630392-71-1

Basic information

• Product Name: Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-, (4-nitrophenyl)methyl ester
• CAS NO: 630392-71-1
• Molecular Formula: C11H16Cl2N3O4P
• Molecular Weight: 356.145
• Mol File: 630392-71-1.mol

Chemical Properties

• CAS DataBase Reference: Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-, (4-nitrophenyl)methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-, (4-nitrophenyl)methyl ester(630392-71-1)
• EPA Substance Registry System: Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-, (4-nitrophenyl)methyl ester(630392-71-1)

Safety Data

• Hazardous Substances Data: 630392-71-1(Hazardous Substances Data)

Upstream product

• 127-88-8 N,N-di(2-chloroethyl)amidophosphoric acid dichloride 
• 619-73-8 4-nitrobenzyl chloride 

Downstream Products

• 10159-53-2 phosphoramide mustard 

Relevant articles and documents

Nitroaryl Phosphoramides as Novel Prodrugs for E. coli Nitroreductase Activation in Enzyme Prodrug Therapy

Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC50 as low as 0.4 nM. This is about 100x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (kcat/Km 19x better than 1) and/or excellent cytotoxicity of phosphoramide mustard released.

Design, synthesis and evaluation of targeted hypoxia-activated prodrugs applied to chondrosarcoma chemotherapy

The tumor microenvironment in chondrosarcoma (CHS), a chemo- and radio-resistant cancer provides unique hallmarks for developing a chondrosarcoma targeted drug‐delivery system. Tumor targeting could be achieved using a quaternary ammonium function (QA) as a ligand for aggrecan, the main high negative charged proteoglycan of the extracellular matrix of CHS, and a 2-nitroimidazole as trigger that enables hypoxia‐responsive drug release. In a previous work, ICF05016 was identified as efficient proteoglycan-targeting hypoxia-activated prodrug in a human extraskeletal myxoid chondrosarcoma model in mice and a first study of the structure-activity relationship of the QA function and the alkyl linker length was conducted. Here, we report the second part of the study, namely the modification of the nitro-aromatic trigger and the position of the proteoglycan-targeting ligand at the aromatic ring as well as the nature of the alkylating mustard. Synthetic approaches have been established to functionalize the 2-nitroimidazole ring at the N-1 and C-4 positions with a terminal tertiary alkyl amine, and to perform the phosphorylation step namely through the use of an amine borane complex, leading to phosphoramide and isophosphoramide mustards and also to a phosphoramide mustard bearing four 2-chloroethyl chains. In a preliminary study using a reductive chemical activation, QA-conjugates, except the 4-nitrobenzyl one, were showed to undergo efficient cleavage with release of the corresponding mustard. However N,N,N-trimethylpropylaminium tethered to the N-1 or C-4 positions of the imidazole seemed to hamper the enzymatic reduction of the prodrugs and all tested compounds featured moderate selectivity toward hypoxic cells, likely not sufficient for application as hypoxia-activated prodrugs.

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Nitroaryl phosphoramide compositions and methods for targeting and inhibiting undesirable cell growth or proliferation

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