- Characterization of 3,3-dimethyl substituted N-aryl piperidines as potent microsomal prostaglandin E synthase-1 inhibitors
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Here we report on novel, potent 3,3-dimethyl substituted N-aryl piperidine inhibitors of microsomal prostaglandin E synthases-1(mPGES-1). Example 14 potently inhibited PGE2synthesis in an ex vivo human whole blood (HWB) assay with an IC50
- Kuklish, Steven L.,Antonysamy, Stephen,Bhattachar, Shobha N.,Chandrasekhar, Srinivasan,Fisher, Matthew J.,Fretland, Adrian J.,Gooding, Karen,Harvey, Anita,Hughes, Norman E.,Luz, John G.,Manninen, Peter R.,McGee, James E.,Navarro, Antonio,Norman, Bryan H.,Partridge, Katherine M.,Quimby, Steven J.,Schiffler, Matthew A.,Sloan, Ashley V.,Warshawsky, Alan M.,York, Jeremy S.,Yu, Xiao-Peng
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- Modulators of Protein Tyrosine Phosphatases (PTPases)
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Disclosed are novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds of Formula 1 are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases) such as PTP1B, CD45, SHP-1, SHP-2, PTPα, LAR and HePTP or the like, wherein n, m, X, Y, R1, R2, R3, R4, R5 and R6 are defined more fully in the description. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, and other diseases.
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Page/Page column 37
(2010/10/20)
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- Method of inhibiting protein tyrosine phosphatase 1B and/or T-cell protein tyrosine phosphatase 4 and/or other PTPases with an Asp residue at position 48
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The present invention provides a method of inhibiting a member of a family of Protein Tyrosine Phosphatases (PTPases, PTPs) such as PTP1B, TC-PTP, CD45, SHP-1, SHP-2, PTPα, PTPε, PTPμ, PTPδ, PTPσ, PTPζ, PTPβ, PTPD1, PTPD2, PTPH1, PTP-MEG1, PTP-LAR, and HePTP by exposing said Ptpase member by administration to a host or otherwise to at least one compound with certain structural, physical and spatial characteristics that allow for the interaction of said compound with specific residues of the active site of PTP1B and/or TC-PTP. These compounds are indicated in the management or treatment of a broad range of diseases such as autoimmune diseases, acute and chronic inflammation, osteoporosis, various forms of cancer and malignant diseases, and type I diabetes and type II diabetes, as well as in the isolation of PTPases and in elucidation or further elucidation of their biological function.
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Page/Page column 54-55
(2010/11/23)
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- A Lewis Base-catalyzed hetero Diels-Alder reaction between aldehydes and the Danishefsky's diene
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A lithium methoxide-catalyzed hetero Diels-Alder reaction of aromatic and aliphatic aldehydes with 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky's diene) is described. It proceeds through the Mukaiyama-Aldol reaction pathway and affords the cor
- Mukaiyama, Teruaki,Kitazawa, Takayuki,Fujisawa, Hidehiko
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p. 328 - 329
(2007/10/03)
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- Hetero diels-alder type reactions between danishefsky's dienes in the presence of lewis base catalysts. An efficient method for the synthesis of substituted 2,3-dihydropyran-4-ones
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Alkoxy anion such as methoxide anion works effectively as Lewis base catalyst to activate silicon-carbon bond of 1-methoxy-3-trimethylsilyloxy-1,3-butadiens (Danishefsky's dienes) in the reaction between aldehydes and ketones. By using Lewis base as catal
- Kitazawa, Takayuki,Mukaiyama, Teruaki
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p. 417 - 427
(2008/02/09)
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- MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPases)
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Disclosed are novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds of Formula 1 are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases) such as PTP1B, CD45, SHP-1, SHP-2, PTPalpha, LAR and HePTP or the like, wherein n, m, X, Y, R1, R2, R3, R4, R5 and R6 are defined more fully in the description. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, and other diseases.
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Page/Page column 25-26
(2010/02/14)
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- Preparation and reactions of 2-allyl-5-deoxymannose derivatives
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Reaction of Danishefsky diene with benzyloxyethanal led to a pyrone which was transformed in 4-6 steps to different 5-deoxymannose derivatives, useful intermediates for the synthesis of natural product such as hemibrevetoxin.
- Saleh, Twana,Rousseau, Gérard
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p. 2891 - 2897
(2007/10/03)
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- Preparation of (+/-)-1-Allyl-4-deoxy Mannose Derivatives
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Preparation of 4-deoxy mannose intermediates, useful for the synthesis of hemibrevetoxin is reported by a short reaction pathway. - Keywords: hemibrevetoxin; hetero Diels-Alder; allylation; iodoetherification; 4-deoxy mannose
- Saleh, Twana,Rousseau, Gerard
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p. 617 - 619
(2007/10/03)
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- Synthesis of C-disaccharides via glucal dimerisation
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Treatment of 3-O-acetyl glucal and related species with acetylperchlorate provides good yields of the corresponding C-disaccharides with a high degree of stereocontrol at the new C-C bond. Copyright (C) 1996 Elsevier Science Ltd.
- Byerley, Andrew L. J.,Kenwright, Alan M.,Steel, Patrick G.
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p. 9093 - 9096
(2007/10/03)
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- Stereoselective aldol reactions of β-chlorovinyl ketones using dienol borinates: A new synthesis of dihydropyrones
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The syn-selective aldol reaction of β-chlorovinyl ketones using dienol borinates can be coupled with a trimethylsilyltriflate promoted cyclisation to give cis-dihydropyrones, 4 6 7. Use of dienol diisopinoeampheylborinates leads to an enantioselective synthesis of dihydropyrones.
- Paterson, Ian,Osborne, Simon
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p. 2213 - 2216
(2007/10/02)
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- A Nitrile Oxide Based Entry to 2,3-Dihydropyran-4-ones. Synthesis of a Protected Version of "Compactin Lactone" in Racemic and Optically Active Forms
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The use of nitrile oxides bearing a masked β-oxo group as β-hydroxy-3-oxopropionylating agents for the vicinal functionalization of olefins is described.The β-hydroxy ketones revealed on hydrogenation of the initially formed 1,3-dipolar cycloaddition prod
- Kozikowski, Alan P.,Li, Chun-Sing
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p. 778 - 785
(2007/10/02)
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