Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: part 2. Synthesis of rigid pyrazolones.
Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC=4 microg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity.
Castagnolo
Daniele
D
Università degli Studi di Siena, via A. De Gasperi 2, 53100 Siena, Italy.
Manetti
Fabrizio
F
Radi
Marco
M
Bechi
Beatrice
B
Pagano
Mafalda
M
De Logu
Alessandro
A
Meleddu
Rita
R
Saddi
Manuela
M
Botta
Maurizio
M
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*; D014709:Vero Cells
D000995:Antitubercular Agents; D047069:Pyrazolones