Peter Ten Holte

Synthesis of 3-Amino-4-fluoropyrazoles

Fluorinated pyrazoles bearing additional functional groups that allow further functionalization are of considerable interest as building blocks in medicinal chemistry. The developed synthetic strategy for new 3-amino-4-fluoropyrazoles consists of a monofluorination of β-methylthio-β-enaminoketones using 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) toward the corresponding monofluorinated enaminoketones, followed by condensation with different hydrazines.

Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors

Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.