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

[Image: see text] 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 met...

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Autores principales: Chang, Le, Podoll, Jessica D., Wang, Wei, Walls, Shane, O’Rourke, Courtney P., Wang, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018117/
https://www.ncbi.nlm.nih.gov/pubmed/24694192
http://dx.doi.org/10.1021/jm500146g
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author Chang, Le
Podoll, Jessica D.
Wang, Wei
Walls, Shane
O’Rourke, Courtney P.
Wang, Xiang
author_facet Chang, Le
Podoll, Jessica D.
Wang, Wei
Walls, Shane
O’Rourke, Courtney P.
Wang, Xiang
author_sort Chang, Le
collection PubMed
description [Image: see text] 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.
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spelling pubmed-40181172015-04-02 Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent Chang, Le Podoll, Jessica D. Wang, Wei Walls, Shane O’Rourke, Courtney P. Wang, Xiang J Med Chem [Image: see text] 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. American Chemical Society 2014-04-02 2014-05-08 /pmc/articles/PMC4018117/ /pubmed/24694192 http://dx.doi.org/10.1021/jm500146g Text en Copyright © 2014 American Chemical Society
spellingShingle Chang, Le
Podoll, Jessica D.
Wang, Wei
Walls, Shane
O’Rourke, Courtney P.
Wang, Xiang
Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title_full Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title_fullStr Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title_full_unstemmed Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title_short Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent
title_sort structure–activity relationship studies of the tricyclic indoline resistance-modifying agent
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018117/
https://www.ncbi.nlm.nih.gov/pubmed/24694192
http://dx.doi.org/10.1021/jm500146g
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