- COMPOSITION COMPRISING HIGH PURITY PYRROLE DERIVATIVE AND METHOD FOR PREPARATION THEREOF
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The present invention relates to a composition comprising high purity pyrrole derivative and method for preparation thereof. The present invention particularly relates to compositions comprising Saroglitazar magnesium having purity of 99.0% or more, and one or more of an aldehyde compound of Formula (II), diketo oxirane compound of Formula (III), hydroxy methyl compound of Formula (IV) or dimer compound of Formula (V), relative to saroglitazar magnesium, each present in an amount of about 0.15% or less, respectively, by weight, when measured by area percentage of HPLC.
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Paragraph 0114-0115
(2022/02/05)
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- A highly efficient and enantioselective synthesis of EEHP and EMHP: intermediates of PPAR agonists
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Glycolate alkylation reactions of (S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one auxiliary has been optimised with high yields and diastereoselectivity on substituted benzyl and allyl bromides. The standardised reaction condition was employed for the stereoselective synthesis of EEHP and EMHP intermediates of PPAR agonists.
- Gangar, Mukesh,Harikrishnan,Goyal, Sandeep,Mungalpara, Maulik N.,Nair, Vipin A.
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p. 3462 - 3467
(2016/07/18)
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- PPAR-SPARING COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES
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The present invention relates to hydroxamate compounds and pharmaceutical compositions that are useful for treating and/or preventing metabolic inflammation mediated diseases such as diabetes, obesity, hypertension, dyslipidemia, a neurodegenerative disorder (e.g., Alzheimer's disease, Parkinson's disease, or Huntington's disease), or any combination thereof. Moreover, the present invention also provides methods of treatment for these diseases or disorders.
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Paragraph 0311-0312
(2015/02/19)
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- Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of α-Alkoxy-Substituted β-Ketoesters
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Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst RuII-(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99>). Additionally, after extensive screening of the reaction conditions, the use of RuII- and RhIII-tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn α-alkoxy-β-hydroxyesters with excellent enantiocontrol (up to 99‰ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)-propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type-II diabetes. RuII-catalyzed asymmetric transfer hydrogenation with dynamic kinetic resolution was successfully applied to a wide variety of racemic α-alkoxy-β-ketoesters derived from substituted aromatic and heteroaromatic benzaldehydes and cinnamaldehydes (see scheme; PMB=p-methoxybenzyl, S/C=substrate/catalyst ratio).
- Monnereau, Laure,Cartigny, Damien,Scalone, Michelangelo,Ayad, Tahar,Ratovelomanana-Vidal, Virginie
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p. 11799 - 11806
(2015/08/11)
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- A new enantioselective synthesis of (S)-2-ethoxy-3-(4-hydroxyphenyl) propanoic acid esters (EEHP and IEHP), useful pharmaceutical intermediates of PPAR agonists
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A new enantioselective synthetic route to the title compounds has been developed in a simple and practical way with high enantiopurity using commercially available starting material.
- Mujahid,Kunte,Muthukrishnan
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p. 3223 - 3226
(2014/06/09)
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- A PROCESS FOR THE PREPARATION OF 3-ARYL-2-HYDROXY PROPANOIC ACID COMPOUNDS
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The present disclosure provides a process for synthesis of 3-aryl-2-hydroxy propanoic acid derivatives of formula (S)-1. wherein R1 represents H or (C1-C5) alkyl groups and R2 represents (C1-C5) alkyl groups.
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- PPAR-SPARING THIAZOLIDINEDIONES AND COMBINATIONS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The present invention relates to PPARy- sparing compounds and pharmaceutical compositions formulated with such compounds that are useful for treating, delaying the onset of, or reducing the symptoms of a neurodegenerative disorder including Huntington's disease, epilepsy, AMS, and MS.
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Paragraph 0456; 0457
(2014/07/07)
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- A PROCESS FOR PREPARATION OF PYRROLES HAVING HYPOLIPIDEMIC HYPOCHOLESTEREMIC ACTIVITIES
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The present invention provides pyrroles having hypolipidemic hypocholesteremic activities. The invention provides saroglitazar and its pharmaceutically acceptable salts, hydrates, solvates, polymorphs or intermediates thereof. The invention also provides a process for the preparation of saroglitazar. The invention further provides intermediates as well process for preparation thereof.
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Page/Page column 29; 30
(2015/01/06)
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- PPAR-SPARING COMPOUNDS FOR USE IN THE TREATMENT OF DIABETES AND OTHER METABOLIC DISEASES
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The present invention relates to compounds and pharmaceutical compositions that are useful for treating and/or preventing diabetes or other metabolic diseases, optionally in combination with a second therapy such an active pharmaceutical agent or diet restriction or an increase in duration or exertion in physical activity.
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Page/Page column 53
(2013/02/28)
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- NOVEL PHENYLPROPIONIC ACID DERIVATIVES AS PEROXISOME PROLIFERATOR-ACTIVATED GAMMA RECEPTOR MODULATORS, METHOD OF THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides a novel phenylpropionic acid derivative and a PPAR-γ modulator comprising the same as an active ingredient. The phenylpropionic acid derivative of the present invention has modulatory action on function of PPAR-γ and then exhibits hypoglycemic, hypolipidemic and insulin resistance-reducing effects on PPAR-mediated diseases or disorders. Therefore, the present invention is prophylactically or therapeutically effective for diabetes and metabolic diseases.
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Page/Page column 30
(2010/04/23)
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- Enzyme-mediated synthesis of EEHP and EMHP, useful pharmaceutical intermediates of PPAR agonists
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A new scaleable synthetic route to the title compounds has been developed. The reaction pathway is based on the α-chymotrypsin-catalysed hydrolysis of the racemic ethyl 2-ethoxy-3-(p-methoxyphenyl)propanoate or of the racemic ethyl 2-methoxy-3-(p-methoxyphenyl)propanoate to give the corresponding resolved (S)-esters with excellent ee. The acids were easily separated from the (S)-esters by a simple acid-base work-up. The overall yields of 1 and 2 were 16% and 17%, respectively.
- Brenna, Elisabetta,Fuganti, Claudio,Gatti, Francesco G.,Parmeggiani, Fabio
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experimental part
p. 2594 - 2599
(2010/03/30)
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- NOVEL ANTIDIABETIC COMPOUNDS
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The present invention provides novel compounds of the general formula (I), wherein the symbols are same as described in specification, their pharmaceutically acceptable salts, their tautomeric forms, their stereoisomers, pharmaceutical compositions containing them, to process and intermediates for the preparation of the above said compounds, having the utility of these compounds in medicine and to methods for their therapeutic use, and their use in the treatment of diabetes and related diseases.
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Page/Page column 85-86
(2010/11/29)
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- 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARα/γ agonists. Part I: Synthesis and pharmacological evaluation
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Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic β-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARα, PPARγ and PPARβ/(δ). We were interested in designing novel PPARγ selective agonists and/or dual PPARα/γ agonists. Based on the typical topology of synthetic PPAR agonists, we focused our design approach on 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as novel cyclic tail.
- Parmenon, Cecile,Guillard, Jerome,Caignard, Daniel-Henri,Hennuyer, Nathalie,Staels, Bart,Audinot-Bouchez, Valerie,Boutin, Jean-Albert,Dacquet, Catherine,Ktorza, Alain,Viaud-Massuard, Marie-Claude
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p. 1617 - 1622
(2008/09/19)
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- NOVEL PHENYLPROPIONIC ACID DERIVATIVES AS PEROXISOME PROLIFERATOR-ACTIVATED GAMMA RECEPTOR MODULATORS, METHOD OF THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides a novel phenylpropionic acid derivative and a PPAR-γ modulator comprising the same as an active ingredient. The phenylpropionic acid derivative of the present invention has modulatory action on function of PPAR-γ and then exhibits hypoglycemic, hypolipidemic and insulin resistance-reducing effects on PPAR-mediated diseases or disorders. Therefore, the present invention is prophylactically or therapeutically effective for diabetes and metabolic diseases.
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- Design, synthesis, and structure-activity relationship of carbamate-tethered aryl propanoic acids as novel PPARα/γ dual agonists
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We have developed a new class of PPARα/γ dual agonists, which show excellent agonistic activity in PPARα/γ transactivation assay. In particular, (R)-9d was identified as a potent PPARα/γ dual agonist with EC50s of 0.377 μM in PPARα and 0.136 μM in PPARγ, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARα/γ dual agonists significantly affects their agonistic activities in PPARα than in PPARγ.
- Kim, Nam-Jung,Lee, Kwang-Ok,Koo, Bon-Woong,Li, Funan,Yoo, Ja-Kyung,Park, Hyun-Ju,Min, Kyung-Hoon,Lim, Joong In,Kim, Mi Kyung,Kim, Jin-Kwan,Suh, Young-Ger
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p. 3595 - 3598
(2008/02/11)
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- A PHARMACEUTICAL COMPOSITION COMPRISING A SUBSTITUTED PHENYLPROPIONIC ACID AS A FREE ACID AND AS TERT-BUTYL AMINE SALT THEREOF
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A pharmaceutical composition comprising a compound of formula I wherein n is 1 or 2, R1 represents hydrogen, chloro, trifluoromethyl or trifluoromethoxy, R2 represents hydrogen or fluoro and R3 represents a C2-6alkyl group, wherein the compound of formula (I) is present in the composition as a free acid and as a tert-butyl amine salt thereof.
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Page/Page column 22
(2008/06/13)
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- PROCESS FOR PREPARING 3-ARYL-2-HYDROXY PROPANOIC ACID DERIVATIVES WITHOUT RESOLUTION
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The present invention discloses an improve process for the preparation of S (-) and R (+) 3-aryl-2-hydroxy propanoic acid derivatives without any resolution involved.
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Page/Page column 18
(2010/02/11)
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- Synthesis of a peroxime proliferator activated receptor (PPAR) α/γ agonist via stereocontrolled Williamson ether synthesis and stereospecific SN2 reaction of S-2-chloro propionic acid with phenoxides
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The stereospecific synthesis of the PPAR α/γ agonist 1 was accomplished via ethylation of the optically pure trihydroxy derivative 6, itself derived via an enzymatic resolution. The ethylation can be accomplished without epimerization only under strict control of the reaction conditions and the choice of base (sodium tert-amylate), temperature (-30°C), order of addition, and solvent (DMF). The key diastereospecific SN2 reaction of the phenol 4 with S-2-chloropropionic acid is best achieved via the sodium phenoxide of 4 derived from Na0 as the reagent of choice. The structure elucidation and key purification protocols to achieve pharmaceutical purity will also be described
- Aikins, James A.,Haurez, Michael,Rizzo, John R.,Van Hoeck, Jean-Pierre,Brione, Willy,Kestemont, Jean-Paul,Stevens, Christophe,Lemair, Xavier,Stephenson, Gregory A.,Marlot, Eric,Forst, Mindy,Houpis, Ioannis N.
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p. 4695 - 4705
(2007/10/03)
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- Claisen condensation as a facile route to an α-alkoxy-cinnamate: Synthesis of ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate
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The title compound was prepared from p-anisaldehyde and ethyl ethoxyacetate via a racemic synthetic route. The synthesis involves a Claisen-type condensation in which the elimination was unexpectedly promoted by an excess of the ester. The process has been successfully performed on a 2000-L scale with a total yield over seven steps of 19%.
- Linderberg, Mats T.,Moge, Mikael,Sivadasan, Sivaprasad
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p. 838 - 845
(2013/09/03)
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- THERAPEUTIC AGENTS
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The present invention provides the S enantiomer of a compound of formula (I) wherein R1 represents chloro, trifluoromethyl or trifluoromethoxy, R2 represents H or fluoro and R3 represents a C2-4alkyl group as well as pharmaceutically acceptable salts, solvates and prodrugs thereof, to processes for preparing such compounds, to their the utility in treating clinical conditions including lipid disorders (dyslipidemias) whether or not associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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- PHARMACEUTICALLY USEFUL SALTS OF CARBOXYLIC ACID DERIVATES
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A calcium or a magnesium salt of (2S)-2-ethoxy-3-(4-{2[hexyl(2-phenylethyl)amino]-2-oxoethoxy}phenyl)propanoic acid.
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Page/Page column 23-24
(2008/06/13)
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- Crystalline R-guanidines, arginine or (L)-arginine (2S)-2-ethoxy-3-{4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl}propanoate
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The present invention relates to crystalline R-guanidines of (2S)-2-Ethoxy-3-{4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl}propanoate, its preparations and its use as therapeutic agents. More specifically the present invention relates to crystalline Arginine (2S)-2-Ethoxy-3-{4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl}propanoate, preferably (L)-Arginine (2S)-2-Ethoxy-3-{4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl}propanoate, its preparation and its use as therapeutic agent.
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- Process for the preparation of new antidiabetic agents
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The present invention relates to an improved process for the preparation of novel antidiabetic compounds having formula (1) where R1represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom.
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- 3-aryl-2-hydroxypropionic acid derivative III
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A novel 3-aryl-2-hydroxypropionic acid derivative, a process and intermediate for its manufacture, pharmaceutical prepartions containing it and the use of the compound in clinical conditions associated with insulin resistance.
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- 3-aryl-2-hydroxypropionic acid derivative (I)
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A novel 3-aryl-2-hydroxypropionic acid derivative, a process and intermediate for its manufacture, pharmaceutical preparations containing it and the use of the compound in clinical conditions associated with insulin resistance.
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