Compounds and methods for treating cancer

A method of treating a cancer selected from ovarian cancer and pancreatic cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• the bond between X and Y is a single bond or a double bond;
• X and Y are independently selected from the group consisting of:
• O, N, CH, and C(═O);
• R1 is selected from the group consisting of:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C6-12 aryl and 5-10 membered heteroaryl, each of which is optionally substituted by 1, 2, or 3 groups independently selected from the group consisting of:
• Cy1 and Rg;
• R2 and R3 are independently selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;
• R4 is selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C6-12 aryl, and C6-12 aryl-C1-3 alkylene;
• R5A and R5B are independently selected from the group consisting of:
• H and C1-3 alkyl;
• R6A, R6B and R6C are independently selected from the group consisting of:
• OH, C1-6 alkoxy, C1-6 haloalkoxy, C(═O)NRa1Ra2, and C(O)ORa1;
• Ra1 and Ra2 are independently selected from the group consisting of:
• H and C1-3 alkyl;
• R7 is selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl, each of which is optionally substituted by 1 or 2 Cy1;
• each Cy1 is independently selected from the group consisting of:
• C6-12 aryl and 5-10 membered heteroaryl, each of which is optionally substituted by 1, 2, or 3 independently selected Rg groups;
• and
• each Rg is independently selected from the group consisting of:
• OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO—C1-3 alkyl, amino, C1-6 alkylamino and di(C1-6 alkyl)amino.

A method of inhibiting DNA polymerase θ (Polθ) in a homologous recombination (HR)-deficient cancer cell, the method comprising contacting the HR-deficient cancer cell with an effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• the bond between X and Y is a single bond or a double bond;
• X and Y are independently selected from the group consisting of:
• O, N, CH, and C(═O);
• R1 is selected from the group consisting of:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C6-12 aryl and 5-10 membered heteroaryl, each of which is optionally substituted by 1, 2, or 3 groups independently selected from the group consisting of:
• Cy1 and Rg;
• R2 and R3 are independently selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;
• R4 is selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C6-12 aryl, and C6-12 aryl-C1-3 alkylene;
• R5A and R5B are independently selected from the group consisting of:
• H and C1-3 alkyl;
• R6A, R6B and R6C are independently selected from the group consisting of:
• OH, C1-6 alkoxy, C1-6 haloalkoxy, C(═O)NRa1Ra2, and C(O)ORa1;
• Ra1 and Ra2 are independently selected from the group consisting of:
• H and C1-3 alkyl;
• R7 is selected from the group consisting of:
• H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl, each of which is optionally substituted by 1 or 2 Cy1;
• each Cy1 is independently selected from the group consisting of:
• C6-12 aryl and 5-10 membered heteroaryl, each of which is optionally substituted by 1, 2, or 3 independently selected Rg groups;
• and
• each Rg is independently selected from the group consisting of:
• OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO—C1-3 alkyl, amino, C1-6 alkylamino and di(C1-6 alkyl)amino.