Nouveaux 5-nitroimidazoles à noyau lactame hautement actifs : préparation et propriétés antibactériennes

Studies on antiparasitic agents: effect of the lactam nucleus substitution in the 2-position on the in-vitro activity of new 5-nitroimidazoles

“…Chemistry. 5-Nitroimidazole derivatives bearing a trisubstituted ethylenic double bond in the 2-position were prepared by reacting 1 -alkyl-2-chloromethyl-5-nitroimidazoles with 3-nitrolactam anions under phase-transfer catalysis (Jentzer et al 1991). These new compounds were identified by spectral data and their purity established by controls on thin-layer chromatography and microanalysis.…”

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

“…There have been several pharmacomodulation attempts to improve metronidazole activity on parasites such as Giardia intestinalis or Trichomonas vaginalis , and on anaerobic bacteria of the Clostridium and Bacteroïdes species . Previously, we synthesized a 2‐substituted 5‐nitroimidazole by unimolecular radical nucleophilic substitution (S RN 1), RP 57967, which was shown to be fivefold more active than metronidazole against Clostridium perfringens with higher mutagenicity (Figure ) . Extending our research program, we obtained a 4‐substituted 5‐nitroimidazole with a chlorophenylmethylsulfone moiety by vicarious nucleophilic substitution of hydrogen (VNS) .…”

“…[14,15] Previously,w es ynthesized a2 -substituted5 -nitroimidazole by unimolecular radical nucleophilic substitution (S RN 1), RP 57967, which was shown to be fivefold more active than metronidazole against Clostridium perfringens with higherm utagenicity ( Figure 1). [16][17][18][19] Extendingo ur research program, [20,21] we obtained a4-substituted5-nitroimidazole with achlorophenylmethylsulfone moiety by vicarious nucleophilic substitution of hydrogen (VNS). [22] This compound was characterized by lower mutagenicity and highera ntiparasitica ctivity than metronidazole ( Figure 1).…”

Mechanistic Investigation of the Ring Opening in the Staudinger Cycloaddition Involving Ketenes with Electron‐Withdrawing Substituents

“…In these preparations, no ring-opening reaction was observed, revealing that 3-nitro-b-lactam carbanions cannot convert to the corresponding a,bunsaturated nitroalkenamides [14] [15]. The azaenolate C with an electronwithdrawing substituent can produce both the a,b-unsaturated alkenamide 6 and the trans-b-lactam (AE)-1 if k a is close to k t .…”