221679-69-2Relevant articles and documents
Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids
Ambro?ak, Agnieszka,Steinebach, Christian,Gardner, Erin R.,Beedie, Shaunna L.,Schnakenburg, Gregor,Figg, William D.,Gütschow, Michael
, p. 2621 - 2629 (2016/12/09)
The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses.
A new one-pot synthesis of 5,5-disubstituted hydantoins from diethyl acetamidomalonates and ureas
Guetschow, Michael,Hecker, Thomas,Eger, Kurt
, p. 410 - 414 (2007/10/03)
A new one-pot synthesis of 5,5-disubstituted hydantoins 3 is reported. Diethyl 2-acetamido-2-alkylmalonates were found to react with substituted ureas in the presence of sodium ethoxide to produce the 5-alkyl-5- carbamoylhydantoins 3 a-e. The reaction involves a ring contraction of intermediate 5-aminobarbituric acids to the final hydantoin derivatives. The 5-aminobarbituric acids 2 d-f were prepared from azido derivatives 6 d-f. On treatment with sodium ethoxide, 2 d-f underwent the rearrangement to afford the hydantoins 3 d-f.
