Abstract
The synthesis and biological evaluation of a series of aryl diamines as inhibitors of LTA(4)-h inhibitors are described. The optimization which led to the identification of the optimal para-substitution on the diphenyl ether moiety and diamine spacer is discussed. The resulting compounds such as 3l have excellent enzyme and cellular potency as well as desirable pharmacokinetic properties.
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents / pharmacology
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Biological Availability
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Chemistry, Pharmaceutical / methods*
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Diamines / chemical synthesis*
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Diamines / chemistry
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Dogs
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Epoxide Hydrolases / antagonists & inhibitors*
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Humans
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Inhibitory Concentration 50
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Kinetics
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Models, Chemical
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Rats
Substances
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Anti-Inflammatory Agents
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Diamines
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Enzyme Inhibitors
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Epoxide Hydrolases
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leukotriene A4 hydrolase