202124-46-7Relevant academic research and scientific papers
Structure based optimization of chromen-based TNF-α converting enzyme (TACE) inhibitors on S1′ pocket and their quantitative structure-activity relationship (QSAR) study
Yang, Jee Sun,Chun, Kwangwoo,Park, Jung Eun,Cho, Misun,Seo, Jeongjea,Song, Doona,Yoon, Hongchul,Park, Chun-Ho,Joe, Bo-Young,Choi, Jong-Hee,Kim, Myung-Hwa,Han, Gyoonhee
experimental part, p. 8618 - 8629 (2011/02/25)
A series of coumarin based TACE inhibitors were designed to bind in S1′ pocket of TACE enzyme based on their docking study. Twelve analogues were synthesized and most of compounds were active in vitro TACE enzyme inhibition as well as cellular TNF-α inhibition. Among these, 15l effectively inhibited the production of serum TNF-α by oral administration at a dose of 30 mg/kg. Compound 15l also showed a good oral bioavailability at 42% and effectively inhibited paw edema in rat carrageenan model. Quantitative structure-activity relationship (QSAR) study using genetic function approximation technique (GFA) and docking study were performed to confirm the series of coumarin core TACE inhibitors. QSAR model have been evaluated internally and externally using test set prediction. Through docking study of each molecule, it is validated that the electrostatic descriptors from the QSAR equation could explain the importance of S1′ pocket and the TACE inhibitory activity well.
Discovery of novel hydroxamates as highly potent tumor necrosis factor-α converting enzyme inhibitors. Part II: Optimization of the S3′ pocket
Mazzola Jr., Robert D.,Zhu, Zhaoning,Sinning, Lisa,McKittrick, Brian,Lavey, Brian,Spitler, James,Kozlowski, Joseph,Neng-Yang, Shih,Zhou, Guowei,Guo, Zhuyan,Orth, Peter,Madison, Vincent,Sun, Jing,Lundell, Daniel,Niu, Xiaoda
scheme or table, p. 5809 - 5814 (2009/06/30)
A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibi
NOVEL CHROMEN-2-ONE BASED HYDROXAMIC ACID DERIVATIVES HAVING ANTI-INFLAMMATORY ACTIVITY, THE PREPARATION THEREOF AND A COMPOSITION CONTAINING THE SAME FOR TREATING INFLAMMATORY DISEASE
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Page/Page column 37, (2010/11/25)
The present invention relates to novel chromen-2-one based hydroxamic acid derivatives having anti-inflammatory activity, the preparation thereof and a composition containing the same for treating inflammatory disease.
