Salts of conjugates for cancer therapy
AssigneeBiosight Ltd.
InventorStela Gengrinovitch
Life of this patent
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Abstract
The present invention relates to pharmaceutically acceptable salts of conjugates comprising a chemotherapeutic drug and an amino acid or a derivative thereof, which are readily taken up by a target cell and reduce side effects induced by the chemotherapeutic drug. In particular, the present invention relates to pharmaceutically acceptable salts of conjugates comprising cytidine analog drugs and aspartic or glutamic acid and analogs thereof, pharmaceutical compositions comprising these conjugates and use thereof for the treatment of cancer or a pre-cancer condition or disorder.
Claims6
A process for preparing a compound of formula (1) comprising the step of:
- (a) coupling a compound of formula (i) with a drug of formula D or a protected derivative thereof of formula D-(P3)n in the presence of a coupling reagent to afford an intermediate of formula (ii), wherein D is cytarabine or a residue thereof, and wherein the cytarabine is attached to the C═O group via its amine group;
- and
- (b) removing the protecting groups P1, P2 and removing P3 if present, with a strong acid (Y) or with a deprotecting agent followed by a strong acid (Y) so as to generate a salt represented by the formula (1):
- wherein P1 is a carboxy protecting group, P2 is an amino protecting group, P3 is a protecting group located on one or more functional groups on the drug D, n is 0, 1, 2 or 3;
- and Y is a strong acid.
A process for preparing a compound of formula (1)
- wherein Y is a pharmaceutically acceptable organic or inorganic strong acid or a residue thereof,
- wherein the process comprises:
- (a) protecting 5′ OH on the arabinose sugar of cytarabine structure to obtain at least one compound 20a, 20b, 20c, 20d or combination thereof:
- wherein P3 is a protecting group and X is a leaving group;
- (b) coupling compound 20a, 20b, 20c, 20d or combination thereof with compound 21 in the presence of a coupling reagent to afford accordingly compound 22a, 22b, 22c, 22d or combination thereof:
- wherein P1 is a carboxy protecting group, P2 is an amino protecting group, P3 is a protecting group;
- and
- (c) removing the protecting groups P1, P2 and P3, with a strong acid (Y) or with a deprotecting agent followed by a strong acid (Y) so as to generate a salt represented by the formula (1).
Dependencies are inferred from the claim text.