18228-80-3Relevant academic research and scientific papers
Design, synthesis and evaluation of targeted hypoxia-activated prodrugs applied to chondrosarcoma chemotherapy
Canitrot, Damien,Chezal, Jean-Michel,Galmier, Marie-Josephe,Gaumet, Vincent,Gerard, Yvain,Ghedira, Donia,Maubert, Elise,Miot-Noirault, Elisabeth,Peyrode, Caroline,Tarrit, Sebastien,Voissière, Aurélien,Weber, Valérie
supporting information, (2020/04/08)
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.
HYDROXY-BISPHOSPHONIC ACID DERIVATIVES AS VECTOR TARGETING BONE TISSUE
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Page/Page column 12, (2010/12/29)
The present invention relates to hydroxy-bisphosphonic acid derivatives corresponding to general formula (I): in which: -n and m denote, independently of one another, an integer ranging from 1 to 4, —X denotes an oxygen atom or an N—R3 group, —R1 and R3 denote, independently of one another, a linear or branched C1 to C6 alkyl group, and —R2 denotes a residue of a molecule of therapeutic or diagnostic interest, or pharmaceutically acceptable salts of said derivatives, and also the method for the preparation thereof and the therapeutic or diagnostic use thereof.
Chemically Stable, Lipophilic Prodrugs of Phosphoramide Mustard as Potential Anticancer Agents
Kwon, Chul-Hoon,Moon, Ki-Young,Baturay, Nesrine,Shirota, Frances N.
, p. 588 - 592 (2007/10/02)
Benzyl phosphoramide mustard (3), 2,4-difluorobenzyl phosphoramide mustard (4), and methyl phosphoramide mustard (5) were examined as lipophilic, chemically stable prodrugs of phosphoramide mustard (2).These phosphorodiamidic esters are designed to underg
