title: 4-Methylideneisoxazolidin-5-ones--a new class of alpha-methylidene-gamma-lactones with high cytostatic activity.
abstract: A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC(50)<1 microM. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC(50) values of 0.74 and 0.34 microM, respectively.
authors.affiliation: Institute of Organic Chemistry, Technical University of Łódź, 90-924 Łódź, Poland. tjanecki@p.lodz.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janecki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wasek
authors.forename: Marek
authors.initials: M
authors.lastname: Rózalski
authors.forename: Urszula
authors.initials: U
authors.lastname: Krajewska
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Studzian
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D010080:Oxazoles