- Robust Acenaphthoimidazolylidene Palladacycles: Highly Efficient Catalysts for the Amination of N-Heteroaryl Chlorides
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A series of robust N-heterocyclic carbene palladacycles have been successfully developed. These showed high catalytic activity and selectivity toward the challenging amination of N-heteroaryl chlorides. Different primary and secondary amines were fully compatible with this catalytic system. Remarkably, no double amination products could be detected when primary amines were utilized in our catalytic transformation. Furthermore, the protocol has been successfully extended to synthesize rosiglitazone, a clinical drug for diabetes mellitus, highlighting its potential pharmaceutical feasibility.
- Deng, Qinyue,Zhang, Yang,Zhu, Haibo,Tu, Tao
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supporting information
p. 2364 - 2368
(2017/09/06)
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- Synthetic optimization of rosiglitazone and related intermediates for industrial purposes
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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.
- Meng, Ge,Zheng, Meilin,Dong, Mengshu,Gao, Yang,Zheng, Aqun,Li, Zhenyu,Hu, Ruizhi
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p. 2023 - 2033
(2016/03/16)
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- An alternative synthetic route for an antidiabetic drug, rosiglitazone
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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.
- Jawale, Dhanaji V.,Pratap, Umesh R.,Mane, Ramrao A.
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scheme or table
p. 924 - 928
(2012/03/26)
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- Microwave-assisted synthesis of the antihyperglycemic drug rosiglitazone
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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.
- Gaonkar, Santosh L.,Shimizu, Hiroki
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experimental part
p. 3314 - 3317
(2010/06/21)
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- A PROCESS FOR THE PREPARATION OF SUBSTITUTED PHENYL ETHER COMPOUNDS AND ROSIGLITAZONE
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A novel process for the preparation of a compound of the formula (II), which is useful as intermediate compound for the preparation of thiazolidinedione derivatives, such as rosiglitazone, pioglitazone, troglitazone and ciglitazone, is disclosed. The novel process comprising reacting a compound of the formula (III) with a compound of the formula (IV) in a mixture of a non-polar water immiscible organic solvent and water (two phase system) with an alkali metal hydroxide or an alkali metal carbonate as a base in the presence of a phase transfer catalyst. In the first aspect of the present invention comprising reacting 2-(N-methyl-N-(2- pyridyl) ethanol with 4-fluorobenzaldehyde in the mixture of a non-polar water immiscible organic solvent, preferably toluene, and water with an alkali metal hydroxide or an alkali metal carbonate as a base, preferably potassium hydroxide, in the presence of a phase transfer catalyst, e.g. tetra n-butylammonium hydrogensulphate or benzyltriethylammonium chloride, to obtain 4-[2-(N-methyl-N-(2- pyridyl)amino)ethoxy]benzaldehyde, which is the key intermediate for preparing rosiglitazone and its salts, e.g. maleate salt or phosphate salt, useful in the treatment of Type II diabetes.
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Page/Page column 10; 13
(2008/06/13)
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- SMALL MOLECULE BCL-XL/BCL-2 BINDING INHIBITORS
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Bcl-xL/Bcl-2 binding inhibitors useful in the treatment of unwanted proliferating cells, including cancers and precancers, in subjects in need of such treatment. Also provided are methods of treating a subject having unwanted proliferating cells comprising administering a therapeutically effective amount of a Bcl-xL/Bcl-2 binding inhibitor described herein to a subject in need of such treatment. Also provided are methods of preventing the proliferation of unwanted proliferating cells, such as cancers and precancers, in a subject comprising the step of administering a therapeutically effective amount of Bcl-xL/Bcl-2 binding inhibitor described herein to a subject at risk of developing a condition characterized by unwanted proliferating cells.
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Page/Page column 30
(2008/06/13)
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- Polymer-assisted solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia).
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The commercially important antihyperglycemic agent Rosiglitazone 1(Avandia) has been prepared in high purity by a multi-step, polymer-assisted solution phase (PASP) synthesis without the need for the conventional chromatographic purification of any intermediates.
- Li, Xin,Abell, Chris,Warrington, Brian H,Ladlow, Mark
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p. 4392 - 4395
(2007/10/03)
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- benzyl>-2,4-thiazolidinediones as Potent Antihyperglycemic Agents
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A series of -2,4-thiazolidinediones and benzyl>-2,4-thiazolidinediones was synthesized from the corresponding aldehydes.Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045).The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies.Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 BI/6 ob/ob mice.From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.
- Cantello, Barrie C.C.,Cawthorne, Michael A.,Cottam, Graham P.,Duff, Peter T.,Haigh, David,et al.
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p. 3977 - 3985
(2007/10/02)
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- Facile Biocatalytic Reduction of the Carbon-Carbon Double Bond of 5-Benzylidenethiazolidine-2,4-diones. Synthesis of (+/-)-5-(4-ethoxy>benzyl)thiazolidine-2,4-dione (BRL 49653), its (R)-(+)-Enantiomer and Analogues
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A novel biotransformation system for the reduction of carbon-carbon double bonds in 5-benzylidenethiazolidine-2,4-diones, to give the corresponding 5-benzylthiazolidine-2,4-diones, using whole cells of red yeasts is described.These reduced compounds, which are recovered in good yield, are of potential use in the treatment of non-insulin dependent diabetes mellitus.The mild reaction conditions developed allow reduction of 5-benzylidenethiazolidine-2,4-diones containing other functionalities which are not compatible with alternative reduction methods.The biocatalytic reduction is enantioselective and the synthesis of R-(+)-5-(4-ethoxy>benzyl)thiazolidine-2,4-dione by Rhodotorula rubra CBS 6469 and structure confirmation by X-ray crystallography is detailed.Optimisation of reaction conditions (including immobilisation) for these whole cell reduction systems is described.
- Cantello, Barrie C. C.,Eggleston, Drake S.,Haigh, David,Haltiwanger, R. Curtis,Heath, Catherine M.,et al.
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p. 3319 - 3324
(2007/10/02)
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- Compounds
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Compounds of formula (I): STR1 or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.
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- Compounds
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Compounds of formula (I): STR1 or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.
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