In the search for new anticancer drugs. 17. Linear and cyclic polyether 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.
Linear and cyclic polyether derivatives 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) are synthesized and evaluated for their antineoplastic activity against the murine lymphocytic leukemia P388. All compounds, except for 7d, were active ranging from 42% to 287% increase in life span (% ILS). All CD2F1 male mice treated with the most active compound (7a) at 90 mg/kg per day for 9 days were alive after 30 days, whereas all mice treated with the clinical drug thio-TEPA were dead. The % ILS for compound 7a on day 60 was 525. A correlation is presented between the structural features of compounds and their lipophilicities and antineoplastic activities.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007202:Indicators and Reagents