- Practical synthesis of pioglitazone: Ligand substitution reaction with oxido vanadium(IV) and biological activity
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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.
- Altun, Oezlen,Kuecuektepe, Caner,Yoeruek, Ozan,Feyizoglu, Adilhan
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Read Online
- Hydrogenation of 5-alkylidene-2,4-thiazolidiones on Pd/C catalysts under mild conditions: An alternative synthesis route to pioglitazone
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The hydrogenation of 5-alkylidene-2,4-thiazolidiones was studied using Pd/C to establish an alternative process for pioglitazone synthesis. The reportedly sluggish reactivity was due to the high reaction temperature in formic acid. The conditions were improved to 1 atm at 296 K, which results in a quantitative product with a smaller amount of the catalyst. Graphical Abstract: [Figure not available: see fulltext.]
- Sugimura, Takashi,Oie, Kanae,Misaki, Tomonori,Okamoto, Yasuaki,Tanaka, Kenji,Mori, Hiroyuki
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Read Online
- Recoverable, Reusable, Highly Active, and Sulfur-Tolerant Polymer Incarcerated Palladium for Hydrogenation
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A new type of immobilized palladium, PI (polymer incarcerated) Pd (2b), from Pd(PPh3)4 and copolymer (1b) has been developed. The excellent activity of PI Pd has been demonstrated in hydrogenation of various olefins, benzyl ethers, and nitro and aromatic compounds. PI Pd is tolerant under high pressure and high temperature and can be recovered and reused several times without loss of activity even under harsh conditions. Moreover, PI Pd is highly resistant to poisoning by sulfur.
- Okamoto, Kuniaki,Akiyama, Ryo,Kobayashi, Shu
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Read Online
- Radical Hydroarylation of Functionalized Olefins and Mechanistic Investigation of Photocatalytic Pyridyl Radical Reactions
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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.
- Seath, Ciaran P.,Vogt, David B.,Xu, Zihao,Boyington, Allyson J.,Jui, Nathan T.
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supporting information
p. 15525 - 15534
(2018/11/23)
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- Phosphoryl chloride mediated synthesis of 5-arylidene-2,4- thiazolidinediones derivatives via aromatic bisulfite adducts
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The carbon-carbon bond formation by the condensation of bisulfite adduct of aromatic aldehydes with thiazolidine-2, 4-dione to furnish 5-arylidene-2,4- thiazolidinedione's has been investigated. This novel methodology was applied to convert substituted aryl bisulfite adducts to corresponding 5-arylidene-2,4-thiazolidinedione's with POCl3 in less-polar solvents such as toluene, chlorobenzene and o-xylene. 5-(4-methoxybenzylidene) thiazolidine-2,4-dione and 5-(4-ethoxybenzylidene)thiazolidine-2,4-dione were obtained in good yields.
- Mohanty, Sandeep,Reddy. G, Sandeep,Karmakar, Arun Chandra
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p. 197 - 202
(2014/05/20)
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- 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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- Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation
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The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.
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- PHARMACEUTICAL COMPOSITIONS CONTAINING A BIGUANIDE AND A THIAZOLIDINEDIONE
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The present invention relates to pharmaceutical compositions that include a combination of a biguanide present in an extended-release form and a thiazolidinedione present in an immediate-release form. The present invention further relates to the processes for preparing such compositions.
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- An improved process for pioglitazone and its pharmaceutically acceptable salt
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An improved process for pioglitazone (1) is described. The process features high-yielding transformations employing inexpensive reagents and recoverable solvents.
- Madivada, Lokeswara Rao,Anumala, Raghupathi Reddy,Gilla, Goverdhan,Alla, Sampath,Charagondla, Kavitha,Kagga, Mukkanti,Bhattacharya, Apurba,Bandichhor, Rakeshwar
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scheme or table
p. 1190 - 1194
(2010/04/22)
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- 5-(4-HYDROXYBENZYL)THIAZOLIDINE-2,4-DIONE AS INTERMEDIATE FOR SYNTHESIS OF THIAZOLIDINEDIONE BASED COMPOUNDS AND PROCESS FOR PREPARING THE SAME
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The present invention relates to 5-(4-hydroxybenzyl)thiazolidine-2,4-dione represented by the following Chemical Formula [1], which is useful as an intermediate for synthesis of thiazolidinedione based compounds, a method for preparing the compound, and a method for preparing pioglitazone or pioglitazone hydrochloride, which is a thiazolidinedione based drug and useful in treating and preventing diabetes, using the 5-(4-hydroxybenzyl)thiazolidine-2,4-dione represented by Chemical Formula [1] as an intermediate:
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Page/Page column 9; 15; 21-22; 27
(2009/12/28)
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- A METHOD FOR PREPARATION OF THIAZOLIDINEDIONE DERIVATIVES
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The present invention offers the conjugate reduction of α-β-unsaturated thiazolidinedione derivatives which involves the reagents cobalt ion in the form of cobaltous chloride hexahydrate, the ligand dimethyl glyoxime in N, N dimethyl formamide, the reducing agent sodium borohydride and the solvent media for the reaction is polyethylene glycol (PEG).
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Page/Page column 7-8
(2009/10/18)
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- A PROCESS FOR THE PREPARATION OF 4-[2-(5-ETHYL-2-PYRIDYL)ETHOXY]NITROBENZENE AND PIOGLITAZONE
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A process for the preparation of 4-[2-(5-ethyl-2-pyridyi)ethoxy]nitrobenzene is described, which comprises the step of reacting 2-(5-ethyl-2-pyridyl)ethanol with 1-fluoro-4-nitrobenzene in acetone in the presence of an alkali metal hydroxide. The intermediate 4-[2-(5-ethyl-2-pyridyI)ethoxy]nitrobenzene is used for the preparation of pioglitazone.
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Page/Page column 7
(2009/12/05)
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- NOVEL PROCESS FOR THE SYNTHESIS OF PIOGLITAZONE AND ITS SALTS THEREOF
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Present invention relates to an improved process for the preparation of thiazolidinedione derivatives. Further the invention provides the hydrogenation of acid addition salt of benzylidene compound with less reducing agent under low Hydrogen gas pressure to get substantially pure thiazolidinedione derivatives with improved yields.
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Page/Page column 7
(2009/01/20)
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- Pioglitazone impurities
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Methods of preparation of API pioglitazone were discussed from the point of view of impurities occurrence. Four real impurities (I-IV) of pioglitazone were prepared and characterized by means of NMR spectroscopy.
- Richter, Jindrich,Jirman,Havlicek,Hrdina
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p. 580 - 584
(2008/09/19)
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- PROCESSES FOR THE PREPARATION OF PIOGLITAZONE OR SALTS THEREOF
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The present invention provides processes for the preparation of highly pure pioglitazone or a salt thereof. In addition, the present invention provides pioglitazone or a salt thereof having about 0.1% or less of dehydropioglitazone impurity.
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Page/Page column 10 - 15
(2008/06/13)
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- Stabilized pharmaceutical composition comprising antidiabetic agent
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This invention discloses a stabilized pharmaceutical composition comprising an antidiabetic agent and a stabilizer. The preferred stabilizers are selected from the group consisting of ascorbic acid, malic acid, maleic acid, tartaric acid, furmaric acid, citric acid, or combinations thereof. The antidiabetic agent is selected from the group consisting of [(±)5-[[2-(5-ethyl-2-pyridinyl)ethoxyl]phenyl]methyl]-thiazolidine-2,4-dione and (±)5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione. This invention also discloses amorphous forms of said antidiabetic agents and a process of preparation thereof, and a method for medical treatment of diabetic mellitus using said pharmaceutical composition.
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Page/Page column 12
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PRODUCTION OF DERIVATIVES OF THIOZOLIDINEDIONES AND THEIR PRECURSORS
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The invention provides a process for preparing derivatives of thiozolidinediones and their precursors comprising, (a) reacting a compound of general formula I wherein R1, R2 and R3 may be same or different and represent H, alkyl or alkoxy with C varying from 1 to 6, halogens, mono or di-substituted alkyl and aryl amines, and M represents hydrogen (H) or alkali metal selected from Na, K or Li with a compound of formula II, wherein R4 has the same meaning as R1 or R2 or R3 and X is halogen in presence or absence of solvent(s) under effective conditions to produce nitro ethers of general formula III, where in R1 to R4 has the same meaning as given above, provided when M is H and not its alkali metal salt, an alkali metal salt such as hydroxide or carbonate is required to be added while conducting the said reaction, (b) subjecting the said nitro ethers, with or without isolation, to Raney nickel-catalyzed reduction under conditions effective to produce corresponding nitro aniline ethers (c) coupling the said aniline ether with acrylates under Meerwein arylation conditions in presence of hydrobromic acid to produce α bromo substituted carboxylic acid derivatives followed by subjecting to solvent extractive purification (d) cyclising the purified derivative of α bromo substituted carboxylic acid as obtained in step (c) with thiourea to yield 2-imino -4-thiazolidinones then (e) hydrolyzing the said 2-imino-4-thiazolidinones to produce 2, 4-thiazolidinones and converting the same to its hydrochloride salts as white crystalline solids known to exhibit antidiabetic activity, by conventional methods.
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Page/Page column 26; 27
(2010/10/20)
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- INTERMEDIATE COMPOUND WHICH IS USED FOR THE PREPARATION OF PIOGLITAZONE
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The present invention relates to a novel compound of formula (IV) which is an intermediate that can be used for the preparation of pioglitazone. It also relates to a method of obtaining the novel compound (IV) starting from the natural product L-tyrosine, in which the amino group is protected in the form of aromatic imino group, and a method of obtaining pioglitazone from the said intermediate.
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- PROCESS FOR PREPARING THIAZOLIDINEDIONES
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This invention provides a process for reducing an exocyclic double bond at the 5-position of a thiazolidinedione moiety of a thiazolidinedione precursor comprising the steps of: a) preparing a solution or suspension of the thiazolidinedione precursor in a non-ether solvent medium with a base, and b) combining the solution or suspension with a dithionite source. Preferred solvent media include aqueous N,N-dimethylformamide. Sodium dithionite is a preferred dithionite source. In particular the application discloses preparation processes for Pioglitazone, Rosilitazone and Troglitazone.
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Page/Page column 12
(2008/06/13)
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- USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula
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- Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
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A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative is herein disclosed and described.
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- Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
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A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative and a disintegrating agent is herein disclosed and described. The dosage formulation exhibits a significant increase in bioavailability of the thiazolidinedione derivative component compared to conventional immediate release dosage forms containing only a thiazolidinedione derivative.
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- A PROCESS FOR PURIFICATION
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The present invention provides a process for purification of pharmaceutically active compounds selected from the group consisting of thiazolidinedione derivatives and trans-3-Ethyl-2,5-dihydro-4-methyl-N- [2-[4-[[[[(4-methylcyclohexyl)amino] carbonyl] amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide comprising extraction in a solvent comprising an alkanol (C1-C4) and ammonia.
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Page/Page column 11-12
(2010/02/12)
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- PROCESSES FOR MAKING PIOGLITAZONE AND COMPOUNDS OF THE PROCESSES
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Pioglitazone can be made via a Darzens Condensation reaction in an industrially useful process.
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Page/Page column 18-20; 20-21
(2008/06/13)
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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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- Agent for improving ketosis
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An agent for improving ketosis which comprises an insulin sensitizer, which has an excellent action and low toxicity.
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- Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
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A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative is herein disclosed and described.
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- PROCESSES FOR MAKING THIAZOLIDINEDIONE DERIVATIVES AND COMPOUNDS THEREOF
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A compound of the formula (I): wherein A represents a ring group connected to the oxygen atom by a C1 to C6 hydrocarbon chain, R is hydrogen or a C1-C4 alkyl, and Q is hydrogen, or an amine protecting group such as acetyl, trifluoroacetyl, benzoyl, benzyl, or trityl, is useful in making thiazolidinedione derivatives (formula (II)), such as pioglitazone, rosiglitazone and troglitazone.
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- Method for preparing compounds derived from thiazolidinedione, oxazolidinedione or hydantoin
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A method for preparing a thiazolidinedione, oxazolidinedione or hydantoin compound of formula (I) from a compound of formula (II): wherein Q represents an oxygen atom or a sulfur atom; Q1 represents an oxygen atom or a sulfur atom; R1 and R2, which can be identical or different, represent a hydrogen atom, a C1-10 alkyl chain, a cycloalkyl, an alkylaryl, an arylalkyl; the alkyl, cycloalkyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH2, NHR3, N(R3)2, wherein R3 represents an alkyl, an alkoxy or an alkylcarbonyl, reacting a compound of formula (II) with formic acid, either as a hydrogen donor in a hydrogen-transfer reaction or as a solvent in a hydrogenation reaction, in the presence of a catalyst containing a transition metal to obtain a corresponding compound of formula (I).
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- Thiazolidinedione, oxazolidinecarboxylic Pyrimidinedione preparation of compound derived
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A method for preparing a thiazolidinedione, oxazolidinedione or hydantoin compound of formula (I) from a compound of formula (II):wherein Q represents an oxygen atom or a sulfur atom; Q1 represents an oxygen atom or a sulfur atom; R1 and R2, which can be identical or different, represent a hydrogen atom, a C1-10 alkyl chain, a cycloalkyl, an alkylaryl, an arylalkyl; the alkyl, cycloalkyl, alkylaryl or arylalkyl groups being optionally substituted by an alkyl, an alkoxy or aryloxy, a halogen, a hydroxy, a sulfino, a sulfonyl, an amino such as NH2, NHR3, N(R3)2, wherein R3 represents an alkyl, an alkoxy or an alkylcarbonyl, reacting a compound of formula (II) with formic acid, either as a hydrogen donor in a hydrogen-transfer reaction or as a solvent in a hydrogenation reaction, in the presence of a catalyst containing a transition metal to obtain a corresponding compound of formula (I).
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- PROCESS FOR THE PREPARATION OF 5-[[4-[2-(5-ETHYL-2-PYRIDINYL)ETHOXY]PHENYL] METHYL]-2,4-THIAZOLIDINEDIONE
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A process for the preparation of 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (formula 1) comprising a. reacting diazonium salt of 4-[2-(5-Ethyl-2-pyridyl) ethoxy] amino- benzene, compound of formula 2, with acrylamide, aqueous HX (wherein X is Br or Cl), under meerwein arylation conditions to yield compound of formula 3; b. condensing compound of formula 3 with thiourea to obtain compound of formula 4; and c. converting compound of formula 4 to compound of formula 1.
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- A PROCESS FOR THE PRODUCTION OF SUBSTITUTED PHENYL ETHERS
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The present invention provides a process to prepare substituted phenyl ethers. More particularly the present invention provides a process to produce a compound represented by the Formula I: wherein H1 is a substituted pyridyl group and R1 can be an aldehyde, cyano or nitro group.The compound I is a key intermediate in the preparation of pharmaceutically useful thiazolidinedione derivatives such as pioglitazone, rosiglitazone, etc.
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- Drug comprising combination
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A TNF-α inhibitor comprising an insulin sensitizer in combination with an HMG-CoA reductase inhibitor is useful as an agent for the prophylaxis or treatment of an inflammatory disease and the like.
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- Neovascularization inhibitors
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An angiogenesis inhibitor containing a compound represented by the formula wherein R4 is an optionally substituted hydrocarbon group and the like; Xa is a bond and the like; k is an integer of 1 to 3; Ya is an oxygen atom and the like; ring Ea is a benzene ring optionally having additional substituent(s); p is an integer of 1 to 8; R5 is a hydrogen atom and the like; q is an integer of 0 to 6; r is 0 or 1; R8 is a hydroxy group and the like; and R6 and R7 are hydrogen atoms and the like, or a salt thereof is useful as an agent for the prophylaxis or treatment of tumor and the like.
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- Combinations comprising dipeptidylpeptidase-iv inhibitor
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The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, α-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and α2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.
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- Use of thiazolidinedione derivatives in the treatment of insulin resistance
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The present invention provides methods of using thiazolidinedione in the treatment of insulin resistance.
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- Method for preventing and for treating autoimmune disease
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A method for preventing or treating autoimmune diseases (excluding type I diabetes) by administering an insulin resistance improving substance as an active ingredient.
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- Production of benzaldehyde compounds
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A method of producing a compound represented by the formula: STR1 wherein R1 stands for hydrogen or an optionally substituted alkyl or acyl group, which comprises reacting a compound represented by the formula: STR2 wherein R1 is of the same meaning as defined above, and R2 stands for an optionally halolgenated alkyl group or an optionally substituted phenyl group with a compound represented by the formula: STR3 in a lower alcohol in the presence of an alkali metal or alkaline earth metal carbonate; the compound (III) being useful as starting compounds for producing thiazolidinedione derivatives having hypoglycemic and hypolipidemic activities.
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- Method for producing ethers
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A compound of the formula: [wherein A stands for an aromatic ring residue, a group shown by R1 --CO-- (wherein R1 stands for an aliphatic hydrocarbon residue, aromatic hydrocarbon residue, a heterocyclic residue, an aromatic alipahtic hydrocarbon residue or an alicyclic hydrocarbon residue) or R2 --CH=CH-- (wherein R2 stands for an aliphatic hydrocarbon residue an aromatic hydrocarbon residue a heterocyclic residue an aromatic aliphatic hydrocarbon residue or an alicyclic hydrocarbon residue), and B stands for an aromatic ring residue], can be obtained in high yield, at high purity level by short reaction time, by reacting a compound of the formula: (wherein A is of the same meaning as defined above, and X stands for a leaving group) with a compound represented by the general formula: (wherein M stands for an alkali metal atom or an alkaline earth metal atom and B is of the same meaning as defined above) in a non-aqueous solvent.
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- Pyridine N-oxide compounds which are useful as hypoglycemic and hypolipidemic agents
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There is disclosed a novel thiazolidinedione derivative of the general formula (I): STR1 wherein R1 and R2 are the same or different and are a hydrogen atom or a lower alkyl group, or a salt thereof. The thiazolidinedione derivative has hypoglycemic activity and hypolipidemic activity.
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- Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds
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Various analogues of a new antidiabetic agent, pioglitazone (AD-4833, U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4-thiazolidinediones (I), this-analogues of pioglitazone, were prepared via Meerwein arylation of the alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene)-2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKA(y)) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4-thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and the benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed.
- Momose,Meguro,Ikeda,Hatanaka,Oi,Sohda
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p. 1440 - 1445
(2007/10/02)
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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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- Method for producing thiazolidinedione derivatives
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A compound of the formula: STR1 (wherein R1 is hydrogen or a lower alkyl) can be produced advantageously by (1) reacting a compound of the formula: STR2 (wherein R1 has a meaning given above) with a halogenating agent or sulfonyl halide to give a compound of the formula: STR3 (wherein R1 has a meaning given above and X is a halogen or an alkyl- or aryl-sulfonyloxy), (2) reacting the resulting compound with a compound of the formula: STR4 to give a compound of the formula: (wherein R1 has the meaning given above), (3) reacting the resulting compound with a compound of the formula: STR5 to give a compound of the formula: STR6 (wherein R1 has the meaning given above), and (4) subjecting the resulting compound to catalytic reduction.
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- Thiazolidinedione derivatives, useful as antidiabetic agents
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Thiazolidinedione derivatives of the formula: STR1 and pharmacologically acceptable salts thereof are novel compounds, which exhibit in mammals blood sugar- and lipid-lowering activity, and are of value as a therapeutic agent for treatment of diabetes and hyperlipemia.
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