Cancer treatment using compounds that selectively target polyploid cancer cells for disruption

A method of killing polyploid tumor cells, comprising:

• administering to a patient in need thereof, a compound of Formula I:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, and aryl;
• R2 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, alkoxy, and alkyloxyalkyl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy, esteryl, and aryl;
• R3 and R4 are each independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl, or
• R3 and R4 together form a 5 or 6-membered heteroaryl ring or a 6-membered aryl ring, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl.

A combination of therapeutic agents for use in treating a patient suffering from cancer, comprising:

• a) at least one polyploidy inducing agent for use in inducing polyploidization in one or more cancer cells in the patient;
• and
• b) a compound of Formula I:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, and aryl;
• R2 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, alkoxy, and alkyloxyalkyl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy, esteryl, and aryl;
• R3 and R4 are each independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl, or
• R3 and R4 together form a 5 or 6-membered heteroaryl ring or a 6-membered aryl ring, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl.

A method of treating a patient suffering from cancer, comprising:

• a) administering to a patient suffering from cancer a therapeutically effective amount of at least one polyploidy inducing agent, and
• b) administering to the patient a therapeutically effective amount of a compound of Formula I:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, and aryl;
• R2 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, alkoxy, and alkyloxyalkyl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy, esteryl, and aryl;
• R3 and R4 are each independently selected from hydrogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcycloalkyl, alkylcycloalkenyl, alkylcycloalkynyl, alkyloxy, alkyloxyalkyl, alkylamine, dialkylamine, arylamine, heterocyclyl, heterocyclyl, alkylheterocyclyl, aryl, alkylaryl, and heteroaryl, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl, or
• R3 and R4 together form a 5 or 6-membered heteroaryl ring or a 6-membered aryl ring, each optionally independently substituted with 1 to 6 substituents selected from hydrogen, halogen, nitro, amino, cyano, isocyano, thiol, hydroxyl, alkyl, cycloalkyl, alkoxy, aryloxy esteryl, or aryl.