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SAR study of 4-arylazo-3,5-diamino-1H-pyrazoles: identification of small molecules that induce dispersal of Pseudomonas aeruginosa biofilms†
Charlotte U. Jansen,Jesper Uhd,Jens B. Andersen,Louise D. Hultqvist,Tim H. Jakobsen,Martin Nilsson,Michael Givskov,Tim Tolker-Nielsen,Katrine M. Qvortrup
RSC Medicinal Chemistry Pub Date : 09/03/2021 00:00:00 , DOI:10.1039/D1MD00275A
Abstract

By screening of a collection of 50 000 small-molecule compounds, we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of anti-biofilm agents. Here, we report a SAR study based on 60 analogues by examining ways in which the pharmacophore can be further optimized, for example, via substitutions in the aryl ring. The SAR study revealed the very potent anti-biofilm compound 4-(2-(2-fluorophenyl)hydrazineylidene)-5-imino-4,5-dihydro-1H-pyrazol-3-amine (2).

Graphical abstract: SAR study of 4-arylazo-3,5-diamino-1H-pyrazoles: identification of small molecules that induce dispersal of Pseudomonas aeruginosa biofilms
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