Structure?Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent

摘要

Previously we discovered a tricyclic indoline, N- [2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol- 4a-yl)ethyl]-4-chlorobenzene-1-sulfonamide (1, Of1), from bioinspired synthesis of a highly diverse polycyclic indoline alkaloid library, that selectively resensitizes methicillin-resistant Staphylococcus aureus strains to β-lactam antibiotics. Herein, we report a thorough structure?activity relationship investigation of 1, which identified regions of 1 that tolerate modifications without compromising activity and afforded the discovery of a more potent analogue with reduced mammalian toxicity.