Cannabinoid receptor modulators

A composition comprising a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, and
• a pharmaceutically acceptable carrier.

A method for preparing a composition comprising the step of admixing a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents.

A method for preparing a composition comprising the step of admixing a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, and
• a pharmaceutically acceptable carrier.

A method for the treatment of cancer in an individual in need thereof, comprising administering to said individual, a therapeutically effective amount of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A method for the treatment of cancer in an individual in need thereof, comprising prescribing to said individual, a therapeutically effective amount of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• II, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A method for the treatment of cancer in an individual in need thereof, comprising administering to said individual, a therapeutically effective amount of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• II and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A method for the treatment of cancer in an individual in need thereof, comprising prescribing to said individual, a therapeutically effective amount of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 is absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• for use in combination with and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents.

A compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• for use in a method for the treatment of cancer in an individual in need thereof, comprising administering to said individual said compound, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 is absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• for use in a method for the treatment of cancer in an individual in need thereof, comprising prescribing to said individual said compound wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• for use in a method for the treatment of cancer in an individual in need thereof, comprising administering to said individual said compound and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• for use in a method for the treatment of cancer in an individual in need thereof, comprising prescribing to said individual said compound and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

One or more known pharmaceutical agents selected from:

• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents for use in combination with a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:
• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• II, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl.

One or more known pharmaceutical agents selected from:

• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents for use in a method for the treatment of cancer in an individual in need thereof, said method comprises administering to said individual one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents and a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:
• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 is absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

One or more known pharmaceutical agents selected from:

• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents for use in a method for the treatment of cancer in an individual in need thereof, said method comprises prescribing to said individual one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents and a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:
• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• II, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

A pharmaceutical product selected from:

• a pharmaceutical composition, a formulation, a dosage form, a combined preparation, a twin pack, and a kit;
• comprising a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:
• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• II, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents;
• for treating cancer in an individual, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

Use of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R7 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• in the manufacture of a medicament for treating cancer in an individual, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.

Use of a compound selected from compounds of Formula Ia and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

• wherein:
• R1, R2, R3, R4, R5, and R6 are each independently selected from:
• H and C1-C6 alkyl;
• X is NR7 and Y is CC(O)N(R8)R9;
• or
• X is CC(O)N(R8)R9 and Y is NR7;
• R10 is —R10—R11—R12—R13;
• wherein:
• R10 is selected from:
• C1-C6 alkylene, heteroarylene, and heterocyclylene;
• or R10 is absent;
• R11 is selected from:
• —C(O)NH— and C1-C6 alkylene;
• or R11 absent;
• R12 is C1-C6 alkylene;
• or R12 is absent;
• and
• R13 is selected from:
• C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl, aryl, and heteroaryl are each optionally substituted with one or two substituents selected from:
• C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, C1-C6 haloalkyl, halogen, and hydroxyl;
• R8 is —R14—R15—R16—R17;
• wherein:
• R14 is selected from:
• C1-C6 alkylene, C3-C7 cycloalkenylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said C1-C6 alkylene and heterocyclylene are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxycarbonyl, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, carboxy, heteroaryl, heterocyclyl, and hydroxyl;
• wherein said C1-C6 alkyl and aryl are optionally substituted with one substituent selected from:
• C1-C6 alkoxy, aryl, halogen, heteroaryl, and hydroxyl;
• or R14 is absent;
• R15 is selected from:
• —C(O)NH—, —C(O)—, —C(O)O—, C1-C6 alkylene, C3-C7 cycloalkylene, heteroarylene, and heterocyclylene;
• wherein said heterocyclylene is optionally substituted with C1-C6 alkyl;
• or R15 is absent;
• R16 is C1-C6 alkylene;
• or R16 is absent;
• and
• R17 is selected from:
• H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C2-C6 alkynyl, ureyl, amino, aryl, arylamino, arylcarbonyl, aryloxy, carbo-C1-C6-alkoxy, carboxamide, carboxy, cyano, C3-C7 cycloalkyl, C5-C11 bicycloalkyl, C3-C7 cycloalkylamino, C2-C8 dialkylamino, C2-C8 dialkylsulfonamide, C1-C6 haloalkyl, heteroaryl, heteroaryloxy, heterobicyclyl, heterocyclyl, hydroxyl, and phosphonooxy;
• wherein said C1-C6 alkylamino, amino, aryl, arylamino, aryloxy, C5-C11 bicycloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylamino, heteroaryl, heterobicyclyl, heterocyclyl, and ureyl are each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylsulfonyl, amino, aryl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl;
• and
• R9 is selected from:
• H, C1-C6 alkyl, and C3-C7 cycloalkyl;
• or
• R8 and R9 together with the nitrogen atom to which they are both bonded form a group selected from:
• heterocyclyl and heterobicyclyl, each optionally substituted with one or more substituents selected from:
• Carbo-C1-C6-alkoxy, C1-C6 alkoxy, C1-C6 alkyl, aryl, carbo-C1-C6-alkoxy, C1-C6 haloalkyl, halogen, heteroaryl, heteroaryloxy, heterocyclyl, and hydroxyl;
• wherein said aryl, C1-C6 alkyl, and heteroaryl are optionally substituted with one substituent selected from:
• C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, and hydroxyl,
• and one or more known pharmaceutical agents selected from:
• inhibitors of inherent multidrug resistance, anti-emetic agents, agents useful in the treatment of anemia, agents useful in the treatment of neutropenia, immunologic-enhancing agents, and anticancer agents in the manufacture of a medicament for treating cancer in an individual, wherein the cancer is not prostate cancer, leukemia, lymphoma, or a CNS tumor.