
• 5408-74-2 5-ethyl-2-vinyl-pyridine 
• 646519-89-3 5-{4-[2-chloro-2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-2,4-thiazolidene dione hydrochloride 

Relevant articles and documents

NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES

A novel process for preparing thiazolidinediones, preferably Pioglitazone, as described. Also described are novel intermediates involved in its synthesis and process for their preparation and use in medicine.

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.

A NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES.

A novel process for preparing thiazolidinediones, preferably Pioglitazone, are described. Also described are novel intermediates involved in its synthesis and process for their preparation and use in medicine.

Process development and scale-up of the potential thiazolidinedione antidiabetic candidate PNU-91325

An efficient six-step synthesis has been developed for the preparation of the thiazolidinedione analogue PNU-91325 (3) from the commercially available olefin 12. This process involves a novel epoxide ring opening with a deactivated phenol under phase-transfer conditions. Significant improvements were made in the oxidation of a secondary alcohol to the ketone and the 1,4-reduction of an enone from a previous process. Overall, this route allows for the preparation of PNU-91325 in 25% yield.

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).

Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones

The synthesis of a series of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones is described. These compounds were evaluated for hypoglycemic and hypolipidemic activities in genetically obese and diabetic mice, yellow KK. 2-(2-Pyridyl)alkoxy derivatives were found to have much better hypoglycemic and hypolipidemic activities than 2-(3-pyridyl)- and 2-(4-pyridyl)alkoxy derivatives or even the previously reported compound, ciglitazone. The introduction of a hydroxyl group at the 2-position of the ethoxy chain potentiated the activities. Among the potent compounds, pioglitazone (AD-4833) was selected as a candidate compound.

2,4-thiazolidinediones

Thiazolidinedione derivatives of the general formula: STR1 wherein R1 and R2 are the same or different and each represent hydrogen or a lower alkyl group; R3 is hydrogen or an acyl group; n is 0 or 1 and salts thereof are novel compounds, which exhibit in mammals blood sugar- and lipid-lowering activity, and are of value as a therapeutic agent for diabetes and therapeutic agent for hyperlipemia.