Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues. - Archive ouverte HAL
Article Dans Une Revue Bioorganic and Medicinal Chemistry Année : 2010

Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues.

Résumé

Protein farnesyltransferase (FTase) has recently appeared as a new target of parasitic diseases, a field poor in drugs in development. With the aim of creating new bisubstrate inhibitors of FTase, new farnesyl pyrophosphate analogues have been studied. Farnesyl analogues with a malonic acid function exhibited the best inhibitory activity on FTase. This group was introduced into our imidazole-containing model leading to new compounds with submicromolar activities. Kinetic experiments have been realized to determine their binding mode to the enzyme.

Dates et versions

hal-00457520 , version 1 (17-02-2010)

Identifiants

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Stéphanie Duez, Laëtitia Coudray, Elisabeth Mouray, Philippe Grellier, Joëlle Dubois. Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues.. Bioorganic and Medicinal Chemistry, 2010, 18 (2), pp.543-56. ⟨10.1016/j.bmc.2009.12.017⟩. ⟨hal-00457520⟩
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