111025-46-8 Usage
Description
Pioglitazone, also known as Actos, is an odorless, white, crystalline powder belonging to the class of thiazolidinediones. It is a selective agonist of the peroxisome proliferator-activated receptor γ (PPARγ) and exhibits hypoglycemic activity. Pioglitazone must be converted to a salt, such as its hydrochloride, to have water solubility. Pioglitazone is used as a racemic mixture due to the in vivo interconversion of its two enantiomers, which results in no differences in their pharmacological activity.
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
Check Digit Verification of cas no
The CAS Registry Mumber 111025-46-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,1,0,2 and 5 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 111025-46:
(8*1)+(7*1)+(6*1)+(5*0)+(4*2)+(3*5)+(2*4)+(1*6)=58
58 % 10 = 8
So 111025-46-8 is a valid CAS Registry Number.
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
111025-46-8Relevant articles and documents
Radical Hydroarylation of Functionalized Olefins and Mechanistic Investigation of Photocatalytic Pyridyl Radical Reactions
Seath, Ciaran P.,Vogt, David B.,Xu, Zihao,Boyington, Allyson J.,Jui, Nathan T.
supporting information, p. 15525 - 15534 (2018/11/23)
We report the photoredox alkylation of halopyridines using functionalized alkene and alkyne building blocks. Selective single-electron reduction of the halogenated pyridines provides the corresponding heteroaryl radicals, which undergo anti-Markovnikov addition to the alkene substrates. The system is shown to be mild and tolerant of a variety of alkene and alkyne subtypes. A combination of computational and experimental studies support a mechanism involving proton-coupled electron transfer followed by medium-dependent alkene addition and rapid hydrogen atom transfer mediated by a polarity-reversal catalyst.
NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES
-
, (2014/04/03)
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.
Practical synthesis of pioglitazone: Ligand substitution reaction with oxido vanadium(IV) and biological activity
Altun, Oezlen,Kuecuektepe, Caner,Yoeruek, Ozan,Feyizoglu, Adilhan
, p. 221 - 225 (2013/04/10)
The authors performed two types of experiments: the reduction of 5-{4-[2-(5-ethyl-2-pyridyl)etoxy]benzilidine}-2-4-thiazolidinedione to pioglitazone (5-{4-[2-(5-ethyl-2-pyridyl) etoxy]benzil}-2-4-thiazolidinedione) with magnesium/methanol and the synthesis of an oxidovanadium(IV) complex of pioglitazone in methanol under refluxing conditions. The structures of pioglitazone and its oxidovanadium(IV) complex were analyzed by using physicochemical and spectroscopic techniques. Comparisons of the spectral measurements of pioglitazone with those of its oxidovanadium(IV) ion complex are useful in determining the atoms of the ligand that are coordinated to the metal ion. In addition, antibacterial and antifungal activities of the complex were studied and the complex is screened against bacteria and fungi.
