122321-04-4Relevant articles and documents
Preparation method of rosiglitazone
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Paragraph 0039-0041; 0047-0049; 0053-0055; 0059-0061; 0065, (2020/12/29)
The invention provides a preparation method of rosiglitazone. The preparation method is characterized by comprising the following steps: reacting 2-chloropyridine with 2-methylaminoethanol under the catalysis of sodium triphenylmethyl to generate 2-[N-methyl-N-(2-pyridine) amino] ethanol; then carrying out Williamson synthesis reaction on the 2-[N-methyl-N-(2-pyridine) amino] ethanol and 4-fluorobenzaldehyde under the catalysis of bis (trimethylsilyl) amino potassium to obtain 4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzaldehyde; then carrying out condensation reaction with thiazoline-2,4-diketone to obtain 5-{4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzylidene} thiazoline-2, 4-diketone; and carrying out reduction reaction under the catalysis of an organic manganese reagent to obtain the rosiglitazone. The preparation method is simple, mild in condition, high in reaction yield and suitable for industrial production.
Synthesis of Novel Thiazolidin-4-ones and Thiazinan-4-ones Analogous to Rosiglitazone
das Neves, Adriana M.,Campos, José C.,Gouvêa, Daniela P.,Berwaldt, Gabriele A.,Goulart, Taís B.,Avila, Cinara T.,Machado, Pablo,Zimmer, Geórgia C.,Cunico, Wilson
, p. 251 - 259 (2018/12/05)
This work reports the synthesis of thiazolidin-4-ones and thiazinan-4-ones analogous to rosiglitazone, a potent antidiabetic drug. The desired compounds were synthesized with moderate to good yields by one-pot reactions between different primary amines, mercaptoacetic or mercaptopropionic acids, and the 4-(2-(methyl(pyridin-2-yl)amino)ethoxy)benzaldehyde. The cyclocondensation reactions were carried out for 20?h, and all the products were characterized by 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, and one example by X-ray diffraction.
Synthetic optimization of rosiglitazone and related intermediates for industrial purposes
Meng, Ge,Zheng, Meilin,Dong, Mengshu,Gao, Yang,Zheng, Aqun,Li, Zhenyu,Hu, Ruizhi
, p. 2023 - 2033 (2016/03/16)
As an important newly Food and Drug Administration (FDA)-approved drug for treating diabetes, rosiglitazone (1) has received much attention from researchers in many areas. To search for an economical and convenient synthesis method for 1, we explored the reaction conditions and workup of a scalable five-step synthetic route by an orthogonal method to determine the best condition for each reaction step. The starting materials are commercially available, including 2-chloropyridine (2), N-methylethanolamine (3), 4-fluorobenzaldehyde (4a) or 4-hydroxybenzaldehyde (4b), and 1,3-thiazolidine-2,4-dione (5). The five sequential reaction steps are cyclization, alkylation, etherification, condensation, and reduction, having optimal yield of 90, 99, 59, 75, and 91 %, respectively. The best overall yield to synthesize rosiglitazone based on compound 2 was 40 %, being suitable for industrial purposes, using water as a green solvent and avoiding column chromatography during the last three reaction steps.
Facile aromatic nucleophilic substitution (SNAr) reactions in ionic liquids: An electrophile-nucleophile dual activation by [Omim]Br for the reaction
Zhang, Xiao,Lu, Guo-Ping,Cai, Chun
, p. 5580 - 5585 (2016/10/21)
A facile aromatic nucleophilic substitution (SNAr) reaction in recyclable [Omim]Br under relatively mild conditions has been described. An electrophile-nucleophile dual activation by [Omim]Br is also discovered based on control experiments, 1H NMR and IR spectroscopies. This chemistry provides an efficient and metal-free approach for the generation of Caryl-X (XS, N, O) bonds, many of which are significant synthetic intermediates or drugs, making this methodology attractive to both synthetic and medicinal chemistry.
Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I
Meng, Ge,Zheng, Meilin,Wang, Mei,Tong, Jing,Ge, Weijuan,Zhang, Jiehe,Zheng, Aqun,Li, Jingya,Gao, Lixin,Li, Jia
, p. 756 - 769 (2016/08/18)
A new series of 2-substituted imino-3-substituted-5- heteroarylidene-1,3-thiazolidine-4-ones as the potent bidentate PTP1B inhibitors were designed and synthesized in this paper. All of the new compounds were characterized and identified by spectra analysis. The biological screening test against PTP1B showed that some of these compounds have the positive inhibitory activity against PTP1B. The activity of the compounds with 5-substituted pyrrole on 5-postion of 1,3-thiazolidine-4-one are more potent than that of those compounds with 5-substituted pyridine group. Compound 14b, 14h and 14i showed IC50values of 8.66?μM, 6.83?μM and 6.09?μM against PTP1B, respectively. Docking analysis of these active compounds with PTP1B showed the possible interaction modes of these biheterocyclic compounds with the active sites of PTP1B. The inhibition tests against oncogenetic CDC25B were also conducted on this set of compounds to evaluate the selectivity and possible anti-neoplastic activity. Compound 14b also showed the lowest IC50of 1.66?μM against CDC25B among all the possible inhibitors, including 14g, 14h, 14i and 15c. Some pharmacological parameters including VolSurf, steric and electric descriptors of all the compounds were calculated to give some hints about the relative relationship with the biological activity. The result of this study might give some light on designing the possible anti-cancer drugs targeting at phosphatases. The most active compound 14i might be used as the lead compound for further structure modification of the new low molecular weight PTP1B inhibitors with the N-containing heterocyclic skeleton.
Synthesis and lipid-lowering evaluation of 3-methyl-1 H-purine-2,6-dione derivatives as potent and orally available anti-obesityagents
He, Linhong,Pei, Heying,Ma, Liang,Pu, Yuzhi,Chen, Jinying,Liu, Zhuowei,Ran, Yan,Lei, Lei,Fu, Suhong,Tang, Minghai,Peng, Aihua,Long, Chaofeng,Chen, Lijuan
supporting information, p. 595 - 610 (2014/12/11)
Obesity accompanied with metabolic disorder is often complicated with a strong link of dyslipidemia and insulin resistance, whose indicator is the excess accumulation of triglycerides (TG) in cells. Consideration the idea of lipid-lowering and improving insulin resistance, 34 novel compounds by combination the xanthine scaffold with the chain of Rosiglitazone have been synthesized. Among them, several compounds showed efficiency on reducing TG in 3T3-L1 adipoctyes, and 11c exhibited the most optimal capacity in lipid-lowering and improving obese clinical symptoms in DIO mice. Furthermore, the hydrochloride of 11c (11c·HCl) showed excellent bioavailability, 58.94%, over 2 folds than that (28.03%) of 11c, and the anti-obesity effect of 11c·HCl at 50 mg/kg dose was better than that of Metformin at 150 mg/kg dose in DIO mice, almost reversed HFD to a normal level. Thus, 11c·HCl might be a potent and orally available anti-obesity agent via alleviating the obese clinical symptoms, body fat, improving serum parameters and insulin resistance and TG clearance in liver.
Thiazolidin-4-one and thiazinan-4-one derivatives analogous to rosiglitazone as potential antihyperglycemic and antidyslipidemic agents
Raza, Saman,Srivastava, Swayam P.,Srivastava, Daya S.,Srivastava, Arvind K.,Haq,Katti
, p. 611 - 620 (2013/07/27)
A number of thiazolidin-4-one and thiazinan-4-one derivatives were prepared by three component condensation in one pot reaction method. These compounds were evaluated for anti-hyperglycemic activity by in vitro and in vivo assay systems. The compounds with thiazolidin-4-one and thiazinan-4-one moieties exhibited significant anti-hyperglycemic activity. A few compounds (3a, 3b, 4a and 4b) have exhibited both anti-hyperglycemic and anti-dyslipidemic activities. Among them the thiazinan-4-one derivative 4a showed maximal (45%) improvement in oral glucose tolerance test in db/db mice at 30 mg/kg oral dose.
An alternative synthetic route for an antidiabetic drug, rosiglitazone
Jawale, Dhanaji V.,Pratap, Umesh R.,Mane, Ramrao A.
experimental part, p. 924 - 928 (2012/03/26)
A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10 h.
Microwave-assisted synthesis of the antihyperglycemic drug rosiglitazone
Gaonkar, Santosh L.,Shimizu, Hiroki
experimental part, p. 3314 - 3317 (2010/06/21)
We developed a simple, rapid, high yielding, and environmentally benign microwave assisted total synthesis of rosiglitazone, an antihyperglycemic agent for diabetes mellitus Type II. We used microwave heating successfully to improve reactions in four of six steps and obtain quicker and higher yields. In addition, all intermediates were isolated in good yields with crystallizations only and did not require chromatographic separations.
Synthesis of 4-[2-(methyl-2-pyridin-2yl-amino)-ethoxy]-Benzaldehyde derivatives
Ravindranath,Rangaraju,Srikanth,Radhakrishana
experimental part, p. 47 - 52 (2011/06/21)
Several 2,4-thiazolidindiones were prepared from corresponding aryl aldehydes by Knovengel condensation between Aldehydes and 2,4-thiazolidindione which shows anti-hyperglycemic potency such as Pioglitazone and Rosiglitazone. In our attempt we have prepared 4-[2-(methyl-2-pyridin-2yl-amino)-ethoxy]- benzaldehyde derivatives. Condensation of aryl Aldehydes with aryl ketones by Aldol condensation and the derivatives may have comparable biological importance.
