Synthesis, biological evaluation and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis

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Castagnolo, Daniele ; de Logu, Alessandro ; Radi, Marco ; Bechi, Beatrice ; Manetti, Fabrizio ; Magnani, Matteo ; Supino, Sibilla ; Meleddu, Rita ; Chisu, Lorenza ; Botta, Maurizio (2008)

As a continuation of our previous work that turned toward the identification of antimycobacterial compounds with innovative structures, two series of pyrazole derivatives were synthesized by parallel solution-phase synthesis and were assayed as inhibitors of Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis. One of these compounds showed high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazoles were also computationally investigated to analyze their fit properties to the pharmacophoric model for antitubercular compounds previously built by us and to refine structure–activity relationship analysis.
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