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Bioorg Med Chem Lett ; 18(14): 3895-8, 2008 Jul 15.
Article in English | MEDLINE | ID: mdl-18590959

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.


Subject(s)
Chemistry, Pharmaceutical/methods , Diamines/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Epoxide Hydrolases/antagonists & inhibitors , Administration, Oral , Animals , Anti-Inflammatory Agents/pharmacology , Biological Availability , Diamines/chemistry , Dogs , Drug Design , Enzyme Inhibitors/pharmacology , Humans , Inhibitory Concentration 50 , Kinetics , Models, Chemical , Rats
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