84681-49-2

Upstream product

• 60106-92-5 N,N,N',N'-tetrakis(2-chloroethyl)phosphorodiamidic acid chloride 
• 100-51-6 benzyl alcohol 
• 870-24-6 2-chloroethanamine hydrochloride 
• 52692-02-1 benzyl phosphorodichloride 
• 84681-48-1 benzyl N,N'-bis(ethylene)phosphorodiamidate 

Downstream Products

• 845680-48-0 O-benzyl N-(2-bromoethyl)-N'-(2-chloroethyl)phosphorodiamidate 
• 84681-48-1 benzyl N,N'-bis(ethylene)phosphorodiamidate 
• 845680-46-8 O-benzyl aziridin-1-yl-N-(2-chloroethyl)phosphorodiamidate 
• 31645-39-3 ifosfamide mustard 

Relevant academic research and scientific papers

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.

SYNTHESIS AND FORMULATIONS OF SALTS OF ISOPHOSPHORAMIDE MUSTARD AND ANALOGS THEREOF

Disclosed herein are formulations and methods of manufacture of compounds of formula (E):wherein X and Y independently represent leaving groups; and A+ is an ammonium cation.

Synthesis of potential metabolites of (S)-(-)-bromofosfamide

(S)-(-)-Bromofosfamide, a newly obtained anticancer agent, recently became a subject of phase I clinical trials in Poland. With the aim to study its metabolism in humans using phosphorus nuclear magnetic resonance a group of potential metabolites of this agent was synthesized.