N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors
| Autor: | Raj Kumar, Amit Agarwal, Manish K. Gupta, Kunal Nepali, Sameer Sapra, Naresh Kumar Satti, Om Parkash Suri, Vineet Mittal, Kanaya Lal Dhar, Uttam Chand Banerjee |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Models Molecular Xanthine Oxidase medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Stereoisomerism Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery medicine Animals Structure–activity relationship Enzyme Inhibitors Xanthine oxidase Molecular Biology Xanthine oxidase inhibitor Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Amides In vitro Dose–response relationship Xanthine dehydrogenase Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 19:5569-5576 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2011.07.039 |
| Popis: | A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC(50)=2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect