Platinum compounds, compositions, and uses thereof
AssigneePlacon Therapeutics, Inc.
InventorsMark T. Bilodeau, Benoît Moreau, Adam H. Brockman, Kristan Meetze, Kerry Whalen, Richard Wooster, Rossitza G. Alargova
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Abstract
The present teachings relate to compounds and compositions for treatment of cancers. In some embodiments, the composition comprises a platinum (IV) complex having at least one reacting group for reacting with a functional group on a protein, engineered protein, antibody, antibody fragment, peptide, agonist, antagonist, aptamer or ligand which may be capable of recognizing a selected target cell population, and/or derivatives/analogs/mimics thereof.
Claims33
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X and Y are independently selected from NH, alkyl and aryl;
- R1 and R2 each is Cl, or R1 and R2 are joined to form an oxalate;
- R3 is hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of the alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups optionally is substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, wherein each of the carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl,
- R4 and R5 are each H or together constitute a cyclohexyl ring,
- Z is alternatively absent, alkyl, aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of the alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups optionally is substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, or alkylidene hydrazine wherein each of the carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl or alkylidene hydrazine is optionally substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl,
- R6 is a suitable reacting group for reacting with a functional group on a protein, engineered protein, antibody, antibody fragment, peptide, agonist, antagonist, aptamer or ligand which may be capable of recognizing a selected target cell population, and/or derivatives/analogs/mimics thereof, and wherein R6 is selected from an activated disulfide group, a vinylcarbonyl group, a vinyl acetylene group, an aziridine group, an acetylene group or any of the following groups:
- where R7 is Cl, Br, F, mesylate, tosylate, O-(4-nitrophenyl), O-pentafluorophenyl, and wherein optionally the activated disulfide group, the vinylcarbonyl group, the vinyl acetylene group, the aziridine group, the acetylene group may be substituted.
A compound selected from:
A method of synthesizing
- the method comprising:
- a. synthesizing
- from cisplatin;
- b. synthesizing
- from 6-maleimidohexanoic acid and diphenylphosphoryl azide (DPPA);
- and
- c. synthesizing compound 8 from compound 1′ and compound 2′.
Dependencies are inferred from the claim text.