Abstract
The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.
MeSH terms
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Administration, Oral
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Animals
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Enzyme Inhibitors / chemistry*
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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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Mice
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Piperidines / chemistry*
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Piperidines / pharmacology*
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacology*
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Structure-Activity Relationship
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beta-Alanine / analogs & derivatives*
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beta-Alanine / chemistry*
Substances
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Enzyme Inhibitors
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Piperidines
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Pyrrolidines
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SC 57461
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SC56938
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beta-Alanine
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Epoxide Hydrolases
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leukotriene A4 hydrolase