Design and synthesis of disubstituted (4-piperidinyl)-piperazine derivatives as potent acetyl-CoA carboxylase inhibitors
| Autor: | Daisuke Yamamoto, Akira Hiratate, Hiroaki Tanaka, Tomomichi Chonan, Miyoko Yashiro, Hiroko Koretsune, Daisuke Wakasugi, Ayumi Ohoka-Sugita, Fusayo Io, Takahiro Oi |
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| Rok vydání: | 2010 |
| Předmět: |
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Molecular medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Crystallography X-Ray behavioral disciplines and activities Biochemistry Chemical synthesis Piperazines chemistry.chemical_compound Structure-Activity Relationship Piperidines Drug Discovery medicine Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Indole test biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Acetyl-CoA carboxylase Lipid metabolism Stereoisomerism Piperazine Enzyme Enzyme inhibitor Drug Design biology.protein Molecular Medicine Acetyl-CoA Carboxylase |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(13) |
| ISSN: | 1464-3405 |
| Popis: | Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the structure-based design and synthesis of a novel series of disubstituted (4-piperidinyl)-piperazine derivatives as ACC inhibitors. Our structure-based approach led to the discovery of the indole derivatives 13i and 13j, which exhibited potent in vitro ACC inhibitory activity. |
| Databáze: | OpenAIRE |
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