Synthesis and antitumor properties of some isoindolylalkylphosphonium salts.
Antitumor evaluation of 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyltriphenylphosphonium bromide (1) revealed significant activity in P-388 lymphocytic leukemia (T/C = 160%). As a follow-up to this chemical lead, a series of closely related phosphonium salts was prepared in which the 1,3-dihydro-1,3-dioxo-2H-isoindole ring system was maintained or in which it was replaced by other moieties such as maleimido, bromo, methoxy, and isoindoline. Syntheses generally involved treatment of the appropriate N-(bromoalkyl)phthalimide with the required phosphine or condensation of the K salt of the substituted imide with beta-(bromoethyl)triphenylphosphonium bromide (12). From the biological data obtained for these compounds, several requirements can be defined for substantial antileukemic activity. Of utmost importance is the presence of a triarylphosphonium halide moiety, coupled to an alkyl chain of two or three carbon atoms. The preferred terminus of the alkyl chain is the 1,3-dihydro-1,3-dioxo-2H-isoindole ring system, although the observed activity of beta-(bromoethyl)-triphenylphosphonium bromide (12) (T/C = 127%) would suggest that a superior carrier molecule could be developed.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D004353:Drug Evaluation, Preclinical; D007211:Indoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000627:therapeutic use*; D013730:Terphenyl Compounds / Q000138:chemical synthesis / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007211:Indoles; D009943:Organophosphorus Compounds; D013730:Terphenyl Compounds