EBNA1 Inhibitors and Methods Using Same

A compound of formula (I), or an enantiomer, diastereomer, tautomer, salt or solvate thereof:

• wherein:
• X1 is selected from the group consisting of CR4a and N;
• X2 is selected from the group consisting of CR4b and N;
• X3 is selected from the group consisting of CR4c and N;
• R1 is selected from the group consisting of
• R2 is selected from the group consisting of
• R3 is selected from the group consisting of —CO2R4d, —C(═O)NH—S(═O)2NR5R6, —S(═O)2NHC(═O)R7, —NHS(═O)2R7, and 1H-tetrazol-5-yl;
• R4a, R4b, and R4c are each independently selected from the group consisting of F, Cl, Br, I, and H;
• R4d is selected from the group consisting of H, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
• R5 is selected from the group consisting of H, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
• R6 is selected from the group consisting of H, optionally substituted C1-6 linear alkyl, and optionally substituted C3-6 branched alkyl;
• or R5 and R6 are taken together with the atoms to which they are connected to form a 3-, 4-, 5-, or 6-membered ring optionally containing a unit selected from the group consisting of oxygen, sulfur, SO, SO2, CF2, NH, N(C1-6 alkyl), N(C3-7 branched alkyl), N(C3-6 cycloalkyl), N(heteroaryl), NCO(C1-6 alkyl), NCO(C1-6 branched alkyl), NCO(C3-6 cycloalkyl), NCO2(C1-6 alkyl), NCO2(C1-6 branched alkyl), NCO2(C3-6 cycloalkyl), NCON(C1-6 alkyl)2, SO2NH2, NSO2(C1-6 alkyl), NSO2(C3-6 branched alkyl), NSO2(C3-6 cycloalkyl), and NSO2Aryl;
• R7 is selected from the group consisting of H, optionally substituted C1-6 linear alkyl, optionally substituted C3-6 branched alkyl, C1-6 haloalkyl, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted heteroaryl, and —CH(R5)(R6);
• R8a, R8b, R8c, R8d, and R8e are each independently selected from the group consisting of H, halogen, hydroxyl, CN, optionally substituted C1-6 linear alkyl, optionally substituted C3-6 branched alkyl, and C1-6 alkoxy;
• R9a, R9b, R9c, R9d, and R9e are each independently selected from the group consisting of H, halogen, optionally substituted C1-6 linear alkyl, C1-6 alkoxy, and optionally substituted C3-6 branched alkyl;
• R10a and R10b are each independently selected from the group consisting of H, optionally substituted C1-6 linear alkyl, and optionally substituted C1-6 branched alkyl;
• L1 is selected from the group consisting of —C≡C—, —CH═CH— and —(CH2)n—;
• L2 is selected from a group consisting of NH, (CH2)m, and
• wherein “**” indicates the point of attachment for R2;
• Q1 is selected from a group consisting of optionally substituted benzyl, —COR7, —SO2R7,
• n is 0, 1, 2, or 3;
• m is 0, 1, 2, or 3;
• q is 1, 2, 3, or 4;
• and
• x is 0, 1, 2, or 3.