111025-46-8

Basic information

• Product Name: Pioglitazone
• Synonyms: Pioglitazone;PIOGLITAZONE HCL(5-[[4-[2-(5-ETHYLPYRIDIN-2-YL)ETHOXY]PHENYL]METHYL]THIAZOLIDINE-2,4-DIONE, HCL);PINEPOLLEN;5-[4-[2-(5-Ethyl-2-pyridyl)ethoxy]benzyl]thiazolidine-2,4-dione;5-[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]benzyl]thiazolidine-2,4-dione;Pioglitazone (Actos);2,4-Thiazolidinedione,5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]Methyl]-;Pioglitazone 5-[[4-[2-(5-Ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• CAS NO: 111025-46-8
• Molecular Formula: C19H20N2O3S
• Molecular Weight: 356.44
• EINECS: 1308068-626-2
• Product Categories: APIS;LESCOL
• Mol File: 111025-46-8.mol

Chemical Properties

• Melting Point: 183-184 C
• Boiling Point: 575.4 °C at 760 mmHg
• Flash Point: 301.8 °C
• Appearance: Colorless needle crystal
• Density: 1.26 g/cm³
• Vapor Pressure: 3.03E-13mmHg at 25°C
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly, Heated)
• PKA: 6.35±0.50(Predicted)
• CAS DataBase Reference: Pioglitazone(CAS DataBase Reference)
• NIST Chemistry Reference: Pioglitazone(111025-46-8)
• EPA Substance Registry System: Pioglitazone(111025-46-8)

Safety Data

• Hazard Codes: F,C
• Statements: 11-34
• Safety Statements: 16-26-36/37/39-45
• Hazardous Substances Data: 111025-46-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Pioglitazone is used as an antihyperlipidemic agent for reducing hyperlipidemia in patients. It helps in lowering high levels of lipids in the blood, which is crucial for maintaining cardiovascular health.
Used in Diabetes Management:
Pioglitazone is used as an antidiabetic medication for patients with type 2 diabetes mellitus. It exhibits hypoglycemic activity by improving insulin sensitivity and glucose uptake in peripheral tissues, thereby helping in better blood sugar control.
Used in Anticancer Research:
Pioglitazone has been shown to reduce the number of lesions in a transgenic rat adenocarcinoma of prostate (TRAP) model. This suggests its potential use in cancer research and development for targeted therapies.
Used in Antidepressant-like Activity:
Pioglitazone has demonstrated antidepressant-like activity in a mouse model of chronic mild stress. It decreases the production of neuroinflammatory cytokines and reduces immobility in behavioral tests, indicating its potential use in the development of novel antidepressant therapies. However, this activity can be reversed by the PPARγ antagonist GW9662, highlighting the importance of PPARγ in its mechanism of action.

Originator

Actos ,Eli Lilly ,USA

Indications

Pioglitazone is approved for use as monotherapy and in conjunction with metformin, sulfonylureas, and insulin. It is taken once a day with or without food. Though pioglitazone may also cause a small increase in low-density lipoprotein concentrations, there is usually a modest decrease in triglyceride levels, but it unclear whether this has any clinical significance or persists in the long term.

Manufacturing Process

To a solution of 2-(5-ethyl-2-pyridyl)ethanol (53.0 g) and 4-fluoronitrobenzene (47.0 g) in DMF (500 ml) was added portionwise under ice-cooling 60% sodium hydride in oil (16.0 g). The mixture was stirred under ice-cooling for one hour, then at room temperature for 30 min, poured into water and extracted with ether. The ether layer was washed with water and dried (MgSO4). The solvent was evaporated off to give 4-[2-(5-ethyl-2pyridyl)ethoxy]nitrobenzene as crystals (62.0 g, 62.9%). Recrystallization from ether-hexane gave colorless prisms, melting point 53°-54°C.A solution of 4-[2-(5-ethyl-2-pyridyl)ethoxy]nitrobenzene (60.0 g) in methanol (500 ml) was hydrogenated at room temperature under one atmospheric pressure in the presence of 10% Pd-C (50% wet, 6.0 g). The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The residual oil was dissolved in acetone (500 ml)methanol (200 ml). To the solution was added a 47% HBr aqueous solution (152 g). The mixture was cooled, to which was added dropwise a solution of NaNO2 (17.3 g) in water (30 ml) at a temperature not higher than 5°C. The whole mixture was stirred at 5°C for 20 min, then methyl acrylate (112 g) was added thereto and the temperature was raised to 38°C. Cuprous oxide (2.0 g) was added to the mixture in small portions with vigorous stirring. The reaction mixture was stirred until nitrogen gas evolution ceased, and was concentrated under reduced pressure. The concentrate was made alkaline with concentrated aqueous ammonia, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4) The solvent was evaporated off to leave methyl 2-bromo-3-{4-[2-(5-ethyl-2pyridyl)ethoxy]phenyl}propionate as a crude oil (74.09 g, 85.7%).A mixture of the crude oil of methyl 2-bromo-3-{4-[2-(5-ethyl-2pyridyl)ethoxy]phenyl}propionate (73.0 g) thiourea (14.2 g), sodium acetate (15.3 g) and ethanol (500 ml) was stirred for 3 hours under reflux. The reaction mixture was concentrated under reduced pressure, and the concentrate was neutralized with a saturated aqueous solution of sodium hydrogencarbonate, to which were added water (200 ml) and ether (100 ml). The whole mixture was stirred for 10 min to yield 5-{4-[2-(5-ethyl-2pyridyl)ethoxy]benzyl}-2-imino-4-thiazolidinone as crystals (0.3 g, 523.0%). Recrystallization from methanol gave colorless prisms, melting point 187°188°C, dec.A solution of 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2-imino-4thiazolidinone (23.5 g) in 2 N HCl (200 ml) was refluxed for 6 hours. The solvent was evaporated off under reduced pressure, and the residue was neutralized with a saturated aqueous solution of sodium hydrogencarbonate. The crystals (23.5 g, 97.5%) which precipitated were collected by filtrationand recrystallized from DMF-H2O to give 5-{4-[2-(5-ethyl-2pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione as colorless needles (20.5 g, 86.9%), melting point 183°-184°C.In practice it is usually used as hydrochloride salt.

Therapeutic Function

Antidiabetic

InChI:InChI=1/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

• 105355-26-8 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2-imino-4-thiazolidinone 
• 144809-28-9 5-{4-[2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione 
• 646519-88-2 5-{4-[2-chloro-2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-2,4-thiazolidene dione 
• 646519-89-3 5-{4-[2-chloro-2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-2,4-thiazolidene dione hydrochloride 
• 914249-67-5 pioglitazone imino ether 
• 136401-70-2 (E)-5-<4-<2-(5-Ethyl-2-pyridyl)ethoxy>benzylidene>-2,4-thiazolidinedione 
• 105355-25-7 methyl 2-bromo-3-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]phenyl}propionate 
• 17356-08-0 thiourea 
• 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 
• 90643-32-6 2-(5-ethyl-1-oxypyridin-2-yl)ethanol 
• 646519-82-6 5-ethyl-2-[2-oxo-(1,3,2)dioxathiolan-4-yl]pyridine 

Downstream Products

• 1235470-90-2 3-(2-biphenyl-4-yl-2-oxo-ethyl)-5-{4-[2-(5-ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione 
• 959687-65-1 (R)-5-({p-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione 
• 1263978-84-2 (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate 
• 1263978-86-4 (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione tosylate 
• 1207681-45-5 (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione hydrochloride 
• 1329116-02-0 (5R)-5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-1,3-thiazolidine-2,4-dione hydrobromide 
• 1450912-73-8 C₂₆H₃₁F₂N₅O₃S 

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ENANTIOMERIC RESOLUTION METHOD

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