Discovery of novel 20S proteasome inhibitors by rational topology-based scaffold hopping of bortezomib. Issue 12 (1st July 2018)

• Record Type: Journal Article
• Authors: Xu, Yulong; Yang, Xicheng; Chen, Yiyi; Chen, Hao; Sun, Huijiao; Li, Wei; Xie, Qiong; Yu, Linqian; Shao, Liming
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 12(2018)
• Page Start: 2148
• Page End: 2152
• Publication Date: 2018-07-01
• Subjects: Proteasome inhibitors -- Topology-based -- Scaffold hopping -- Bortezomib; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.05.018
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Twelve structurally novel proteasome inhibitors have been developed. Rational topology-based scaffold hopping of bortezomib has been employed. One of the compounds represents an important advance. Abstract: A series of structurally novel proteasome inhibitors 1 –12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50 = 9.7 nM) to bortezomib (IC50 = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.