In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N",N"-tri-1,2-ethanediylphosphoric triamide (TEPA) analogues
- 1 November 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (11), 2225-2230
- https://doi.org/10.1021/jm00161a016
Abstract
The nitroxyl-labeled analogues of N,N:N'',N'':N'''',N''''-tri-1,2-ethanediylphosphoric triamide (TEPA), N,N:N'',N''-bis(1,2-ethanediyl)-N''''-[[(2,2,6,6-tetramethyl-1-oxypiperidin-4-yl)amino]carbonyl]phosphoric triamide (5a) and N,N:N'',N''-bis(1,2-ethanediyl)-N''''-[[(2,2,5,5-tetramethyl-1-oxypyrrolidin-3-yl)amino]carbonyl]phosphoric triamide (11a), possess therapeutic indexes that are 8-12 times higher than those of thio-TEPA (1) and TEPA (2). The introduction of methyl groups into the aziridine ring, or the replacement of the nitroxyl moiety with hydroxylamine or amine derivatives, or with an adamantane moiety, results in compounds of lesser activity. An attempt is made to rationalize these results using a lipophilicity scale. A predictive design pattern is established.This publication has 4 references indexed in Scilit:
- In the search for new anticancer drugs. 17. Linear and cyclic polyether analogs of N,N:N',N':N",N"-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N",N"-tri-1,2-ethanediylphosphorothioic triamideJournal of Medicinal Chemistry, 1986
- Synthesis and properties of bis(2,2-dimethylaziridinyl)phosphinic amides: a series of new antineoplastic agentsJournal of Medicinal Chemistry, 1985
- In the search for new anticancer drugs. 9. Synthesis and anticancer activity of spin-labeled analogs of N,N:N',N':N",N"-tris(1,2-ethanediyl)phosphoric triamide and N,N:N',N':N",N"-tris(1,2-ethanediyl)phosphorothioic triamideJournal of Medicinal Chemistry, 1984
- One-day vath (vinblastine, adriamycin, thiotepa, and halotestin) therapy for advanced breast cancer refractory to chemotherapyCancer, 1981