- Evaluation of fluorinated biphenyl ether pro-drug scaffolds employing the chemical-microbial approach
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Incorporation of fluorine in a drug can dramatically affect its metabolism and methods to assess the effect of fluorine substitution on drug metabolism are required for effective drug design. Employing a previously developed chemical-microbial method the metabolism of a series of fluorinated biphenyl ethers was determined. The substrates were synthesized via Ullmann-type condensation reactions between bromotoluene and fluorophenol. The ethers were incubated with the fungus Cunninghamella elegans, which oxidises xenobiotics in an analogous fashion to mammals, generating a number of hydroxylated biphenyl ethers and acids. The propensity of the fluorinated ring to be hydroxylated depended upon the position of the fluorine atom, and the oxidation of the methyl group was observed when it was meta to the oxygen. The experiments demonstrate the applicability of the method to rapidly determine the effect of fluorine substitution on CYP-catalysed biotransformation of pro-drug molecules.
- Hampton, Alex S.,Mikulski, Lena,Palmer-Brown, William,Murphy, Cormac D.,Sandford, Graham
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- Low catalyst loadings for copper-catalyzed O-arylation of phenols with aryl and heteroaryl halides under mild conditions
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A practical and mild strategy has been developed for the cross-coupling of O-arylation of phenol with differently substituted aryl halides and heteroaryl iodides using low catalyst loading of copper iodide under low operating temperature in DMF with TMHD as the ligand and Cs2CO3 as the base. This method tolerates a variety of functional groups including sterically hindered phenols and heteroaryl iodides to afford products in good to excellent yields (up to 95%). Georg Thieme Verlag Stuttgart. New York.
- Yong, Fui-Fong,Teo, Yong-Chua,Yan, Yaw-Kai,Chua, Guan-Leong
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p. 101 - 106
(2012/02/03)
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- N-[1-(3-phenoxyphenyl)ethyl]acetohydroxamic acid compounds which are useful anti-inflammatory agents
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The present invention provides compounds of formula (II) STR1 wherein q is 1, and p is 1; Ar is phenyl optionally substituted by one or more substitutents independently selected from C1-4 alkyl (which may be substituted by one or more halogen a
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- Anti-inflammatory aryl derivatives
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The present inventions concerned with compounds of formula (I) wherein, Ar is 4-halophenyl;, Ar? is 1,3- or 1,4-phenylene;, Y is (E)-CH=CH-; and, R1 and R2 are independently selected from hydrogen and C1-4alkyl;, and base salts and physiologica
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