Abstract
A series of tetrahydrobenzothiophene carboxamides, inspired by structural features present in kinase and SCD1 inhibitors, are presented here. Prototype compound 8 (MMDD13) modulates fatty acid elongase and desaturase indexes, lipid accumulation, while preserving kinase inhibitory activity. This chemotype represents a stepping stone towards chemical probes to study the consequences of lipid metabolism modulation through non-redundant pathways.
Copyright © 2017 Elsevier Ltd. All rights reserved.
MeSH terms
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Acetyltransferases / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Fatty Acid Desaturases / metabolism
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Fatty Acid Elongases
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Fatty Acids / metabolism*
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Humans
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Molecular Structure
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Protein Kinases / metabolism*
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Stearoyl-CoA Desaturase / antagonists & inhibitors*
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Stearoyl-CoA Desaturase / 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 / pharmacology*
Substances
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Enzyme Inhibitors
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Fatty Acids
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Thiophenes
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Fatty Acid Desaturases
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SCD1 protein, human
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Stearoyl-CoA Desaturase
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Acetyltransferases
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Fatty Acid Elongases
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Protein Kinases