Inhibitors of RAD52 Recombination Protein and Methods Using Same

A method of treating or ameliorating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, solvate, tautomer, enantiomer, diastereomer, or N-oxide thereof:

• wherein in (I):
• X at position 1 and X at position 3 are N, or X at position 1 is CH and X at position 3 is CH or N;
• R1 is selected from the group consisting of:
• Y is O or S;
• R2 is —NR4R5,
• with the proviso that, if R1 is
• then R2 is
• R3 is selected from the group consisting of hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C1-C6)heteroalkyl, —F, —Cl, —Br, —I, —CN, —NO2, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —C(═O)R7, —OC(═O)R7, and —CO2R7;
• each occurrence of R4 and R5 is independently selected from the group consisting of hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C1-C6)heteroalkyl, aryl, and heteroaryl, wherein the aryl or heteroaryl group is optionally substituted;
• or R4 and R5 in R1, together with the nitrogen to which R4 and R5 are connected,
• form a 3-10 membered heterocycloalkyl,
• each occurrence of R6 is independently selected from the group consisting of -(C1-C6)alkyl, -(C1-C6)heteroalkyl, —OR7, 3-10 membered heterocycloalkyl, aryl, and heteroaryl, wherein the 3-10 membered heterocycloalkyl, aryl or heteroaryl group is optionally substituted;
• each occurrence of R7 is independently selected from the group consisting of H, -(C1-C6)alkyl, -(C1-C6)heteroalkyl, -(C3-C6)cycloalkyl, -4-10 membered heterocycloalkyl, aryl, and -(C5-C10)heteroaryl, wherein the alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl group is optionally substituted.

A method of preventing or treating a RAD52 related disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, solvate, tautomer, enantiomer, diastereomer, or N-oxide thereof:

• wherein in (I):
• X at position 1 and X at position 3 are N or X at position 1 is CH and X at position 3 is CH or N;
• Y is O or S;
• R1 is selected from the group consisting of:
• R1 is selected from the group consisting of:
• R2 is —NR4R5,
• with the proviso that, if R1 is
• then R2 is
• R3 is selected from the group consisting of hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C1-C6)heteroalkyl, —F, —Cl, —Br, —I, —CN, —NO2, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —C(═O)R7, —OC(═O)R7, and —CO2R7;
• each occurrence of R4 and R5 is independently selected from the group consisting of hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C1-C6)heteroalkyl, aryl, and heteroaryl, wherein the aryl or heteroaryl group is optionally substituted;
• or R4 and R5 in R1, together with the nitrogen to which R4 and R5 are connected, form a 3-10 membered heterocycloalkyl,
• each occurrence of R6 is independently selected from the group consisting of -(C1-C6)alkyl, -(C1-C6)heteroalkyl, —OR7, 3-10 membered heterocycloalkyl, aryl, and heteroaryl, wherein the 3-10 membered heterocycloalkyl, aryl or heteroaryl group is optionally substituted;
• each occurrence of R7 is independently selected from the group consisting of H, -(C1-C6)alkyl, -(C1-C6)heteroalkyl, -(C3-C6)cycloalkyl, -4-10 membered heterocycloalkyl, aryl, and -(C5-C10)heteroaryl, wherein the alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl group is optionally substituted.