14003-66-8Relevant articles and documents
Reactions of 1,4-dinitroimidazoles with hydrazines
Suwinski, Jerzy,Szczepankiewicz, Wojciech,Holt, Elizabeth M.
, p. 14905 - 14916 (1996)
Reaction of 2-methyl-1,4-dinitroimidazole with hydrazine results in expansion of the imidazole ring and formation of the 1.2.4-triazine derivative. Reaction of 1,4-dinitroimidazole with N-aminomorpholine yields 1-(N-morpholino)-4-nitroimidazole, by degenerative transformation of the imidazole ring. Treatment of 1,4-dinitroimidazoles with t-butoxycarbonylhydrazine results in the break down of the imidazole ring and formation of glyoxal dihydrazone derivatives. Structures of representative heterocyclic products were determined by X-ray analysis.
Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead
Chauvière, Gérard,Bouteille, Bernard,Enanga, Bertin,De Albuquerque, Cristina,Croft, Simon L.,Dumas, Michel,Périé, Jacques
, p. 427 - 440 (2007/10/03)
As part of our efforts to develop new compounds aimed at the therapy of parasitic infections, we synthesized and assayed analogues of a lead compound megazol, 5-(1-methyl-5-nitro-1H-2-imidazolyl)-1,3,4-thiadiazol-2-amine, CAS no. 19622-55-0), in vitro. We first developed a new route for the synthesis of megazol. Subsequently several structural changes were introduced, including substitutions on the two rings of the basic nucleus, replacement of the thiadiazole by an oxadiazole, replacement of the nitroimidazole part by a nitrofurane or a nitrothiophene, and substitutions on the exocyclic nitrogen atom for evaluation of an improved import by the glucose or the purine transporters. Assays of the series of compounds on the protozoan parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani, as either extracellular cells or infected macrophages, indicated that megazol was more active than the derivatives. Megazol was then evaluated on primates infected with Trypanosoma brucei gambiense, including late-stage central nervous system infections in combination with suramin. Full recovery was observed in five monkeys in the study with no relapse of parasitemia within a 2 year follow-up. Because there is a lack of efficacious treatments for sleeping sickness in Africa and Chagas disease in South America, megazol is proposed as a potential alternative. The mutagenicity of this compound is at present being reevaluated, and metabolism is also under investigation prior to possible further developments.
Electrophilic substitution reactions in heterocycles complexed to exchange-inert metal ions. (Ethylenediamine)cobalt(III) complexes of imidazole and histidine
Rowan-Gordon,Nguyenpho,Mondon-Konan,Turner,Butcher,Okonkwo,Hayden,Storm
, p. 4374 - 4380 (2008/10/08)
(Ethylenediamine)cobalt(III) complexes of imidazole and histidine are nitrated under mild conditions with a standard HNO3-H2SO4 nitrating mixture. In contrast to the more robust pentaamminecobalt(III) complexes, the nitrated imidazole ligand readily dissociates, providing an excellent synthetic route to a variety of nitroimidazoles. Pyridine coordinated to either Co(NH3)53+ or Co(en)2Cl2+ is not nitrated, even under conditions that destroy the complex. The difference in reactivity is evidently a reflection of the Co(III) d electron interaction with the lowest unoccupied molecular orbital (LUMO) of the ligand. The nucleophilic displacement of a nitro group by chloride in a coordinated nitroimidazole is also observed. Crystal data for bis(ethylenediamine)(benzimidazole)chlorocobalt(III) perchlorate, space group P1, Z = 4, a = 8.168 (4) ?, b = 11.570 (4) ?, c = 21.162 (8) ?, α = 78.93 (2)°, β = 78.87 (2)°, γ = 69.24 (2)°, and R = 6.67% for 3437 reflections; for bis(ethylenediamine)(pyridine)chlorocobalt(III) chloride, space group P21/n, a = 8.489 (3) ?, b = 14.021 (6) ?, c = 12.670 (6) ?, α = 90.0°, β = 91.63 (2)°, γ = 90.0°, and R = 4.11% for 2185 reflections; for bis(ethylenediamine)(4-nitroimidazolato)chlorocobalt(III) chloride hydrate, space group P1, a = 8.603 (5) ?, b = 7.358 (3) ?, c = 14.287 (7) ?, α = 95.82 (2)°, β = 86.79 (2)°, γ = 115.39 (2)°, and R = 5.21% for 5903 reflections; for bis(ethylenediamine)(4-chloroimidazole)chlorocobalt(III) chloride, space group C2/c, Z = 8, a = 23.550 (6) ?, b = 11.805 (2) ?, c = 12.128 (3) ?, α = 90.0°, β = 115.92 (2)°, γ = 90.0°, and R = 4.34% for 2377 reflections; and for (ethylenediamine)(4-nitrohistidinato-O,N,N′)chlorocobalt(III) hydrate, space group P21/n, a = 8.544 (3) ?, b = 17.382 (5) ?, c = 10.256 (3) ?, α = 90.0°, β = 107.50 (2)°, γ = 90.0°, and R = 5.60% for 2556 reflections, are reported.
