- Synthesis and antimicrobial evaluation of 3-methanone-6-substituted- benzofuran derivatives
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Seventeen benzofuran derivatives were synthesized and screened for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Seven of them have showed excellent antibacterial activities compared to the positive controls (Cefotaxime and Sodium Penicillin). The substitutions at C-6 and C-3 positions of these derivatives were found to greatly impact on the antibacterial activity and strains specificity, respectively. Specifically, compounds bearing a hydroxyl group at C-6 (5a, 5b, 5c and 12) offered excellent antibacterial activities against all five above-mentioned strains (MIC 80 = 0.78-12.5 ug/mL), and those with imine (15) and (3, 4, 5-trimethoxyphenyl) methanone (7e), respectively, at C-3 position showed selective activity against S. aureus among five tested strains with great MIC80 values (3.12-12.5 ug/mL).
- Liu, Jingbao,Jiang, Faqin,Jiang, Xizhen,Zhang, Wei,Liu, Jingjing,Liu, Wenlu,Fu, Lei
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experimental part
p. 879 - 886
(2012/09/10)
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- Design, synthesis and antimicrobial activity of chiral 2-(substituted- hydroxyl)-3-(benzo[d]oxazol-5-yl)propanoic acid derivatives
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Chiral 2-(substituted-hydroxyl)-3-(benzo[d]oxazol-5-yl)propanoic acid derivatives were synthesized and their antibacterial activities were evaluated against fungus, Gram-negative and Gram-positive bacteria. In general, these compounds showed in vitro acti
- Zhang, Wei,Liu, Wenlu,Jiang, Xizhen,Jiang, Faqin,Zhuang, Hao,Fu, Lei
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experimental part
p. 3639 - 3650
(2011/11/05)
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- (S)-3-(4-(2-(5-Methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(piperazin-1-yl)propanoic acid compounds: Synthesis and biological evaluation of dual PPARα/γ agonists
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A series of novel, potent PPARα/γ dual agonists were synthesized and appraised. The most potent analogue, compound 2b demonstrated EC50 value of 0.012 ± 0.002 and 0.032 ± 0.01 μM, respectively, for hPPARα and hPPARγ in transactivation assay. Additionally, compound 2b demonstrated good glucose and lipid lowering effect in genetic diabetic (db/db) mice.
- Zhou, Xinbo,Chen, Wei,Xu, Cheng,Fan, Shiyong,Xie, Yunde,Zhong, Wu,Wang, Lili,Li, Song
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scheme or table
p. 2605 - 2608
(2010/06/17)
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- TYROSINE DERIVATIVES SUBSTITUTED BY N-PHENYLACRYLOYL AS AGONISTS OF HPPAR ALPHA AND HPPAR GAMA
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The present invention relates to a compound of formula I, racemates, optically active isomers, or pharmaceutically acceptable salts or solvates thereof, and a pharmaceutical composition comprising the compound, the various radicals in the formula I are the same as defined in the claims. The present invention also relates to a process for preparing the compound of formula I and use of said compound in the preparation of a medicament for the treatment of hyperglycemia, dyslipidemia, type II diabetes mellitus including associated diabetic dyslipidemia
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Page/Page column 10
(2008/06/13)
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- Substitued A-Piperazingly Phenylpropionic Acid Derivatives As Hppar Alpha And/Or Hppar Gamma Agonists
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The present invention relates to a compound of formula I, racemates, optically active isomers, or pharmaceutically acceptable salts or solvates thereof, and a pharmaceutical composition comprising the compound, the various radicals in the formula I are the same as defined in the claims. The present invention also relates to a process for preparing the compound of formula I and use of said compound in the preparation of a medicament for the treatment of hyperglycemia, dyslipidemia, type II diabetes mellitus including associated diabetic dyslipidemia
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Page/Page column 8
(2008/06/13)
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- Process development and scale-up of AG035029
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A practical process for the synthesis of PPARγ agonist AG035029 was developed which involved six steps along the longest linear path. The process development utilized automated technology and computational chemistry extensively to accelerate the speed of
- Saenz, James,Mitchell, Mark,Bahmanyar, Sami,Stankovic, Nebojsa,Perry, Michael,Craig-Woods, Bridgette,Kline, Billie,Yu, Shu,Albizati, Kim
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- PROCESS FOR PREPARING OXAZOLE CARBOXYLIC ESTERS
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A process for preparing oxazole carboxylic esters of the formula (I) in which Ar is aryl or heteroaryl, Rl is H or alkyl and R2 is alkyl or aryl, which comprises converting an oxazole nitrile of the formula (II) in which Ar and Rl are as defined above, in the presence of a mineral acid and of ' an alcohol of the formula R20H, and subsequent hydrolysis with water, into the desired oxazole carboxylic esters of the formula (I) .
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Page/Page column 6
(2008/06/13)
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- NOVEL COMPOUNDS AS AGONIST FOR PPAR GAMMA AND PPAR ALPHA, METHOD FOR PREPARATION OF THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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The present invention relates to novel compounds accelerating the activity of Peroxisome proliferator-activated receptor gamma (PPARγ) and alpha (PPARα), processes of preparing the same, and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 97
(2010/02/11)
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- Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
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The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.
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Page 3; sheet 20
(2010/02/03)
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- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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- Substituted oxazoles and thiazoles derivatives as hPPARγ and hPPARα activators
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The present invention discloses compounds of formula (I), and tautomeric forms, pharmaceutically acceptable salts, or solvates thereof. Preferably, the compounds of the invention are dual activators of hPPARγ and hPPAR{acute over (α)}.
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- Process for the preparation of thiazolidinedione derivatives
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The present invention is concerned with a novel process for the preparation of compounds of formula I comprising bromomethylation or chloromethylation of a compound of formula II and subsequent reaction with a compound of formula IV The compounds of formu
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- Process for producing isoxazolidinedione compound
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The present invention relates to a novel method for producing a compound of the formula [11]wherein R is an optionally substituted aromatic hydrocarbon group, an optionally substituted alicyclic hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted condensed heterocyclic group, which is useful as a therapeutic agent for diabetes. The method of the present invention is an industrially utilizable method that enables efficient production of the objective compound [11] from β-methyl L-aspartate via an important intermediate compound [6]wherein R is as defined above, at high yield.
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- New azolidinediones as inhibitors of protein tyrosine phosphatase lb with antihyperglycemic properties
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Insulin resistance in the liver and peripheral tissues together with a pancreatic cell defect are the common causes of type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibiton of PTPases may be an effective method in the treatment of type 2 diabetes. A series of azolidinediones has been prepared as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Several compounds were Potent inhibitors against the recombinant rat and human PTP1B enzymes with submicromolar IC50 values. Elongated spacers between the azolidinedione moiety and the central aromatic portion of the molecule as well as hydrophobic groups at the vicinity of this aromatic region were very important to the inhibitory activity. Oxadiazolidinediones 87 and 88 and the corresponding acetic acid analogues 119 and 120 were the best h-PTP1B inhibitors with IC50 values in the range of 0.12-0.3 μM. Several compounds normalized plasma glucose and insulin levels in the ob/ob and db/db diabetic mouse models.
- Malamas, Michael S.,Sredy, Janet,Gunawan, Iwan,Mihan, Brenda,Sawicki, Diane R.,Seestaller, Laura,Sullivan, Donald,Flam, Brenda R.
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p. 995 - 1010
(2007/10/03)
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- Isoxazolidinedione compounds and use thereof
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Novel isoxazolidinedione derivatives of the formula (I) STR1 wherein R is an optionally substituted aromatic hydrocarbon, an optionally substituted alicyclic hydrocarbon, an optionally substituted heterocyclic group, an optionally substituted condensed he
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- Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5- lipoxygenase
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Azole phenoxy hydroxyureas are a new class of 5-lipoxygenase (5-LO) inhibitors. Structure-activity relationship studies have demonstrated that electronegative substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo potency of these
- Malamas,Carlson,Grimes,Howell,Glaser,Gunawan,Nelson,Kanzelberger,Shah,Hartman
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p. 237 - 245
(2007/10/03)
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- Thiazolidinedione derivatives as hypoglycemic agents
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Hypoglycemic thiazolidine-2,4-dione derivatives of the formula STR1 wherein the dotted line represents a bond or no bond; V is --CH=CH--, --N=CH--, --CH=N--, S, O or NR; W is S, SO, SO2, SO2 NR1, NR1 SO2/s
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- Studies on antidiabetic agents. 11. Novel thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents
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In the course of further chemical modification of the novel antidiabetic pioglitazone (AD-4833, U-72, 107), a series of 5-[4-(2- or 4- azolylalkoxy)benzyl- or -benzylidene]-2,4-thiazolidinediones was prepared and evaluated for hypoglycemic and hypolipidemic activities in insulin-resistant, genetically obese, and diabetic KKA(y) mice. Replacement of the 2-pyridyl moiety of pioglitazone by a 2- or 4-oxazolyl or a 2- or 4-thiazolyl moiety greatly enhanced in vivo potency. The corresponding 5-benzylidene-type compounds, in which a methine was used as a linker between the benzene ring and the thiazolidinedione ring, also had potent biological activity. Among the compounds synthesized, 5-[4-[2-(5-methyl-2-phenyl-4- oxazolyl)ethoxy]benzyl]-2,4-thiazolidinedione (18) exhibited the most potent activity, more than 100 times that of pioglitazone. The synthesis and structure-activity relationships for this novel series of derivatives are detailed.
- Sohda,Mizuno,Momose,Ikeda,Fujita,Meguro
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p. 2617 - 2626
(2007/10/02)
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- Novel Thiazolidine-2,4-diones as Potent Euglycemic Agents
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A new series of thiazolidine-2,4-diones was obtained by replacing the ether function of englitazone with various functional groups, i.e., a ketone, alcohol, or olefin moiety.These compounds lower blood glucose levels in the genetically obese and insulin-r
- Hulin, Bernard,Clark, David A.,Goldstein, Steven W.,McDermott, Ruth E.,Dambek, Paul J.,et al.
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p. 1853 - 1864
(2007/10/02)
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- Thiazolidinedione derivatives as hypoglycemic agents
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Hypoglycemic thiazolidine-2,4-dione derivatives of the formula wherein the dotted line represents a bond or no bond;, V is -CH=CH-, -N=CH-, -CH=N-, S, O or NR;, W is S, SO, SO2, SO2NR1, NR1SO2, CONR1 or NR1CO;, X is S, O,
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