40647-83-4

Upstream product

• 39928-74-0 1-methyl-2-nitro-1H-imidazole-5-carbaldehyde 
• 39070-14-9 1-methyl-2-nitro-5-hydroxymethylimidazole 
• 39070-12-7 C₇H₁₁N₃O₂*(x)ClH 
• 39070-13-8 ethyl 1-N-methyl-2-nitro-1H-imidazole-5-carboxylate 

Relevant academic research and scientific papers

Studies towards hypoxia-activated prodrugs of PARP inhibitors

Poly(ADP-ribose)polymerase (PARP) inhibitors (PARPi) have recently been approved for the treatment of breast and ovarian tumors with defects in homologous recombination repair (HRR). Although it has been demonstrated that PARPi also sensitize HRR competent tumors to cytotoxic chemotherapies or radiotherapy, normal cell toxicity has remained an obstacle to their use in this context. Hypoxia-activated prodrugs (HAPs) provide a means to limit exposure of normal cells to active drug, thus adding a layer of tumor selectivity. We have investigated potential HAPs of model PARPi in which we attach a bioreducible “trigger” to the amide nitrogen, thereby blocking key binding interactions. A representative example showed promise in abrogating PARPi enzymatic activity in a biochemical assay, with a ca. 160-fold higher potency of benzyl phthalazinone 4 than the corresponding model HAP 5, but these N-alkylated compounds did not release the PARPi upon one-electron reduction by radiolysis. Therefore, we extended our investigation to include NU1025, a PARPi that contains a phenol distal to the core binding motif. The resulting 2-nitroimidazolyl ether provided modest abrogation of PARPi activity with a ca. seven-fold decrease in potency, but released the PARPi efficiently upon reduction. This investigation of potential prodrug approaches for PARPi has identified a useful prodrug strategy for future exploration.

Compositions and methods for treating cancer

The invention provides a protected anti-neoplastic agent of the formula Hyp-N, wherein N is an anti-neoplastic agent and a protectable hydroxyl group of the anti-neoplastic is substituted with Hyp; Hyp is a moiety having the formula: wherein R 2 is hydrogen; R 3 is hydrogen or C 1 -C 6 alkyl; R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy, optionally substituted with one or more heteroatom-containing groups; and R 4 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 alkoxy, optionally substituted with one or more heteroatom-containing groups.

2-Nitroimidazole derivatives

2-Nitroimidazole derivatives of the general formula SPC1 Wherein R is a lower alkyl group and Y is a member of the group consisting of --CH2 OH, --CHO, CH3 CO--, vinyl, formylvinyl, styryl, substituted iminomethyl, 2-benzimidazolyl and 5-amino-1,3,4-thiadiazol-2-yl. The term "lower alkyl" designates aliphatic groups of from 1 to 4 carbon atoms; the term "substituted iminomethyl" designates nitrogen-containing functional derivatives of the aldehydic group. The compounds have antimicrobial activity.