- Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
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Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].
- Chaturvedi, Radha Nandan,Pendem, Krishnaiah,Patel, Vipul P.,Sharma, Mukta,Malhotra, Sunita
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p. 2069 - 2084
(2018/08/22)
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- Base Mediated Synthesis of Alkyl-aryl Ethers from the Reaction of Aliphatic Alcohols and Unsymmetric Diaryliodonium Salts
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The base mediated coupling of aliphatic alcohol pronucleophiles with unsymmetric diaryliodonium salt electrophiles is described. This metal-free reaction is operationally simple, proceeds at mild temperature, and displays broad substrate scope to generate industrially important alkyl-aryl ethers in moderate to excellent yield. The synthetic utility of these reactions is demonstrated, and aspects of sustainability are highlighted by the use of unsymmetric aryl(mesityl)iodonium arylating reagents.
- Sundalam, Sunil K.,Stuart, David R.
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p. 6456 - 6466
(2015/06/30)
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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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- Synthesis and in vitro antimicrobial screening of new azetidin-2-ones of 5-ethyl pyridine-2-ethanol
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A new series of azetidinones is described in this paper; Schiff base (4a-o) were synthesized from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde, which was used to synthesize azetidinones (5a-o), (6a-o), and (7a-o). The structures of the synthesized compou
- Patel, Navin B.,Patel, Hemant R.,Shaikh, Faiyazalam M.,Rajani, Dhanji
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p. 775 - 787
(2014/06/10)
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- Design and synthesis of new imidazolinone derivatives as potential antifungal agents
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A new series of chalcones, pyrimidines, and imidazolinone is described; chalcones (4a-o) were prepared from the lead 4-[2-(5-ethylpyridin-2-yl)ethoxy] benzaldehyde. Pyrimidines (5a-o) were prepared from the reaction of chalcones and guanidine nitrate in a
- Patel, Navin B.,Patel, Hemant R.
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scheme or table
p. 373 - 380
(2011/05/14)
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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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- 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 6
(2009/01/20)
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- Synthesis and?antimicrobial studies of?a?new series of?2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles
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A series of novel 2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles were synthesized by the oxidative cyclisation of hydrazones derived from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde and aroylhydrazines using chloramine-T as oxidant. IR, NMR and elemental analysis characterized the newly synthesized compounds. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Out of the compounds studied, compounds 8c and 8d showed significant inhibition. Compounds 8b, 8f, 8k and 8e showed moderate activity. The minimum inhibitory concentration of the compounds was in the range of 8-26 μg ml-1 against bacteria and 8-24 μg ml-1 against fungi. The title compounds represent a novel class of potent antimicrobial agents.
- Gaonkar,Rai,Prabhuswamy
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p. 841 - 846
(2007/10/03)
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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 16
(2008/06/13)
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- PROCESS FOR THE SYNTHESIS OF PIOGLITAZONE HYDROGEN CHLORIDE
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The invention relates to a process for the synthesis of pioglitazone hydrogen chloride - which is an antidiabetic drug - via novel intermediates by reacting 4-[2-(5-ethyl-2-pyridinyl)-ethoxy]-benzaldehyde salt of formula (II), wherein HX is: HCI, CF3COOH, C4H4O4, (COOH)2 with a base and then thiazolidine-2,4-dione, and the obtained 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methylene]-2,4-thiazolidinedione base is treated with hydrochloric acid and the obtained 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl] methylene]-2,4-tiazolidinedione hydrogen chloride of formula(III) is hydrogenated in the presence of a catalyst. Further objects of the invention are the salts of general formula (II) and the benzylidene derivative of formula (III).
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Page/Page column 11-12
(2008/06/13)
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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 17-18
(2008/06/13)
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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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- 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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- 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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- 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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