On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method...On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.展开更多
A new series of sulfonamide flavone derivatives are designed as non-covalent inhibitors of proteasome assisted with computer-aided drug design (CADD). The desired compounds were synthesized successfully and the biol...A new series of sulfonamide flavone derivatives are designed as non-covalent inhibitors of proteasome assisted with computer-aided drug design (CADD). The desired compounds were synthesized successfully and the biological evaluation was subsequently accomplished. The results showed negligible improvement from our lead compound (IC50 for β5 subunit was 14.0 μM). Thus, these flavone derivatives might be improved as potential 20S proteasome inhibitors.展开更多
基金Natural Science Foundation of China for the financial support(Grant No.30772626)
文摘On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.
基金The National Natural Science Foundation of China(Grant No.21202003)the National Basic Research Program of China(Grant No.2012CB518000)the Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20120001110010)
文摘A new series of sulfonamide flavone derivatives are designed as non-covalent inhibitors of proteasome assisted with computer-aided drug design (CADD). The desired compounds were synthesized successfully and the biological evaluation was subsequently accomplished. The results showed negligible improvement from our lead compound (IC50 for β5 subunit was 14.0 μM). Thus, these flavone derivatives might be improved as potential 20S proteasome inhibitors.