Small molecules that enable cartilage rejuvanation

A method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula (III):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• A is CR14 or N;
• B is CR16 or N;
• X is O, NR19 or S;
• L1 is a bond or substituted or unsubstituted C1-C3 alkylene;
• R8 is hydrogen, halogen, —CX8.13, —CHX8.12, —CH2X8.1, —CN, —SOn8R8A, —SOv8NR8BR8C, —NHNR8BR8C, —ONR8BR8C, —NHC(O)NHNR8BR8C, —NHC(O)NR8BR8C, —N(O)m8, —NR8BR8C, —C(O)R8D, —C(O)OR8D, —C(O)NR8BR8C, —OR8A, —NR8BSO2R8A, —NR8BC(O)R8D, —NR8BC(O)OR8D, —NR8BOR8D, —OCX8.13, —OCHX8.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
• R9 is hydrogen, halogen, —CX9.13, —CHX9.12, —CH2X9.1, —CN, —SOn9R9A, —SOv9NR9BR9C, —NHNR9BR9C, —ONR9BR9C, —NHC(O)NHNR9BR9C, —NHC(O)NR9BR9C, —N(O)m9, —NR9BR9C, —C(O)R9D, —C(O)OR9D, —C(O)NR9BR9C, —OR9A, —NR9BSO2R9A, —NR9BC(O)R9D, —NR9BC(O)OR9D, —NR9BOR9D, —OCX9.13, —OCHX9.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R10 is hydrogen, halogen, —CX10.13, —CHX10.12, —CH2X10.1, —CN, —SOn10R10A, —SOv10NR10BR10C, —NHNR10BR10C, —ONR10BR10C, —NHC(O)NHNR10BR10C, —NHC(O)NR10BR10C, —N(O)m10, —NR10BR10C, —C(O)R10D, —C(O)OR10D, —C(O)NR10BR10C, —OR10A, —NR10BSO2R10A, —NR10BC(O)R10D, —NR10BC(O)OR10D, —NR10BOR10D, —OCX10.13, —OCHX10.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R11 is hydrogen, halogen, —CX11.13, —CHX11.12, —CH2X11.1, —CN, —SOn11R11A, —SOv11NR11BR11C, —NHNR11BR11C, —ONR11BR11C, —NHC(O)NHNR11BR11C, —NHC(O)NR11BR11C, —N(O)m11, —NR11BR11C, —C(O)R11D, —C(O)OR11D, —C(O)NR11BR11C, —OR11A, —NR11BSO2R11A, —NR11BC(O)R11D, —NR11BC(O)OR11D, —NR11BOR11D, —OCX11.13, —OCHX11.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R12 is hydrogen, halogen, —CX12.13, —CHX12.12, —CH2X12.1, —CN, —SOn12R12A, —SOv12NR12BR12C, —NHNR12BR12C, —ONR12BR12C, —NHC(O)NHNR12BR12C, —NHC(O)NR12BR12C, —N(O)m12, —NR12BR12C, —C(O)R12D, —C(O)OR12D, —C(O)NR12BR12C, —OR12A, —NR12BSO2R12A, —NR12BC(O)R12D, —NR12BC(O)OR12D, —NR12BOR12D, —OCX12.13, —OCHX12.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R13 is hydrogen, halogen, —CX13.13, —CHX13.12, —CH2X13.1, —CN, —SOn13R13A, —SOv13NR13BR13C, —NHNR13BR13C, —ONR13BR13C, —NHC(O)NHNR13BR13C, —NHC(O)NR13BR13C, —N(O)m13, —NR13BR13C, —C(O)R13D, —C(O)OR13D, —C(O)NR13BR13C, —OR13A, —NR13BSO2R13A, —NR13BC(O)R13D, —NR13BC(O)OR13D, —NR13BOR13D, —OCX13.13, —OCHX13.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R14 is hydrogen, halogen, —CX14.13, —CHX14.12, —CH2X14.1, —CN, —SOn14R14A, —SOv14NR14BR14C, —NHNR14BR14C, —ONR14BR14C, —NHC(O)NHNR14BR14C, —NHC(O)NR14BR14C, —N(O)m14, —NR14BR14C, —C(O)R14D, —C(O)OR14D, —C(O)NR14BR14C, —OR14A, —NR14BSO2R14A, —NR14BC(O)R14D, —NR14BC(O)OR14D, —NR14BOR14D, —OCX14.13, —OCHX14.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R15 is hydrogen, halogen, —CX15.13, —CHX15.12, —CH2X15.1, —CN, —SOn15R15A, —SOv15NR15BR15C, —NHNR15BR15C, —ONR15BR15C, —NHC(O)NHNR15BR15C, —NHC(O)NR15BR15C, —N(O)m15, —NR15BR15C, —C(O)R15D, —C(O)OR15D, —C(O)NR15BR15C, —OR15A, —NR15BSO2R15A, —NR15BC(O)R15D, —NR15BC(O)OR15D, —NR15BOR15D, —OCX15.13, —OCHX15.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R16 is hydrogen, halogen, —CX16.13, —CHX16.12, —CH2X16.1, —CN, —SOn16R16A, —SOv16NR16BR16C, —NHNR16BR16C, —ONR16BR16C, —NHC(O)NHNR16BR16C, —NHC(O)NR16BR16C, —N(O)m16, —NR16BR16C, —C(O)R16D, —C(O)OR16D, —C(O)NR16BR16C, —OR16A, —NR16BSO2R16A, —NR16BC(O)R16D, —NR16BC(O)OR16D, —NR16BOR16D, —OCX16.13, —OCHX16.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R17 is hydrogen, halogen, —CX17.13, —CHX17.12, —CH2X17.1, —CN, —SOn17R17A, —SOv17NR17BR17C, —NHNR17BR17C, —ONR17BR17C, —NHC(O)NHNR17BR17C, —NHC(O)NR17BR17C, —N(O)m17, —NR17BR17C, —C(O)R17D, —C(O)OR17D, —C(O)NR17BR17C, —OR17A, —NR17BSO2R17A, —NR17BC(O)R17D, —NR17BC(O)OR17D, —NR17BOR17D, —OCX17.13, —OCHX17.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R18 is hydrogen, halogen, —CX18.13, —CHX18.12, —CH2X18.1, —CN, —SOn18R18A, —SOv18NR18BR18C, —NHNR18BR18C, —ONR18BR18C, —NHC(O)NHNR18BR18C, —NHC(O)NR18BR18C, —N(O)m18, —NR18BR18C, —C(O)R18D, —C(O)OR18D, —C(O)NR18BR18C, —OR18A, —NR18BSO2R18A, —NR18BC(O)R18D, —NR18BC(O)OR18D, —NR18BOR18D, —OCX18.13, —OCHX18.12, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R19 is hydrogen, —COR19D, —C(O)NHNR19BR19C, —C(O)OR19D—SO2R19A, C(O)NR19BR19C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
• R19A is independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF3, —OCCl3, —OCBr3, —OCI3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, R19AF-substituted or unsubstituted alkyl, R19AF-substituted or unsubstituted heteroalkyl, R19AF-substituted or unsubstituted cycloalkyl, R19AF-substituted or unsubstituted heterocycloalkyl, R19AF-substituted or unsubstituted aryl, or R19AF-substituted or unsubstituted heteroaryl;
• R19B is independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF3, —OCCl3, —OCBr3, —OCI3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, R19BF-substituted or unsubstituted alkyl, R19BF-substituted or unsubstituted heteroalkyl, R19BF-substituted or unsubstituted cycloalkyl, R19BF-substituted or unsubstituted heterocycloalkyl, R19BF-substituted or unsubstituted aryl, or R19BF-substituted or unsubstituted heteroaryl;
• R19C is independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF3, —OCCl3, —OCBr3, —OCI3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, R19CF-substituted or unsubstituted alkyl, R19CF-substituted or unsubstituted heteroalkyl, R19CF-substituted or unsubstituted cycloalkyl, R19CF-substituted or unsubstituted heterocycloalkyl, R19CF-substituted or unsubstituted aryl, or R19CF-substituted or unsubstituted heteroaryl;
• R19D is independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF3, —OCCl3, —OCBr3, —OCI3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, R19DF-substituted or unsubstituted alkyl, R19DF-substituted or unsubstituted heteroalkyl, R19DF-substituted or unsubstituted cycloalkyl, R19DF-substituted or unsubstituted heterocycloalkyl, R19DF-substituted or unsubstituted aryl, or R19DF-substituted or unsubstituted heteroaryl;
• R8A, R8B, R8C, R8D, R9A, R9B, R9C, 9RD, R10A, R10B, R10C, R10D, R11A, R11B, R11C, R11D, R12A, R12B, R12C, R12D, R13A, R13B, R13C, R13D, R14A, R14B, R14C, R14D, R15A, R15B, R15C, R15D, R16A, R16B, R16C, R16D, R17A, R17B, R17C, R17D, R18A, R18B, R18C, R18D, R19AF, R19BF, R19CF, and R19DF are independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF3, —OCCl3, —OCBr3, —OCI3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsbstituted or unsubstituted heteroaryl;
• R8B, R8C, R9B, R9C, R10B, R10C, R11B, R11C, R12B, R13B, R13C, R14B, R14C, R15B, R15C, R16B, R16C, R17B, R17C, R18B, R18C, R19BF and R19CF substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• n8, n9, n10, n11, n12, n13, n14, n15, n16, n17, and n18 is an integer from 0 to 4;
• m8, m9, m10, m11, m12, m13, m14, m15, m16, m17, and m18 are independently 1 or 2;
• v8, v9,v10, v11, v12, v13, v14, v15, v16, v17, and v18 are independently 1 or 2;
• and
• X8.1, X9.1, X10.1, X11.1, X12.1, X13.1, X14.1, X15.1, X16.1, X17.1 and X18.1 are independently —Cl, —Br, —I or —F.