Tetrahydronaphthyridine and related bicyclic compounds for inhibition of RORgamma activity and the treatment of disease

A compound represented by Formula I:

• or a pharmaceutically acceptable salt or solvate thereof;
• wherein:
• A is aryl, aralkyl, heteroaryl, cycloalkyl, or heterocycloalkyl;
• each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxy, C1-6haloalkoxy, —N(R4)(R5), —CO2R6, —C(O)R6, —CN, —C1-4alkylene-C1-4alkoxy, —C1-4alkylene-N(R4)(R5), —C1-4alkylene-CO2R6, —O—C1-6alkylene-N(R4)(R5), —N(R4)C(O)—C1-6alkylene-N(R4)(R5), —S(O)pC1-6alkyl, —SO2N(R4)(R5), —N(R4)SO2(C1-6alkyl), —C(O)N(R4)(R5), and —N(R4)C(O)N(R4)(R5);
• X is —O—[C(R6)(R7)]—[C(R6)2]m-ψ, —O—C(R6)2—C(R6)(R7)—C(R6)2-ψ, —O—C(R6)2—C(R6)(R7)—ψ, —C(R6)2—[C(R6)(R7)]—[C(R6)2]m-ψ, —C(O)—[C(R6)(R7)]—[C(R6)2]m-ψ, —C(R6)2—N(R8)—[C(R6)(R7)]—[C(R6)2]m-ψ, —C(R6)═N-ψ, —C(R6)2C(R6)═N-ψ, —N═C(R6)—ψ, or —N═C(R6)C(R6)2- ψ;
• wherein ψ is a bond to the sulfonamide ring nitrogen atom in Formula I;
• Y1 is C(R3), and Y2 is N;
• R1 is hydrogen or C1-6alkyl;
• R2 is hydrogen, —C(O)-aryl, —C(O)-aralkyl, —C(O)—[C(R6)2]m-cycloalkyl, —C(O)—[C(R6)2]m-heterocyclyl, —C(O)—C1-8alkyl, —C(O)—C1-6alkylene-C1-6alkoxyl, —C(O)—C1-6alkylene-cycloalkyl, or —C(O)—C1-6alkylene-heterocycloalkyl;
• each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, C1-6alkoxy, C1-6haloalkoxy, C1-6alkyl, C1-6haloalkyl, —N(R4)(R5), —CN, —CO2—C1-6alkyl, —C(O)—C1-6alkyl, —C(O)N(R4)(R5), —S(O)pC1-6alkyl, —SO2N(R4)(R5), and —N(R4)SO2(C1-6alkyl);
• R3 represents independently for each occurrence hydrogen, halogen, or C1-6alkyl;
• R4 and R5 each represent independently for each occurrence hydrogen or C1-6alkyl;
• or R4 and R5 taken together with the nitrogen atom to which they are attached form a 3-7 membered heterocyclic ring;
• R6 represents independently for each occurrence hydrogen or C1-6alkyl;
• R7 is hydrogen, hydroxyl, C1-6hydroxyalkyl, C1-6alkyl, C1-6haloalkyl, —CO2R6, C1-6alkylene-CO2R6, C1-4hydroxyalkylene-CO2R6, —N(R4)(R5), C1-6alkylene-N(R4)(R5), C1-6hydroxyalkylene-N(R4)(R5), —N(R4)C(O)R9, C1-6alkylene-N(R4)C(O)R9, C1-6alkylene-C(O)N(R4)(R5), —N(R4)CO2—C1-6alkyl, or C1-6alkylene-N(R4)C(O)N(R4)(R5);
• or R7 is heterocycloalkyl or C1-4alkylene-heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of oxo, halogen, hydroxyl, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxy, and C1-6haloalkoxy;
• R8 is hydrogen, C1-6alkyl, or —C(O)—C1-6alkyl;
• R9 is hydrogen, C1-6alkyl, C1-6hydroxyalkyl, —N(R4)(R5), C1-6alkylene-N(R4)(R5), or C1-6alkylene-N(R4)C(O)—C1-6alkyl;
• each of which is optionally substituted with 1, 2, or 3 halogen, hydroxyl or amino, and
• m and p each represent independently for each occurrence 0, 1, or 2.