- NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES
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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.
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- 5-DEUTERO-2,4-THIAZOLIDINEDIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
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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.
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Paragraph 0368; 0369
(2014/09/30)
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- A NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES.
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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.
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- Process development and scale-up of the potential thiazolidinedione antidiabetic candidate PNU-91325
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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.
- Carpenter, Donald E.,Imbordino, Rick J.,Maloney, Mark T.,Moeslein, Jeffery A.,Reeder, Michael R.,Scott, Allen
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p. 721 - 728
(2013/09/06)
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- Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone
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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).
- Tanis, Steven P.,Parker, Timothy T.,Colca, Jerry R.,Fisher, Roberta M.,Kletzein, Rolf F.
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p. 5053 - 5063
(2007/10/03)
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- Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones
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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.
- Sohda,Momose,Meguro,Kawamatsu,Sugiyama,Ikeda
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- 2,4-thiazolidinediones
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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.
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