SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors
| Autor: | Sheldon Crane, Lei Zhang, Jocelyne Guay, Sébastien Guiral, Chun Sing Li, Cameron Black, Lijing Xu, Yeeman K. Ramtohul, Renata Oballa, Zheng Huang, Chi-Chung Chan |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Clinical Biochemistry Administration Oral Pharmaceutical Science Type 2 diabetes Weight Gain Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound Internal medicine Drug Discovery medicine Animals Humans Hypoglycemic Agents Potency Enzyme Inhibitors Thiazole Molecular Biology Oxadiazoles Insulin Organic Chemistry Hep G2 Cells medicine.disease Dietary Fats Obesity Mice Inbred C57BL Thiazoles Stearoyl-CoA Desaturase Endocrinology chemistry Pharmacodynamics Molecular Medicine Metabolic profile |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:1593-1597 |
| ISSN: | 0960-894X |
| Popis: | 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 IC50 = 1 nM) 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 0.2 mg/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. |
| Databáze: | OpenAIRE |
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