Structure鈥揂ctivity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent

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• 作者：Le Chang ; Jessica D. Podoll ; Wei Wang ; Shane Walls ; Courtney P. O鈥橰ourke ; Xiang Wang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：May 8, 2014
• 年：2014
• 卷：57
• 期：9
• 页码：3803-3817
• 全文大小：385K
• 年卷期：v.57,no.9(May 8, 2014)
• ISSN：1520-4804

文摘

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 尾-lactam antibiotics. Herein, we report a thorough structure鈥揳ctivity 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.