Combretastatin A-3 prodrug

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...

Reexamination Certificate

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C558S156000

Reexamination Certificate

active

07547686

ABSTRACT:
A new and more efficient synthesis of combretastatin A-3 (2a) was completed (8.4% overall yield) starting from methyl gallate and isovanillin with aldehyde 5 and phosphonium salt 8 as key intermediates. Conversion of combretastatin A-3 (2a) to a series of diphosphate prodrugs (lOa-lOl) containing selected anions was achieved. Both the diphosphate sodium (lOa) and potassium salts (lOc) displayed aqueous solubility in excess of 220 mg/ml at room temperature and good cancer cell line inhibitory activity.

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Office Action dated Aug. 18, 2008 for corresponding EP application No. 02 746 550.9 (5 sheets).

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