936-05-0Relevant articles and documents
Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells
Herrlinger, Eva-Maria,Hau, Mirjam,Redhaber, Desiree Melanie,Greve, Gabriele,Willmann, Dominica,Steimle, Simon,Müller, Michael,Lübbert, Michael,Miething, Christoph Cornelius,Schüle, Roland,Jung, Manfred
, p. 2329 - 2347 (2020/05/06)
Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR+. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.
Green synthesis method of Ronidazole and deuterated derivative thereof
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Paragraph 0048-0050, (2019/09/17)
The invention belongs to the technical field of chemical synthesis and discloses a green synthesis method of Ronidazole and a deuterated derivative thereof. The method comprises following steps: 4-nitroimidazole and methanol or deuterated methanol are subjected to a nitrogen methylation reaction or a nitrogen deuteration methylation reaction under the action of a catalyst, and 1-methyl-5-nitroimidazole or 1-trideuteromethyl-5-nitroimidazole is produced; the product and paraformaldehyde are subjected to a nucleophilic addition reaction, and 1-methyl-2-hydroxymethyl-5-nitroimidazole or 1-trideuteromethyl-2-hydroxymethyl-5-nitroimidazole is produced; the product of nucleophilic addition and urea are subjected to a heating reaction in the presence of an accelerant, and Ronidazole or the deuterated derivative thereof is produced. The raw materials are almost green reagents and are available and low in cost; conditions are simple, operation is easy, little pollution is produced, byproducts obtained in the three-step reaction are only water and ammonia gas, the post-processing method is simple, the product is easy to purify, and the yield is relatively ideal.
Compounds containing 2-substituted imidazole ring for treatment against human African trypanosomiasis
Samant, Bhupesh S.,Sukhthankar, Mugdha G.
supporting information; experimental part, p. 1015 - 1018 (2011/03/21)
A series of compounds containing 2-substituted imidazoles has been synthesized from imidazole and tested for its biological activity against human African trypanosomiasis (HAT). The 2-substituted 5-nitroimidazoles such as fexinidazole (7a) and 1-[4-(1-methyl-5-nitro-1H-imidazol-2-ylmethoxy)-pyridin-2- yl-piperazine (9e) exhibited potent activity against T. brucei in vitro with low cytotoxicity and good solubility. The presence of the NO2 group at the 5-position of the imidazole ring in 2-substituted imidazoles is the crucial factor to inhibit T. brucei.
