Methods of using 4(1H)-quinolone derivatives

A method of treating one or more cancers of lung cancer, breast cancer, ovarian cancer, prostate cancer, colon cancer, head cancer, neck cancer, head and neck cancer and leukemia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formulae (IA), (IB), or (IC):

• or a pharmaceutically acceptable salt, co-crystal, tautomer, or stereoisomer thereof, wherein:
• each instance of R1 is independently halogen, —C(═O)(-unsubstituted alkyl), unsubstituted or substituted alkyl by halogen, unsubstituted or substituted alkenyl by halogen, unsubstituted or substituted alkynyl by halogen, unsubstituted or substituted carbocyclyl by halogen, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• R2 of the formula (IA) is independently —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═O)(OCH2CH2)zOR2c, —(CH2)xORaa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, or —N(RD1a)2;
• R2 of the formula (IB) is independently halogen, —C(═O)Raa—CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═O)(OCH2CH2)zOR2c, —(CH2)xORaa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, —C(═NR bb)Raa—C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, -unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• and R2 of the formula (IC) is independently halogen, —C(═O)OR2a, —C(═O)N(Rbb)2, —C(═O)(OCH2CH2)zOR2c, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, —(CH2)xORaa, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• R3 is hydrogen, unsubstituted alkyl, or a nitrogen protecting group;
• each instance of R4 is independently halogen, —C(═O)Raa—CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• RD1 is hydrogen, —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, —C(═S)N(Rbb)2, —C(═O)SRaa, C(═S)SRaa, unsubstituted alkyl, unsubstituted alkenyl, -unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;
• each occurrence of RD1a is hydrogen, —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or a nitrogen protecting group;
• or two instances of RD1a are taken together with their intervening atoms to form an unsubstituted heterocyclic or unsubstituted heteroaryl ring;
• R2a is unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom;
• Raa is hydrogen, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom;
• each occurrence of Rbb is hydrogen, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or a nitrogen protecting group when attached to a nitrogen atom;
• R2c is hydrogen;
• m is 0, 1, 2, 3, 4, or 5;
• x is 1, 2, 3, 4, 5, or 6;
• z is 1, 2, 3, 4, 5, or 6;
• and
• p is 0 or 1.

A method of treating leukemia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA)

• or a pharmaceutically acceptable salt, co-crystal, tautomer, or stereoisomer thereof, wherein:
• each instance of R1 is independently halogen, —C(═O)(-unsubstituted alkyl), unsubstituted or substituted alkyl by halogen, unsubstituted or substituted alkenyl by halogen, unsubstituted or substituted alkynyl by halogen, unsubstituted or substituted carbocyclyl by halogen, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• R2 is independently halogen, —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═O)(OCH2CH2)zOR2c, —(CH2)xORaa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, —C(═NRbb) Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• R3 is hydrogen, unsubstituted alkyl, or a nitrogen protecting group;
• each instance of R4 is independently halogen, —C(═O)Raa—CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, —CN, —ORD1, —N(RD1a)2, or —SRD1;
• RD1 is hydrogen, —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;
• each instance of RD1a is hydrogen, —C(═O)Raa, —CHO, —CO2Raa, —C(═O)N(Rbb)2, —C(═NRbb)Raa, —C(═NRbb)ORaa, —C(═NRbb)N(Rbb)2, —C(═O)NRbbSO2Raa, —C(═S)N(Rbb)2, —C(═O)SRaa, —C(═S)SRaa unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or a nitrogen protecting group;
• or two instances of RD1a are taken together with their intervening atoms to form an unsubstituted heterocyclic or unsubstituted heteroaryl ring;
• Raa is hydrogen, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom;
• each occurrence of Rbb is hydrogen, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted heteroaryl, or a nitrogen protecting group when attached to a nitrogen atom;
• R2c is hydrogen;
• m is 0, 1, 2, 3, 4, or 5;
• x is 1, 2, 3, 4, 5, or 6;
• z is 1, 2, 3, 4, 5, or 6;
• and
• p is 0 or 1.