Methods of Treating Cancer Using Pyridopyrimidinone Inhibitors of PI3K and mTOR in Combination with Autophagy Inhibitors

A method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I:

• or a single isomer thereof where the compound is optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof;
• or
• administering a pharmaceutical composition comprising a therapeutically effective amount of a Compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent in combination with one or more autophagy inhibitors, wherein in the Compound of Formula I;
• R1 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
• R2 is hydrogen or alkyl where the alkyl is optionally substituted with 1, 2, 3, 4, or 5 R8 groups;
• X is —NR3—
• R3 hydrogen;
• R4 is optionally substituted alkyl;
• R5 is hydrogen;
• and
• R6 is phenyl, acyl, or heteroaryl wherein the phenyl and heteroaryl are optionally substituted with 1, 2, 3, 4, or 5 R9 groups;
• each R8, when present, is independently hydroxy, halo, alkoxy, haloalkoxy, amino, alkylamino, dialkylaminoalkyl, or alkoxyalkylamino;
• and
• each R9, when present, is independently halo, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkoxyalkyl, carboxyalkyl, alkoxycarbonyl, aminoalkyl, cycloalkyl, aryl, arylalkyl, aryloxy, heterocycloalkyl, or heteroaryl and where the cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each either alone or as part of another group within R9, are independently optionally substituted with 1, 2, 3, or 4 groups selected from halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkxy, amino, alkylamino, and dialkylamino.