Other

Ivax International Gmbh

Chemgenex Pharmaceuticals, Inc.

Robin, Jean-pierre

Radosevic, Nina

Blanchard, Julie

Roisnel, Thierry

Bataille, Thierry

Julie Blanchard

Jean-Pierre Robin

Nina Radosevic

Jean-Pierre Marie

Thierry Roisnel

Thierry Bataille

François-Xavier Mahon

Frederick Maloisel

Hervé Maissonneuve

The present disclosure concerns harringtonines salts at the crystalline state exhibiting a protonated nitrogen seen in solid state analysis and having general formula 1,  in which R1 is, but not limited to, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl or heterocycloalkyl, and R2 is, independently, but not limited to H, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl or heterocycloalkyl, with an acid having general formula AH in a non-aqueous crystallization solvent, wherein the said salt has a large water solubility. The disclosure is also related to a process for preparing and purifying these salts and their use as chemotherapeutic drugs.

Harringtonines salts in the crystalline state and their use for the purification of the corresponding drug substance

The present invention concerns a new general process for asymmetric hemisynthesis of harringtonines and their analogs, that are alkaloids used in chemotherapy. This process comprises direct esterification of a natural cephalotaxine with an acylating compound constituted of a side chain precursor which backbone and functionalization are entirely preformed. The invention also concerns a natural, synthetic or semi-synthetic harringtonines including their tautomeric forms and their salts of the following formula: wherein n=2 (i.e. harringtonine) or n=3 (i.e. homoharringtonine),in which the total content of impurities, possibly including enantiomeric forms, is lower than 1%, and/or the content of the major impurity is lower than 0.9%, and/or the chromatographic assay exhibits a harringtonines content higher than 97.5%.

Cephalotaxane derivatives and their processes of preparation and purification

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Puyricard, France

Julie Blanchard