- TRICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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The present invention relates to tricyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)
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Page/Page column 48-49
(2012/09/10)
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- Method for producing tetrakis ( fluoroaryl) borate-magnesium compound
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Fluoroaryl magnesium halide is reacted with a boron compound so that a molar ratio of the fluoroaryl magnesium halide to the boron compound is not less than 3.0 and not more than 3.7, so as to produce a tetrakis (fluoroaryl) borate·magnesium compound. With this method, there occurs no hydrogen fluoride which corrodes a producing apparatus and requires troublesome waste water treatment.
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- Synthesis of 1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluoro-5- substituted-benzene thymidine mimics, some related α-anomers, and their evaluation as antiviral and anticancer agents
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A group of unnatural 1-(2-deoxy-β-D-ribofuranosyl)-2.4-difluorobenzenes having a variety of C-5 substituents (H, Me, F, Cl, Br, I, CF3, CN, NO2, NH2), designed as thymidine mimics, were synthesized for evaluation as anticancer and antiviral agents. The coupling reaction of 3,5-bis-O-(p-chlorobenzoyl) 2-deoxy-α-D-ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)2Cd] afforded a mixture of the α- and β-anomeric products (α:β = 3:1 to 10:1 ratio). Treatment of the α-anomer with BF3·Et2O in nitroethane at 110-120°C for 30 min was developed as an efficient method for epimerization of the major α-anomer to the desired β-anomer. The 5-substituted (H, Me, Cl, I, NH2) β-anomers exhibited negligible cytotoxicity in a MTT assay (CC50 = 10-3-10-4 M range), relative to thymidine (CC50 = 10-3-10-5 M range), against a variety of cancer cell lines. In contrast, the 5-NO2 derivative was more cytotoxic (CC50 = 10-5-10-6 M range). A number of 5-substituted β-anomers, and some related α-anomers, that were evaluated using a wide variety of antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia virus, vesicular stomatitis, cytomegalovirus (CMV) and human immunodeficiency (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleoside mimics are inactive antiviral agents.
- Wang,Duan,Wiebe,Balzarini,De Clercq,Knaus
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