In the search for new anticancer drugs. 9. Synthesis and anticancer activity of spin-labeled analogues of N,N:N',N':N",N"-Tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N",N"-tri-1,2-ethanediylphosphorothioic triamide.

Abstract

A number of N,N:N',N':N",N"-tri-1,2- ethanediylphosphoric triamide (TEPA) and N,N:N',N':N",N"-tri-1,2- ethanediylphosphorothioic triamide (thio-TEPA) derivatives containing either two aziridine moieties (1a) or two (2-chloroethyl)amino functions (1b) and either a 2,2,6,6-tetramethylpiperidine, 1-oxy-2,2,6,6-tetramethylpiperidine or 1-hydroxy-2,2,6,6-tetramethylpiperidine component were synthesized and tested against lymphocytic leukemia P388 in mice. In a structure-activity comparison it was found that at optimum dose all compounds containing the nitroxyl radical were more active than the corresponding hydroxylamine derivatives. The open-chain compounds (1b) were less active than the corresponding aziridine ring compounds (1a). The replacement of the X = bridge in 1a with the X = N(CH3) group resulted in lowering of the anticancer activity.

• Authors: G Sosnovsky, B D Paul
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 27 Issue 6 Pg. 782-8 (Jun 1984) ISSN: 0022-2623 [Print] United States
• PMID: 6204051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Azirines
• Thiotepa
• Triethylenephosphoramide

Topics

• Animals
• Antineoplastic Agents (chemical synthesis)
• Azirines (chemical synthesis)
• Leukemia P388 (drug therapy)
• Male
• Mice
• Structure-Activity Relationship
• Thiotepa (chemical synthesis, therapeutic use)
• Triethylenephosphoramide (chemical synthesis, therapeutic use)