Abstract
A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).
MeSH terms
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Administration, Oral
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Animals
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Area Under Curve
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Benzamides / chemical synthesis*
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Benzamides / pharmacology
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Mice
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Mice, Inbred C57BL
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Models, Chemical
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Stearoyl-CoA Desaturase / antagonists & inhibitors*
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Stearoyl-CoA Desaturase / chemistry
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
Substances
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3-(2-hydroxyethoxy)-4-methoxy-N-(5-(3-trifluoromethylbenzyl)thiazol-2-yl)benzamide
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Benzamides
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Enzyme Inhibitors
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Thiazoles
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Stearoyl-CoA Desaturase