Substituted bicyclic and tricyclic ureas and amides, analogues thereof, and methods using same

A compound of formula (I), or a salt, solvate, prodrug, stereoisomer, tautomer, or isotopically labelled derivative thereof, or any mixtures thereof:

• wherein:
• X, Y, and the bond between X and Y are such that:
• X is NR7, Y is C(═O), and the bond between X and Y is a single bond, or
• X is N, Y is CR10, and the bond between X and Y is a double bond;
• A ring
• is selected from the group consisting of:
• wherein there is no bridgehead double bond),
• wherein:
• in (Ai) R8a and R8b optionally combine with the carbon atom to which they are attached to form carbonyl (—(C═O)—);
• in (Aii) R8a and R8b, or R8c and R8d, optionally combine with the carbon atom to which they are attached to form carbonyl (—(C═O)—);
• in (Aiii) R8c and R8d, or R8e and R8f, optionally combine with the carbon atom to which they are attached to form carbonyl (—(C═O)—);
• in (Aiv) R8e and R8f optionally combine with the carbon atom to which they are attached to form carbonyl (—(C═O)—);
• or the A ring is absent, position 3 of the pyridin-2-one ring is substituted with R8a, and position 4 of the pyridin-2-one ring is substituted with R8b;
• R1 is —NR2R3 or optionally substituted isoindolin-2-yl;
• R2 is selected from the group consisting of optionally substituted C3-C8 cycloalkyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted heteroaryl, and —(CH2)(optionally substituted heteroaryl);
• R3 is selected from the group consisting of H and C1-C6 alkyl;
• R4 is selected from the group consisting of H, C1-C6 alkyl, and C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted with at least one selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halogen, cyano, —OH, C1-C6 alkoxy, C3-C8 cycloalkoxy, C1-C6 haloalkoxy, C3-C8 halocycloalkoxy, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —C(═O)OR9, —OC(═O)R9, —SR9, —S(═O)R9, —S(═O)2R9, —S(═O)2NR9R9, —N(R9)S(═O)2R9, —N(R9)C(═O)R9, —C(═O)NR9R9, and —NR9R9;
• R5 is selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• R6 is —(CH2)p-Q-(CH2)q—,
• wherein p and q are independently 0, 1, 2, or 3, and
• Q is a bond (absent), —O—, —OCH(OH)—, —CH(OH)O—, —S—, —S(═O)—, —S(═O)2—, —NR11, —CH(OH)—, —C(═O)—, —C(═O)O—, or —OC(═O)—,
• wherein p and q are selected such that:
• 2≤(p+q)≤4 if Q is a bond,
• 1≤(p+q)≤3 if Q is —O—, S—, —S(═O)—, —S(═O)2—, —NR11, —CH(OH)—, or —C(═O)—,
• 0≤(p+q)≤2 if Q is —C(═O)O—, —OC(═O)—, —OCH(OH)—, or —CH(OH)O—, and
• wherein each CH2 is optionally independently substituted with one or two methyl groups;
• R7 is selected from the group consisting of H, optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl;
• each occurrence of R8a, R8b, R8c, R8d, R8e, R8f, R8g, and R8h is independently selected from the group consisting of H, halogen, cyano, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C3-C8 cycloalkoxy, heterocyclyl, heteroaryl, —S(optionally substituted C1-C6 alkyl), —SO(optionally substituted C1-C6 alkyl), —SO2(optionally substituted C1-C6 alkoxy), —C(═O)OH, —C(═O)O(optionally substituted C1-C6 alkyl), —C(═O)O(optionally substituted C3-C8 cycloalkyl), —O(optionally substituted C1-C6 alkyl), —O(optionally substituted C3-C8 cycloalkyl), —NH2, —NH(optionally substituted C1-C6 alkyl), —NH(optionally substituted C3-C8 cycloalkyl), —N(optionally substituted C1-C6 alkyl)(optionally substituted C1-C6 alkyl), —N(optionally substituted C3-C8 cycloalkyl)(optionally substituted C3-C8 cycloalkyl), —N(optionally substituted C1-C6 alkyl)(optionally substituted C3-C8 cycloalkyl), —C(═O)NH2, —C(═O)NH(optionally substituted C1-C6 alkyl), —C(═O)NH(optionally substituted C3-C8 cycloalkyl), —C(═O)N(optionally substituted C1-C6 alkyl)(optionally substituted C1-C6 alkyl), —C(═O)N(optionally substituted C3-C8 cycloalkyl)(optionally substituted C3-C8 cycloalkyl), and —C(═O)N(optionally substituted C1-C6 alkyl)(optionally substituted C3-C8 cycloalkyl;
• each occurrence of R9 is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted phenyl, and optionally substituted hetereoaryl;
• R10 is selected from the group consisting of H, halogen, cyano, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C3-C8 cycloalkoxy, heterocyclyl, heteroaryl, —S(optionally substituted C1-C6 alkyl), —SO(optionally substituted C1-C6 alkyl), —SO2(optionally substituted C1-C6 alkyl), —C(═O)OH, —C(═O)O(optionally substituted C1-C6 alkyl), —C(═O)O(optionally substituted C3-C8 cycloalkyl), —O(optionally substituted C1-C6 alkyl), —O(optionally substituted C3-C8 cycloalkyl), —NH2, —NH(optionally substituted C1-C6 alkyl), —NH(optionally substituted C3-C8 cycloalkyl), —N(optionally substituted C1-C6 alkyl)(optionally substituted C1-C6 alkyl), —N(optionally substituted C3-C8 cycloalkyl)(optionally substituted C3-C8 cycloalkyl), —N(optionally substituted C1-C6 alkyl)(optionally substituted C3-C8 cycloalkyl), —C(═O)NH2, —C(═O)NH(optionally substituted C1-C6 alkyl), —C(═O)NH(optionally substituted C3-C8 cycloalkyl), —C(═O)N(optionally substituted C1-C6 alkyl)(optionally substituted C1-C6 alkyl), —C(═O)N(optionally substituted C3-C8 cycloalkyl)(optionally substituted C3-C8 cycloalkyl), and —C(═O)N(optionally substituted C1-C6 alkyl)(optionally substituted C3-C8 cycloalkyl;
• and
• R11 is selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, and optionally substituted C1-C6 acyl.