Synthesis and antitumor activity of simple vinyl and alpha-methylene-gamma-butyrolactone sulfonate esters and silyl enol ethers.
A number of simple silyl enol ethers and vinyl trifluoromethanesulfonates, a relatively new class of organic compounds capable of undergoing alkylation by a nucleophilic addition-elimination process, were evaluated in the P388 lymphocytic leukemia system. No activity (ILS = 8-22%) was observed in the simple vinyl derivatives. Some activity (ILS = 20-42%) was observed for a series of siloxy and sulfonate (CH3SO2 and CF3SO3) functionalized alpha-methylene lactone systems. The enhanced activity of the functionalized systems over the parent methylene lactone is ascribed to a possible irreversible alkylation by cellular nucleophiles via a nucleophilic addition-elimination process.
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000477:Alkylating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis*; D007942:Leukemia, Experimental / Q000188:drug therapy; D008698:Mesylates / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D005663:Furans; D008698:Mesylates; D014753:Vinyl Compounds; D015107:4-Butyrolactone