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2005
Enzyme inhibiting activity
X 0220
Phosphonomethylphosphorylmethyl(oxy)-Analogues of Geranylgeranyl Diphosas Stable and Selective Geranylgeranyl Protein Transferase Inhibitors. —
15- 240 phate
The polar portion of geranylgeranyl diphosphate (GGdP) is replaced with diphosphonate groups mimicking the native diphosphate unit. GGdP-Analogues (I) are metabolically stable towards phosphoesterase enzymes. Compounds with a methylene linker
show poor [(Ia), (Ib)] to significant [(Ic)] activity on GGTase. When an oxygen atom is
interposed between the polar portion and the side chain, the GGTase inhibition is improved considerably. Moreover, compound (Id) still possesses an appreciable
GGTase/FTase selectivity ratio. — (MACCHIA*, M.; et al.; Farmaco 59 (2004) 11,
887-892; Dip. Sci. Farm., Univ. Pisa, I-56126 Pisa, Italy; Eng.) — H. Hoennerscheid
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