Synthesis and antitumor activity of analogs of ifosfamide modified in the N-(2-chloroethyl) group
- 1 January 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (1) , 226-230
- https://doi.org/10.1021/jm00396a036
Abstract
A series of 3-(2-chloroethyl)-N-(2-X-ethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxides with various X substituents have been prepared by cyclization of racemic ifosfamide or its enantiomers with sodium hydride and subsequent treatment of intermediary products with hydrobromic acid, diethyl hydrogen phosphate, dibenzyl hydrogen phosphate, p-toluenesulfonic acid, and acetic acid. All of these compounds were tested in vivo against L 1210 lymphoid leukemia in mice. Only bromo analogue 13 and its enantiomers were effective, exceeding the activity of racemic ifosfamide and cyclophosphamide. The therapeutic index of the racemic 13 and its levorotatory enantiomer was about 1.7 times higher than that for ifosfamide and about 2.7 times higher than that for cyclophosphamide.This publication has 8 references indexed in Scilit:
- Synthesis and antitumor activity of cyclophosphamide analogs. 4. Preparation, kinetic studies, and anticancer screening of phenylketophosphamide and similar compounds related to the cyclophosphamide metabolite aldophosphamideJournal of Medicinal Chemistry, 1986
- Stereochemistry of phosphorus-nitrogen bond cleavage. First crystal and structural assignment in cyclic phosphoramidofluoridatesThe Journal of Organic Chemistry, 1985
- Activated cyclophosphamide: An enzyme-mechanism-based suicide inactivator of DNA polymerase/3??5? exonucleaseZeitschrift für Krebsforschung und Klinische Onkologie, 1984
- Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urineJournal of Medicinal Chemistry, 1983
- Phosphorus-31 NMR kinetic studies of the intra- and intermolecular alkylation chemistry of phosphoramide mustard and cognate N-phosphorylated derivatives of N,N-bis(2-chloroethyl)amineJournal of Medicinal Chemistry, 1982
- QUANTIFICATION BY GAS-CHROMATOGRAPHY OF N,N'-DI-(2-CHLOROETHYL)-PHOSPHORODIAMIDIC ACID IN THE PLASMA OF PATIENTS RECEIVING ISOPHOSPHAMIDE1980
- Synthesis and absolute configuration assignments of enantiomeric forms of ifosphamide, sulfosphamide, and trofosphamideJournal of the American Chemical Society, 1979
- Studies on cyclophosphamide metabolites and their related compounds. 8. Synthesis and antitumor activity of preactivated isophosphamide analogs bearing modified alkylating functionalitiesJournal of Medicinal Chemistry, 1978