doi: 10.1016/j.bmcl.2010.01.083.
Epub 2010 Jan 21.
SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors
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- PMID: 20137926
- DOI: 10.1016/j.bmcl.2010.01.083
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SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors
Bioorg Med Chem Lett.
.
Abstract
Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC(50)=1nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2mg/kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels.
Copyright 2010 Elsevier Ltd. All rights reserved.
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