73332-75-9Relevant academic research and scientific papers
Synthesis and in vitro evaluation of new 5-substituted 6-nitroimidazooxazoles as antikinetoplastid agents
Azas, Nadine,Cohen, Anita,Crozet, Maxime D.,Docampo, Roberto,Kabri, Youssef,Mathias, Fanny,Negr?o, Núria Waddington,Vanelle, Patrice
, (2020)
In continuation of our pharmacomodulation work on the nitroimidazooxazole series, we report the synthesis of new 5-substituted 6-nitroimidazooxazole derivatives. Our aim was to evaluate how functionalization of the 5-position of the 6-nitroimidazooxazole scaffold affects antileishmanial and antitrypanosomal in vitro activities. Twenty-one original compounds were synthesized and evaluated for their in vitro antileishmanial (L. donovani) and antitrypanosomal (T. cruzi) properties. Pallado-catalyzed cross-coupling reactions were used to introduce an aryl or ethynyl aryl substituent in 5-position from a 5-brominated-6-nitroimidazooxazole starting product. Unfortunately, the first series of compounds bearing an aryl group in 5-position presented limited in vitro activities against L. donovani and T. cruzi, with IC50 > 10 μM (vs 0.18 μM and 2.31 μM for the reference drugs amphotericin B and benznidazole respectively). Interestingly, the second series of compounds bearing an ethynyl aryl substituent in 5-position showed more promising, particularly against T. cruzi. Compounds 6a, 6b, 6c, 6g and 6h had better activity than the reference drug benznidazole (0.92 μM ≤ IC50 ≤ 2.18 μM vs IC50 = 2.31 μM), whereas the non-functionalized 2-methyl-6-nitro-2,3-dihydroimidazo [2,1-b]oxazole 2 was not active against T. cruzi (IC50 > 10 μM).
Synthesis of 2,3-dihydro-7-nitroimidazo[5,1-b]oxazoles as potential tuberculostatic agents
Zwawiak, Justyna,Olender, Dorota,Zwolska, Zofia,Augustynowicz-Kopec, Ewa,Zaprutko, Lucjusz
scheme or table, p. 229 - 233 (2009/04/04)
A series of 2,3-dihydro-7-nitroimidazo[5,1-b]oxazoles has been prepared in one-pot reaction. The proposed new method of their synthesis requires a treatment of 4,5-dinitroimidazole or 2-methyl-4,5-dinitroimidazole with oxiranes. Some of the obtained compounds have been tested in vitro for antimycobacterial activity and the spatial structure of them has been also discussed.
Nitroimidazoles: Part XX- Reactions of 2,4-Dinitroimidazoles with 2-Haloethanols, 3-Chloropropionitrile and Propylene Oxide
Nagarajan, K.,Shenoy, S. J.
, p. 363 - 368 (2007/10/02)
The reaction of 2,4-dinitroimidazole (1) with 2-chloroethanol, 3-chloroethanol, 3-chloropropanol or 3-chloropropionitrile gives 2-chloro-4-nitroimidazole (7) and not 4-chloro-5-nitroimidazole (3) as claimed in earlier literature. 1 and 2-bromoethanol likewise yield 2-bromo-4-nitroimidazole (11). 7 is methylated to isomeric methyl derivatives 8 and 13 and 11 to 12 and 14.In the reaction of 1 with 3-chloropropionitrile, other products 9, 10 and 16 have been isolated. 1 is unaffected by 2-chloropentane. 2-Chloroethanol and 1-methyl-2,4-dinitroimidazole (2) afford 8.HCl formed from hot 2-chloroethanol in the presence of nitroimdazoles seems to be responsible for the displacement of NO2 group at position-2 with chlorine. 1 and propylene oxide yield imidazooxazoline (18) and the dinitro alcohol (19) along with a small amount of the isomer 20. 19 is transformed to imidazooxazoline (21) by excess propylene oxide or piperidine. 7 and propylene oxide afford isomeric alcohols 26 and 27, the latter being readily transformed to 18.Piperidine opens the oxazoline ring 18 to yield 25. 1H NMR and 13C NMR data are used to derive new structures.
Potential Radiosensitizing Agents. 2. Synthesis and Biological Activity of Derivatives of Dinitroimidazole with Oxiranes
Sehgal, Raj K.,Webb, Matthew W.,Agrawal, Krishna C.
, p. 601 - 604 (2007/10/02)
A series of 1-substituted 2,4-dinitroimidazole analogues have been synthesized and tested for their radiosensitizing ability for selectively sensitizing hypoxic mammalian cells to the lethal effect of radiation.The reaction of 2,4(5)-dinitroimidazole (1) with a variety of oxiranes upon heating in absolute ethanol yielded the expected 1-substituted 2,4-dinitroimidazoles (2) and also resulted in the formation of a novel class of isomeric nitroimidazooxazoles (3 and 4) by intramolecular cyclization.The results of radiosensitizing activity of these agents against hypoxic Chinese hamster cells (V-79) indicated that 2,4-dinitroimidazoles were better sensitizers than the nitroimidazooxazoles, suggesting the necessity of the 2-nitro function in the molecule.The 1-(2-hydroxy-3-methoxypropyl)-2,4-dinitroimidazole (2d) was found to be the most effective radiosensitizer of this series.
