50700-55-5

Basic information

• Product Name: 1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid
• Synonyms: 1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid;1H-IMidazole-5-carboxylic acid, 1-Methyl-2-nitro-;1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid-6;EOS-61726
• CAS NO: 50700-55-5
• Molecular Formula: C₅H₅N₃O₄
• Molecular Weight: 171.1109
• Mol File: 50700-55-5.mol

Chemical Properties

• Boiling Point: 493.9±37.0 °C(Predicted)
• Appearance: /
• Density: 1.72±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 2.44±0.26(Predicted)
• CAS DataBase Reference: 1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid(50700-55-5)
• EPA Substance Registry System: 1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid(50700-55-5)

Safety Data

• Hazardous Substances Data: 50700-55-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-Methyl-2-nitro-1H-imidazole-5-carboxylic acid is used as a key intermediate in the synthesis of pharmaceuticals. Its presence in the molecular structure allows for the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid also serves as an intermediate in the production of agrochemicals, contributing to the development of new pesticides or other agricultural chemicals that can improve crop protection and yield.
Used in Dye and Pigment Manufacturing:
1-Methyl-2-nitro-1H-imidazole-5-carboxylic acid is utilized in the manufacturing of dyes and pigments due to its chemical properties that can impart color and stability to these products.
Used in Organic Compound Synthesis:
1-Methyl-2-nitro-1H-iMidazole-5-carboxylic acid is employed as a building block in the synthesis of other organic compounds, broadening its applications across various industries that rely on organic chemistry.

Upstream product

• 39070-13-8 ethyl 1-N-methyl-2-nitro-1H-imidazole-5-carboxylate 
• 40361-79-3 1-methyl-2-nitro-1H-imidazole-5-carboxylic acid methyl ester 
• 40361-77-1 2-amino-1-methyl-1H-imidazole-5-carboxylic acid methyl ester 

Downstream Products

• 67855-45-2 (6R)-3-methyl-7t-(3-methyl-2-nitro-3H-imidazole-4-carbonylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 39070-14-9 1-methyl-2-nitro-5-hydroxymethylimidazole 
• 304015-66-5 (1-methyl-2-nitro-1H-imidazol-5-yl)methyl (4-(hydroxymethyl)phenyl)carbamate 
• 304016-33-9 (1-methyl-2-nitro-1H-imidazol-5-yl)methyl (4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)carbamate 
• 39928-74-0 1-methyl-2-nitro-1H-imidazole-5-carbaldehyde 
• 246536-87-8 (1-methyl-2-nitro-1H-imidazol-5-yl)methyl (4-nitrophenyl) carbonate 

Relevant articles and documents

Rational Design for Nitroreductase (NTR)-Responsive Proteolysis Targeting Chimeras (PROTACs) Selectively Targeting Tumor Tissues

The catalytic properties of proteolysis targeting chimeras (PROTACs) may lead to uncontrolled off-tissue target degradation that causes potential toxicity, limiting their clinical applications. The precise control of this technology in a tissue-selective manner can minimize the potential toxicity. Hypoxia is a hallmark of most solid tumors, accompanied by elevated levels of nitroreductase (NTR). Based on this character, we presented a type of NTR-responsive PROTACs to selectively degrade proteins of interest (POI) in tumor tissues. Compound 17-1 was the first NTR-responsive PROTAC synthesized by incorporating the caging group on the Von Hippel-Lindau (VHL) E3 ubiquitin ligase ligand. It could be activated by NTR to release the active PROTAC 17 to efficiently degrade the EGFR protein and subsequently exert antitumor efficacy. Thus, a general strategy for the precise control of PROTAC to induce POI degradation in tumor tissues by NTR was established, which provided a generalizable platform for the development of NTR-controlled PROTACs to achieve selective degradation.

Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs

Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of structural modifications on drug binding to the enzymes: whereas the catalytic pocket of the epidermal growth factor receptor (EGFR) accepted all new erlotinib derivatives, the vascular endothelial growth factor receptor (VEGFR)-inhibitory potential in the case of the sunitinib prodrugs was dramatically diminished by derivatization. In line, hypoxia dependency of ERK signaling inhibition was observed with the sunitinib prodrugs, while oxygen levels had no impact on the activity of the erlotinib derivatives. Overall, proof of principle could be shown for this concept, and the results obtained are an important basis for the future development of tyrosine kinase inhibitor prodrugs.

TH-302 SOLID FORMS AND METHODS RELATED THERETO

The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.

PHOSPHORAMIDATE ALKYLATOR PRODRUGS

Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more anti-neoplastic agents.

Design, synthesis and evaluation of imidazolylmethyl carbamate prodrugs of alkylating agents

Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2- carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd.

A 2-nitroimidazole carbamate prodrug of 5-amino-1(chloromethyl)-3- [(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indole (amino- seco-CBI-TMI) for use with ADEPT and GDEPT

The synthesis of a 2-nitroimidazol-5-ylmethyl carbamate prodrug 10 of the potent minor groove alkylating agent amino-seco-CBI-TMI 3 is described. Chemical, radiolytic, and enzymic reductions of a model 2-nitroimidazol-5-yl carbamate 8 show release of the amine effector upon reduction. Prodrug 10 gives a ten fold increase in cytotoxicity against human ovarian carcinoma SKOV3 cells in the presence of E. coli B nitroreductase (NTR) and a 21-fold increase in cytotoxicity against a SKOV3 cell line (SC3.2) transfected with the gene for NTR. The cytotoxicity of 10 increased 15- to 40-fold under hypoxia. Prodrug 10 has significant potential as a prodrug for use in ADEPT and GDEPT applications, and as a hypoxia-selective cytotoxin.