O,O'-amidomalonate and N,O-amidomalonate platinum complexes
AssigneeAccess Pharmaceuticals, Inc.
InventorsPaul Sood, Donald R. Stewart, David P. Nowotnik, Sergiy Victorovych Schevchuk, Kenneth Bruce Thurmond II
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Abstract
The present invention relates to amidomalonate O,O′—Pt and N,O—Pt chelates and methods of preparing them in essentially pure form.
Claims47
An amidomalonate N,O—Pt complex having the chemical structure:
- 6
- wherein:
- X is C═O or SO2;
- R1 is selected from the group consisting of hydrogen, an aliphatic group, a water-solubilizing group, a tumor-targeting group and a water-solubilizing group further comprising one or more tumor-targeting group(s);
- q is 0 or 1;
- r is 1-500;
- [Linker] is selected from the group consisting of an alkyl group, an amino acid, a polyaminoacid, a polyethyleneglycol (PEG) and any combination of thereof;
- R2 and R3 are independently selected from the group consisting of NH3, a primary amine, a secondary amine, a tertiary amine and a nitrogen-containing heteroalicyclic;
- or,
- R2 and R3 are independently primary, secondary or tertiary amino groups, both of which are covalently bonded to carbon atoms of an aliphatic, an alicyclic, an aromatic, an aralkyl or a heterocyclic group wherein, when the amino group nitrogen atoms form a chelate with the Pt atom, a 5-7 member ring results;
- R4 is selected from the group consisting of hydrogen, a cation and an ester-forming group, wherein,
- the complex is obtained essentially pure by a process comprising contacting a corresponding amidomalonate O,O′—Pt complex or a mixture of amidomalonate O,O′—Pt and N,O—Pt complexes with an aqueous solution having a pH of 6.0 to 10.0.
An amidomalonate O,O′—Pt complex having the chemical structure:
- 7
- wherein:
- X is C═O or SO2;
- R1 is selected from the groups consisting of hydrogen, an aliphatic group, a water-solubilizing group, a tumor-targeting group and a water-solubilizing group further comprising one or more tumor-targeting group(s);
- q is 0 or 1;
- r is 1-500;
- [Linker] is selected from the group consisting of an alkyl group, an amino acid, a polyaminoacid, a polyethylene glycol (PEG) and any combination of thereof;
- R2 and R3 are independently selected from the group consisting of NH3, a primary amine, a secondary amine, a tertiary amine and a nitrogen-containing heterocyclic;
- or,
- R2 and R3 are independently primary, secondary or tertiary amino groups, both of which are covalently bonded to carbon atoms of an aliphatic, an alicyclic, an aromatic, an alkaryl or a heterocyclic group wherein, when the amino nitrogen atoms form a chelate with the Pt atom, a 5-7 member ring results;
- the complex is obtained essentially pure by a process comprising contacting a corresponding amidomalonate N,O′—Pt complex or a mixture of amidomalonate N,O—Pt and O,O′—Pt complexes with an aqueous solution having a pH of 3.5 or less.
A method of preparing an essentially pure amidomalonate N,O—Pt chelate from an essentially pure amidomalonate O,O′—Pt chelate or a mixture of amidomalonate N,O—Pt and O,O′—Pt chelates, comprising contacting the amidomalonate O,O′—Pt chelate or the mixture of amidomalonate N,O—Pt and O,O′—Pt chelates with an aqueous solution having a pH of 6.0-10.0.
A method of preparing an essentially pure amidomalonate O,O′—Pt chelate from an essentially pure amidomalonate N,O—Pt chelate or a mixture of amidomalonate N,O—Pt and O,O′—Pt chelates, comprising contacting the amidomalonate N,O—Pt chelate or the mixture of amidomalonate N,O—Pt and O,O′—Pt chelates with an aqueous solution having a pH of 3.5 and lower.
Dependencies are inferred from the claim text.