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Updated: Aug 13, 2026

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Development of atropisomeric 5N-sulfonyl-1,5-benzodiazepin-2-ones with high inhibitory activity against neutrophil
Hidetsugu Tabata1, Yoshiki Miyata1, Yoshio Kusakabe1
1Faculty of Pharmaceutical Sciences, Teikyo University 2-11-1 Kaga Itabashi-ku Tokyo 173-8605 Japan tabata.hidetsugu.ad@teikyo-u.ac.jp.
Abstract:
Novel 5N-sulfonyl-1,5-benzodiazepin-2-one derivatives (2b, d) with strong inhibition of neutrophil elastase have been developed. The atropisomers of 2d, based on the rotation of the two interlocking sp2-sp2 (Ar-N) axes [(aR, aR) and (aS, aS)], were stably isolated at room temperature by HPLC using a chiral column. A significant difference was observed in the inhibitory activity between the atropisomers [(+)-2d, (-)-2d, and (±)-2d], and the eutomer was revealed to be (+)-2d. The X-ray analysis revealed that the configuration of the eutomer (+)-2d was (aR, aR). The eutomer exhibited approximately 10-fold higher inhibitory activity than the currently used lead compound sivelestat (ONO-0546) (1), indicating its potential as a treatment for acute lung injury. Docking studies with target proteins supported our hypothesis of high activity.
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