- Microbiological N-deoxygenation and C-oxygenation of pioglitazone-N-oxide in a single fermentation
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Oxygenation of pioglitazone-N-oxide by a microorganism isolated from soil was accompanied by N-deoxygenation to produce the pioglitazone metabolites 5-[4-[2-[5-(1-hydroxyethyl)-2-pyridyl]ethoxy]benzyl]-2,4-thiazolidinedione and 5-[4-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione. The oxygenating/deoxygenating organism has been characterized as Streptomyces hygroscopicus strain 02179 (UC 11099). The culture has been deposited with Agricultural Research Service, USDA, with accession number NRRL 18975.
- Johnson, Roy A.,Marshall, Vincent P.,Li, Grace P.,Sih, John C.,Cialdella, Joyce I.,Liggett, Walter F.,Nidy, Eldon G.
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Read Online
- Pioglitazone impurity preparation method
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The present invention relates to a pioglitazone impurity preparation method, wherein pioglitazone is placed in an organic solvent under the effect of an oxidizing reagent to obtain a pioglitazone oxide. According to the present invention, the method has advantages of mild impurity synthesis reaction condition, simple process, short reaction time, less by-product, good yield, and high product purity.
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Paragraph 0015-0023
(2017/04/29)
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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 0366; 0367
(2014/09/30)
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- Identification, isolation and characterization of potential degradation products in pioglitazone hydrochloride drug substance
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During stress degradation studies of pioglitazone hydrochloride, one major unknown oxidative degradation impurity and two major unknown base degradation impurities were identified by LC-MS. These impurities were isolated using preparative liquid chromatography. Based on the spectral data (1H NMR, 13C NMR, MS and IR), oxidative degradation impurity, base degradation impurity-1 and base degradation impurity-2 were characterized as pioglitazone N-oxide, 3-(4-(2-(5-ethylpyridine-2yl) ethoxy) phenyl)-2- mercaptopropanoic acid and 2-(1-carboxy-2-{4-[2-(5-ethylpyridine-2yl)-ethoxy] phenyl}-ethyl disulfanyl)-3-{4-[2-(5-ethylpyridine-2yl)-ethoxy] phenyl propanoicacid, respectively. The formation and mechanism of these impurities were discussed and presented.
- Ramulu,Thilak Kumar,Radha Krishna,Vasudev,Kaviraj,Rao,Someswara Rao
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experimental part
p. 162 - 168
(2011/08/05)
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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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