A method of treating a bone or cartilage disease selected from the group consisting of osteoarthritis, bone spur (osteophytes), craniosynostosis, fibrodysplasia ossificans progressive, fibrous dysplasia, giant cell tumor of bone, hip labral tear, meniscal tears, bone/osteoporotic fractures, articular cartilage (chondral) defects, degenerative disc disease, osteochondritis dissecans, osteochondroma, osteopetrosis, relapsing polychondritis, and Salter-Harris fractures in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof:
- wherein:
- R1 is selected from the group consisting of -heteroaryl(R4)q and -heterocyclyl(R5)h;
- R2 is selected from the group consisting of H and halide;
- R3 is selected from the group consisting of H, -heteroaryl(R6)q, -heterocyclyl(R7)h, and -aryl(R8)k;
- each R4 is one substituent attached to the heteroaryl and is independently selected from the group consisting of halide, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R9)h, —(C1-4 alkylene)pcarbocyclyl(R10)j, —(C1-4 alkylene)paryl(R11)k, —NHC(═O)R12, —NR13R14, —(C1-6 alkylene)NR15R16, and —OR22;
- each R5 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R6 is one substituent attached to the heteroaryl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —OCH3, —CN, and —C(═O)R17;
- each R7 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —CN, and —OCH3;
- each R8 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —CN, —OCH3, —(C1-6 alkylene)pNHSO2R17, —NR13(C1-6 alkylene)NR13R14, —(C1-6 alkylene)pNR13R14, and —OR25;
- each R9 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of amino, —(C1-4 alkyl), halide, —CF3, and —CN;
- each R10 is one substituent attached to the carbocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R11 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R12 is independently selected from the group consisting of —(C1-9 alkyl), -heteroaryl(R18)q, -aryl(R19)k, —CH2aryl(R19)k, -carbocyclyl(R20)j, —CH2carbocyclyl(R20)j, —(C1-4 alkylene)pNR23R24, -heterocyclyl(R21)h, and —CH2heterocyclyl(R21)h;
- each R13 is independently selected from the group consisting of H and —(C1-6 alkyl);
- each R14 is independently selected from the group consisting of H, —(C1-6 alkyl), —CH2aryl(R19)k, and —CH2carbocyclyl(R20));
- each R15 is independently selected from the group consisting of H and —(C1-6 alkyl);
- each R16 is independently selected from the group consisting of H, —(C1-6 alkyl), —CH2aryl(R19)k, and —CH2carbocyclyl(R20));
- each R17 is a —(C1-6 alkyl);
- each R18 is one substituent attached to the heteroaryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R19 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R20 is one substituent attached to the carbocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- each R21 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN;
- R22 is selected from the group consisting of H, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R21)h, —(C1-4 alkylene)pcarbocyclyl(R20)j, —(C1-4 alkylene)paryl(R19)k, and —(C1-6 alkylene)pNR23R24;
- each R23 is independently selected from the group consisting of H and —(C1-6 alkyl);
- each R24 is independently selected from the group consisting of H and —(C1-6 alkyl);
- R25 is selected from the group consisting of H, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R21)h, and —(C1-6 alkylene)pNR23R24;
- each p is independently 0 or 1;
- each q is independently 0 to 4;
- each h is independently 0 to 10;
- each k is independently 0 to 5;
- and
- each j is independently 0 to 12.