- Aryl derivatives
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Novel compounds of formula (I) wherein: k, p and q are independently 0 or 1; Ar represents either: (i) naphthyl, tetrahydronaphthyl, pyridyl or (ii) phenyl, optionally substituted, L is selected from --(CH2)r -- (where r is 1-4), --O--, --CH2 O--, --CH2 S--, --OCH2 --, --CONH--, --NHCO--, --CO-- and --CH2 NH--, and, Ar' represents phenylene, thienylene or pyridylene optionally substituted, X represents oxygen, sulphur or carbonyl, Y is C1-10 alkylene or C1-10 alkenylene; Q represents a non-cyclic moiety selected from groups of formula STR1 in which one of m and n is 0 and the other is 1, R1 and R2 is selected from hydrogen, C1-4 alkyl, amino, C1-4 alkylamino, di-C1-4 alkylamino, C5-7 cycloalkylamino, C5-7 cycloalkyl (C1-4 alkyl) amino, anilino, N-C1-4 alkylanilino or Q represents a cyclic moiety selected from 1-hydroxy-1,3-dihydroimidazol-2-one and groups of formula STR2 in which Z represents a C2-5 alkylene chain in which one of the carbon atoms may be replaced by a hetero atom; and salts thereof.
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- Hydroxamic acid inhibitors of 5-lipoxygenase: Quantitative structure-activity relationships
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An evaluation of the quantitative structure-activity relationships (QSAR) for more than 100 hydroxamic acids revealed that the primary physicochemical feature influencing the in vitro 5-lipoxygenase inhibitory potencies of these compounds is the hydrophobicity of the molecule. A significant correlation was observed between the octanol-water partition coefficient of the substituent attached to the carbonyl of the hydroxamate and in vitro inhibitory activity. This correlation held for hydroxamic acids of diverse structure and with potencies spanning 4 orders of magnitude. Although the hydrophobicity may be packaged in a variety of structural ways and still correlate with potency, the QSAR study revealed two major exceptions. Specifically, the hydrophobicity of portions of compounds in the immediate vicinity of the hydroxamic acid functionally does not appear to contribute to increased inhibition and the hydrophobicity of fragments beyond approximately 12 A from the hydroxamate do not influence potency. The QSAR study also demonstrated that inhibitory activity was enhanced when there was an alkyl group on the hydroxamate nitrogen, when electron-withdrawing substituents were present and when the hydroxamate was conjugated to an aromatic system. These observations provide a simple description of the lipoxygenase-hydroxamic acid binding site.
- Summers,Kim,Mazdiyasni,Holms,Ratajczyk,Stewart,Dyer,Carter
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p. 992 - 998
(2007/10/02)
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- N-(3-phenoxycinnamyl)acetohydroxamic acid
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Novel compounds of formula (I) wherein: k, p and q are independently 0 or 1; Ar represents either: (i) naphthyl, tetrahydronaphthyl, pyridyl or (ii) phenyl, optionally substituted, L is selected from --(CH2)r -- (where r is 1-4), --O--, --CH2 O--, --CH2 S--, --OCH2 --, --CONH--, --NHCO--, --CO-- and --CH2 NH--, and, Ar' represents phenylene, thienylene or pyridylene optionally substituted, X represents oxygen, sulphur or carbonyl, Y is C1-10 alkylene or C1-10 alkenylene; Q represents a non-cyclic moiety selected from groups of formula STR1 in which one of m and n is 0 and the other is 1, R1 and R2 is selected from hydrogen, C1-4 alkyl, amino, C1-4 alkylamino, di-C1-4 alkylamino, C5-7 cycloalkylamino, C5-7 cycloalkyl (C1-4 alkyl) amino, anilino, N-C1-4 alkylanilino or Q represents a cyclic moiety selected from 1-hydroxy-1,3-dihydroimidazol-2-one and groups of formula STR2 in which Z represents a C2-5 alkylene chain in which one of the carbon atoms may be replaced by a hetero atom; and salts thereof.
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