1944-96-3

Basic information

• Product Name: Hydroxylamine, O-[(4-nitrophenyl)methyl]-
• CAS NO: 1944-96-3
• Molecular Formula: C7H8N2O3
• Molecular Weight: 168.152
• Mol File: 1944-96-3.mol
• Article Data: 13

Chemical Properties

• CAS DataBase Reference: Hydroxylamine, O-[(4-nitrophenyl)methyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: Hydroxylamine, O-[(4-nitrophenyl)methyl]-(1944-96-3)
• EPA Substance Registry System: Hydroxylamine, O-[(4-nitrophenyl)methyl]-(1944-96-3)

Safety Data

• Hazardous Substances Data: 1944-96-3(Hazardous Substances Data)

Upstream product

• 64583-54-6 N-Benzoyl-O-p-nitrobenzylhydroxylamine 
• 30777-85-6 N-phthalimido-O-(p-nitrobenzyl)-hydroxylamine 
• 100-11-8 1-bromomethyl-4-nitro-benzene 
• 619-73-8 4-nitrobenzyl chloride 
• 100-14-1 4-nitrobenzyl chloride 

Downstream Products

• 54837-27-3 N-p-Nitrobenzyloxy-DL-Alanin 
• 681146-18-9 2-[2-(4-nitro-benzyloxyamino)-ethyl]-isoindole-1,3-dione 
• 2086-26-2 O-(p-nitrobenzyl)hydroxylamine hydrochloride 
• 1382748-78-8 C₉H₈N₄O₅ 
• 1382748-83-5 C₁₂H₁₂N₄O₅ 
• 1351934-69-4 1-(((4-nitrobenzyl)oxy)amino)-4-propoxy-9H-thioxanthen-9-one 
• 1273536-12-1 4-benzoyl-N-(4-nitrobenzyloxy)-1,5-diphenyl-1H-pyrazole-3-carboxamide 

Relevant articles and documents

Zap-Pano: a Photocaged Prodrug of the KDAC Inhibitor Panobinostat

We report the synthesis and biological evaluation of a light-activated (caged) prodrug of the KDAC inhibitor panobinostat (Zap-Pano). We demonstrate that addition of the 4,5-dimethoxy-2-nitrobenzyl group to the hydroxamic acid oxygen results in an inactive prodrug. In two cancer cell lines we show that photolysis of this compound releases panobinostat and an unexpected carboxamide analogue of panobinostat. Photolysis of Zap-Pano causes an increase in H3K9Ac and H3K18Ac, consistent with KDAC inhibition, in an oesophageal cancer cell line (OE21). Irradiation of OE21 cells in the presence of Zap-Pano results in apoptotic cell death. This compound is a useful research tool, allowing spatial and temporal control over release of panobinostat.

Hypoxia-activated pro-drugs of the KDAC inhibitor vorinostat (SAHA)

Hypoxia (lower than normal oxygen) is a characteristic of most solid tumours that results in poor cancer patient prognosis. The difference in cellular environment between normoxia (21percent oxygen) or physoxia (4–7.5percent oxygen) and hypoxia (2.0percent oxygen) causes increased resistance to radio- and chemotherapy, but also provides the opportunity to selectively release hypoxia-activated pro-drugs. This approach potentially allows targeting of chemotherapies, including lysine deacetylase (KDAC) inhibitors, to the hypoxic fraction of cells. Here, we report initial work on the development of KDAC inhibitors that are selectively released in hypoxic conditions. We have shown that the addition of a 4-nitrobenzyl (NB) or 1-methyl-2-nitroimidazole (NI) bioreductive group onto the hydroxamic acid moiety of SAHA, giving NB-SAHA and NI-SAHA, abolishes KDAC inhibition activity. Both NB-SAHA and NI-SAHA undergo enzyme-mediated bioreduction, in a hypoxia-dependent manner, to release SAHA selectively in 0.1percent oxygen. This work provides an important foundation for further investigations into the targeted release of KDAC inhibitors in hypoxic tumours.

O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.