Quinazolines and azaquinazolines as dual inhibitors of ras/raf/mek/erk and pi3k/akt/pten/mtor pathways

A kit comprising:

• at least one dosage form comprising a compound of formula (I):
• wherein:
• X is CH or N;
• Y is H, optionally substituted C1-C6 alkyl, OR1 or NR2R3;
• T is H or C1-C6 alkoxy;
• R1 is optionally substituted C1-C6 alkyl, optionally substituted (C1-C6 alkyl)OH, optionally substituted (C1-C6 alkyl)OC1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C6 alkyl)NH2, optionally substituted (C1-C6 alkyl)CO2H, or optionally substituted (C1-C6 alkl)CONH2;
• R2 and R3 are joined to form an optionally substituted heterocycle;
• R4 is optionally substituted morpholine;
• R6 is optionally substituted aryl or optionally substituted heteroaryl;
• R7 is optionally substituted aryl, optionally substituted C1-C6 alkyl, or optionally substituted heteroaryl;
• R8 is H or halogen;
• and
• R8′ is halogen;
• or a pharmaceutically acceptable salt thereof;
• and
• therapeutic instructions for regulating at least one of RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways, wherein the therapeutic instructions comprise the steps of:
• administering to a patient in need thereof the compound of formula (I).

A kit comprising:

• at least one dosage form comprising a compound of formula (I):
• wherein:
• X is CH or N;
• Y is H, optionally substituted C1-C6 alkyl, OR1 or NR2R3;
• T is H or C1-C6 alkoxy;
• R1 is optionally substituted C1-C6 alkyl, optionally substituted (C1-C6 alkyl)OH, optionally substituted (C1-C6 alkyl)OC1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C6 alkyl)NH2, optionally substituted (C1-C6 alkyl)CO2H, or optionally substituted (C1-C6 alkyl)CONH2;
• R2 and R3 are joined to form an optionally substituted heterocycle;
• R4 is optionally substituted morpholine;
• R6 is optionally substituted aryl or optionally substituted heteroaryl;
• R7 is optionally substituted aryl, optionally substituted C1-C6 alkyl, or optionally substituted heteroaryl;
• R8 is H or halogen;
• and
• R8′ is halogen;
• or a pharmaceutically acceptable salt thereof;
• and
• therapeutic instructions for treating cancer, wherein the therapeutic instructions comprise the steps of:
• administering to a patient in need thereof the compound of formula (I).

A method for identifying a sub-population of patients for treatment, the sub-population comprising patients with cancer or patients in need of regulation of at least one of RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways, the treatment comprising administering a therapeutically effective amount of a compound of formula (I):

• wherein:
• X is CH or N;
• Y is H, optionally substituted C1-C6 alkyl, OR1 or NR2R3;
• T is H or C1-C6 alkoxy;
• R1 is optionally substituted C1-C6 alkyl, optionally substituted (C1-C6 alkyl)OH, optionally substituted (C1-C6 alkyl)OC1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C6 alkyl)NH2, optionally substituted (C1-C6 alkyl)CO2H, or optionally substituted (C1-C6 alkyl)CONH2;
• R2 and R3 are joined to form an optionally substituted heterocycle;
• R4 is optionally substituted morpholine;
• R6 is optionally substituted aryl or optionally substituted heteroaryl;
• R7 is optionally substituted aryl, optionally substituted C1-C6 alkyl, or optionally substituted heteroaryl;
• R8 is H or halogen;
• and
• R8′ is halogen.