Abstract
The structure-activity relationship study of a small molecule Rev-erbα agonist is reported. The potency and efficacy of the agonists in a cell-based assay were optimized as compared to the initial lead. Modest mouse pharmacokinetics coupled with an improved in vitro profile make 12e a suitable in vivo probe to interrogate the functions of Rev-erbα in animal models of disease.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amines / chemical synthesis
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Amines / chemistry*
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Amines / pharmacokinetics
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Animals
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Benzylamines / chemical synthesis
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Benzylamines / chemistry*
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Benzylamines / pharmacokinetics
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Brain / metabolism
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Mice
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Nuclear Receptor Subfamily 1, Group D, Member 1 / agonists*
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Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
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Structure-Activity Relationship
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Thiophenes / chemical synthesis
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Thiophenes / chemistry*
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Thiophenes / pharmacokinetics
Substances
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Amines
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Benzylamines
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Nuclear Receptor Subfamily 1, Group D, Member 1
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Thiophenes