Designing New 5-Nitroimidazoles: Towards Safer Anti-infectious Agents

Functionalized Nitroimidazole Scaffold Construction and Their Pharmaceutical Applications: A 1950–2021 Comprehensive Overview

“…The 5-nitroimidazole scaffold [ 6 ] was the starting point to the synthesis of numerous analogs, and one among such is Metronidazole 7 ((Flagyl ® , Rhône-Poulenc, France), which has shown potent anti-protozoal activity and lesser toxicity than Azomycin 1 ( Figure 3 ) [ 7 ]. Metronidazole 7 was the first systemically active medicine against Trichomonas vaginalis and Trichomonas foetus .…”

“…The 5-nitroimidazole moiety is well known for its broad spectrum of anti-infectious activity [ 9 ]. A specific review on the anti-infectious activity of 5-nitroimidazole has been emphasized by Crozet et al [ 6 ]. For instance, Metronidazole 7 (Flagyl ® , developed by Rhône-Poulenc, France), Tinidazole 8 (Fasigyne ® , developed by Pfizer, Brooklyn, NY, USA), Ornidazole 9 (Tiberal ® , developed by Hoffmann-La Roche, Basel, Switzerland), Satranidazole 10 , Nimorazole 11 (Nitrimidazine, Naxogin ® , developed by Carlo Erba, Cornaredo, Italy), Secnidazole 12 (Secnol ® , developed by Symbiomix, Newark, NJ, USA), and Dimetridazole 13 (Emtryl ® , developed by Rhône-Poulenc, France) are other members of this class of drugs commonly used in medicine.…”

“…Considering its wide and interesting biological activities, several reviews and books were published. However, most of them were focused on their pharmacological profiles [ 1 , 6 , 18 , 22 , 23 , 24 , 25 ]. There are few reviews that cover the partial synthetic aspects of this scaffold [ 26 , 27 , 28 ], and considering its wide application and the presence of diverse space around this scaffold, there should be a consolidated review covering chemistry, pharmacological and recent development.…”

An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities

“…Therefore, there is an ongoing search for alternative 5-nitroimidazoles effective on anaerobic-resistant strains without serious adverse effects [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Following the work of Walsh et al in 1987 [ 49 ], we focused our research on pharmacomodulation of the 2- and 4-positions of the 5-nitroimidazole scaffold [ 50 ].…”

“…As part of our research program centered on the design and synthesis of novel 5-nitroimidazole compounds [ 40 , 43 , 48 , 50 , 59 , 60 ], we decided to exploit this particular reactivity of the 5-nitroimidazole series toward cross-coupling reactions, seeking a rapid and versatile pathway for the synthesis of 2,4-disubstitued 5-nitroimidazole derivatives. Therefore, we report herein a regioselective Suzuki-Miyaura cross-coupling between 2,4-dibromo-1-methyl-5-nitro-1 H -imidazole ( 2 ) and aryl or heteroarylboronic acids resulting in the formation of 2-bromo-4-substituted-1-methyl-5-nitroimidazoles which can then undergo a second (Suzuki-Miyaura or Sonogashira) cross-coupling reaction to obtain 2,4-disubstituted 5-nitroimidazoles during a sequential one-pot process.…”