Diazanaphthalen-3-yl carboxamides and preparation and use thereof

A compound, or a pharmaceutically acceptable salt thereof, of Formula I:

• wherein:
• R1, R2, R4, and R5 are independently absent or selected from the group consisting of H, halide, unsubstituted —(C1-3 haloalkyl), and unsubstituted —(C1-3 alkyl);
• R3 is selected from the group consisting of -aryl optionally substituted with 1-5 R7 and -heteroaryl optionally substituted with 1-4 R8;
• R6 is selected from the group consisting of —(C1-4 alkylene)paryl substituted with 1-5 R9, —(C2-4 alkenylene)paryl substituted with 1-5 R9, —(C1-4 alkylene)pheteroaryl optionally substituted with 1-6 R10;
• —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R11, —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R12, —(C1-4 alkylene)N(R13)(R14), —N(R15)(R16), —CF(C1-9 alkyl)2, —(C1-4 alkylene)pO(C3-9 alkyl), and —(C2-9 alkynyl) optionally substituted with one or more halides;
• wherein each alkyl of —CF(C1-9 alkyl)2 is, independently, optionally substituted with one or more halides;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• wherein —(C1-4 alkenylene) is, optionally substituted with one or more substituents;
• R7 is selected from the group consisting of halide and —N(R17)2;
• each R8 is independently selected from the group consisting of H, halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —CN, —N(R15)(R18), —(C1-4 alkylene)pXR19, —C(═O)N(R5)2, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R20, and -carbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• alternatively, two adjacent R8 are taken together to form a ring which is selected from the group consisting of -heterocyclyl optionally substituted with 1-10 R22 and -carbocyclyl optionally substituted with 1-12 R21;
• each R9 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —XR23, C(═O)N(R5)2, —(C1-4 alkylene)pN(R24)2, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R22, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• with the proviso that when Y2 is N then R9 is not —OMe or
• each R10 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —CN, —XR23, —C(═O)N(R15)2, —(C1-4 alkylene)pN(R24)2, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R22, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R11 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-4 alkylene)pOR19, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R22, —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21, —N(R15)(R25), —C(═O)(R26), —(C1-4 alkylene)C(═O)OR27, —(C1-4 alkylene)aryl optionally substituted with one or more halides, —(C1-4 alkylene)pheteroaryl optionally substituted with one or more halides, and —SO2(R28);
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• alternatively, two R11 attached to the same carbon atom can together represent ═O to form a carbonyl group;
• each R12 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-4 alkylene)pOR19, —N(R15)(R29), —C(═O)(R26), —C(═O)OR27, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R22, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• R13 is selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R20, and -carbocyclyl optionally substituted with 1-12 R21;
• wherein —(C1-4 alkylene) is, optionally substituted with one or more substituents;
• R14 is selected from the group consisting of unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R20, and -carbocyclyl optionally substituted with 1-12 R21;
• wherein —(C1-4 alkylene) is, optionally substituted with one or more substituents;
• each R15 is selected from the group consisting of H, unsubstituted —(C1-s alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), and unsubstituted —(C1-5 haloalkyl);
• R16 is selected from the group consisting of —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R20, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• R17 is independently selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), and unsubstituted —(C1-5 haloalkyl);
• alternatively, two adjacent R17 are taken together to form a -heterocyclyl ring optionally substituted with 1-10 R22;
• R18 is independently selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C═O)R5, and —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl);
• wherein —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R19 is independently selected from the group consisting of H, unsubstituted —(C1-s alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R20 independently is selected from the group consisting of halide, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —CN, —OH, —N(R5)2, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R21 is independently selected from the group consisting of halide, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), and —CN;
• each R22 is independently selected from the group consisting of halide, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —CN, —OH, —N(R15)2, —C(═O)R34, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R23 is independently selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)N(R15)2, —(C1-4 alkylene)paryl optionally substituted with 1-10 R30, —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-12 R31, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R24 is independently selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), and —(C1-4 alkylene)N(R15)2;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R25 is selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R32, —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21, —(C1-4 alkylene)OR33;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• R26 is selected from the group consisting of H, unsubstituted —(C3-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)paryl optionally substituted with one or more halides or unsubstituted —(C1-5 alkyl), —(C1-4 alkylene)pheteroaryl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), and —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl);
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• R27 is selected from the group consisting of H, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)paryl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), —(C1-4 alkylene)pheteroaryl optionally substituted with one or more halides or unsubstituted —(C1-5 alkyl), and —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl);
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• R28 is selected from the group consisting of unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)paryl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), —(C1-4 alkylene)pheteroaryl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl), and —(C1-4 alkylene)pheterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl);
• wherein —(C1-4 alkylene) is, optionally substituted with one or more substituents;
• each R29 is selected from the group consisting of H, unsubstituted —(C1-s alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —(C1-4 alkylene)pheterocyclyl optionally substituted with 1-10 R32, —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21, —(C1-4 alkylene)OR33, and —C(═O)O(C1-5 alkyl);
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R30 is independently selected from the group consisting of halide, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), and —CN;
• each R31 is independently selected from the group consisting of halide, unsubstituted —(C1-5 alkyl), unsubstituted —(C2-5 alkenyl), unsubstituted —(C2-5 alkynyl), unsubstituted —(C1-5 haloalkyl), —CN, —OH, —C(═O)R34, —N(R24)2, and —(C1-4 alkylene)pcarbocyclyl optionally substituted with 1-12 R21;
• wherein each —(C1-4 alkylene) is, independently, optionally substituted with one or more substituents;
• each R32 is independently selected from the group consisting of halide and unsubstituted —(C1-5 alkyl);
• each R33 is independently selected from the group consisting of H and unsubstituted —(C1-5 alkyl);
• each R34 is independently selected from the group consisting of —O(C15 alkyl) and a heteroaryl optionally substituted with 1-6 R35;
• each R35 is a -heterocyclyl optionally substituted with one or more halides or one or more unsubstituted —(C1-5 alkyl);
• each X is selected from the group consisting of O and S;
• Y3 is CH or nitrogen;
• Y1, Y2, Y4, and Y5 are independently selected from the group consisting of carbon and nitrogen;
• wherein
• if Y1 is nitrogen then Y2, Y4, and Y5 are carbon, Y3 is CH, and R4 is absent;
• if Y2 is nitrogen then Y1, Y4, and Y5 are carbon, Y3 is CH, and R5 is absent;
• if Y3 is nitrogen then Y1, Y2, Y4, and Y5 are carbon;
• if Y4 is nitrogen then Y1, Y2, and Y5 are carbon, Y3 is CH, and R1 is absent;
• if Y5 is nitrogen then Y1, Y2, and Y4 are carbon, Y3 is CH, and R2 is absent;
• each p is independently 0 or 1;
• and
• wherein the compound of Formula I is selected from the group consisting of
• or a pharmaceutically acceptable salt thereof.