Abstract
A series of novel 2-azabicyclo[2.2.2]octane derivatives was synthesized and evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Screening of our corporate chemical collections against ELOVL6 resulted in the identification of lead 1. Exploratory chemistry efforts were applied to lead 1 to identify the orally available, potent, and selective ELOVL6 inhibitor 28a.
MeSH terms
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Acetyltransferases / antagonists & inhibitors*
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Acetyltransferases / metabolism*
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Animals
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Azabicyclo Compounds / chemical synthesis
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Azabicyclo Compounds / chemistry*
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Azabicyclo Compounds / pharmacokinetics
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Azabicyclo Compounds / pharmacology*
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Fatty Acid Elongases
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Fatty Acids / metabolism
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Humans
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Liver / enzymology
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Male
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Mice
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Mice, Inbred C57BL
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Octanes / chemical synthesis
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Octanes / chemistry*
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Octanes / pharmacokinetics
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Octanes / pharmacology*
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Structure-Activity Relationship
Substances
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Azabicyclo Compounds
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ELOVL6 protein, human
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Elovl6 protein, mouse
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Fatty Acids
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Octanes
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Acetyltransferases
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Fatty Acid Elongases
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octane