Small molecules that enable cartilage rejuvanationThere are provided, inter alia, methods and compounds for activating a proliferative program in competent adult chondrocytes.The compound of structure formula (iii) or its pharmaceutically acceptable salt：wherein：a is cr14or n；b is cr16or n；x is o, nr19or s；l1it is key or substituted or unsubstituted c1-c3alkylidene；n1 is 0-4 integer；m1 and v1 is independently 1 or 2；r8it is hydrogen, halogen ,-cx8.13、-chx8.12、-ch2x8.1、-cn、-son1r8a、-sov1nr8br8c、-nhnr8br8c、- onr8br8c、-nhc(o)nhnr8br8c、-nhc(o)nr8br8c、-n(o)m1、-nr8br8c、-c(o)r8d、-c(o)or8d、-c(o) nr8br8c、-or8a、-nr8bso2r8a、-nr8bc(o)r8d、-nr8bc(o)or8d、-nr8bor8d、-ocx8.13、-ochx8.12, taken generation or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or unsubstituted cycloalkyl, quilt substitution or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted miscellaneous aryl；r9it is hydrogen, halogen ,-cx9.13、-chx9.12、-ch2x9.1、-cn、-son1r9a、-sov1nr9br9c、-nhnr9br9c、- onr9br9c、-nhc(o)nhnr9br9c、-nhc(o)nr9br9c、-n(o)m1、-nr9br9c、-c(o)r9d、-c(o)or9d、-c(o) nr9br9c、-or9a、-nr9bso2r9a、-nr9bc(o)r9d、-nr9bc(o)or9d、-nr9bor9d、-ocx9.13、-ochx9.12, taken generation or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or unsubstituted cycloalkyl, quilt substitution or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted miscellaneous aryl；r10it is hydrogen, halogen ,-cx10.13、-chx10.12、-ch2x10.1、-cn、-son1r10a、-sov1nr10br10c、-nhnr10br10c、- onr10br10c、-nhc(o)nhnr10br10c、-nhc(o)nr10br10c、-n(o)m1、-nr10br10c、-c(o)r10d、-c(o)or10d、- c(o)nr10br10c、-or10a、-nr10bso2r10a、-nr10bc(o)r10d、-nr10bc(o)or10d、-nr10bor10d、-ocx10.13、- ochx10.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r11it is hydrogen, halogen ,-cx11.13、-chx11.12、-ch2x11.1、-cn、-son1r11a、-sov1nr11br11c、-nhnr11br11c、- onr11br11c、-nhc(o)nhnr11br11c、-nhc(o)nr11br11c、-n(o)m1、-nr11br11c、-c(o)r11d、-c(o)or11d、- c(o)nr11br11c、-or11a、-nr11bso2r11a、-nr11bc(o)r11d、-nr11bc(o)or11d、-nr11bor11d、-ocx11.13、- ochx11.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r12it is hydrogen, halogen ,-cx12.13、-chx12.12、-ch2x12.1、-cn、-son1r12a、-sov1nr12br12c、-nhnr12br12c、- onr12br12c、-nhc(o)nhnr12br12c、-nhc(o)nr12br12c、-n(o)m1、-nr12br12c、-c(o)r12d、-c(o)or12d、- c(o)nr12br12c、-or12a、-nr12bso2r12a、-nr12bc(o)r12d、-nr12bc(o)or12d、-nr12bor12d、-ocx12.13、- ochx12.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r13it is hydrogen, halogen ,-cx13.13、-chx13.12、-ch2x13.1、-cn、-son1r13a、-sov1nr13br13c、-nhnr13br13c、- onr13br13c、-nhc(o)nhnr13br13c、-nhc(o)nr13br13c、-n(o)m1、-nr13br13c、-c(o)r13d、-c(o)or13d、- c(o)nr13br13c、-or13a、-nr13bso2r13a、-nr13bc(o)r13d、-nr13bc(o)or13d、-nr13bor13d、-ocx13.13、- ochx13.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r14it is hydrogen, halogen ,-cx14.13、-chx14.12、-ch2x14.1、-cn、-son1r14a、-sov1nr14br14c、-nhnr14br14c、- onr14br14c、-nhc(o)nhnr14br14c、-nhc(o)nr14br14c、-n(o)m1、-nr14br14c、-c(o)r14d、-c(o)or14d、- c(o)nr14br14c、-or14a、-nr14bso2r14a、-nr14bc(o)r14d、-nr14bc(o)or14d、-nr14bor14d、-ocx14.13、- ochx14.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r15it is hydrogen, halogen ,-cx15.13、-chx15.12、-ch2x15.1、-cn、-son1r15a、-sov1nr15br15c、-nhnr15br15c、- onr15br15c、-nhc(o)nhnr15br15c、-nhc(o)nr15br15c、-n(o)m1、-nr15br15c、-c(o)r15d、-c(o)or15d、- c(o)nr15br15c、-or15a、-nr15bso2r15a、-nr15bc(o)r15d、-nr15bc(o)or15d、-nr15bor15d、-ocx15.13、- ochx15.12, it is substituted or unsubstituted alkyl, substituted or unsubstituted miscellaneous alkyl, substituted or do not taken the cycloalkyl in generation, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl；r16it is hydrogen, halogen ,-cx16.13、-chx16.12、-ch2x16.1、-cn、-son1r16a、-sov1nr16br16c、-nhnr16br16c、- onr16br16c、-nhc(o)nhnr16br16c、-nhc(o)nr16br16c、-n(o)m1、-nr16br16c、-c(o)r16d、-c(o)or16d、- c(o)nr16br16c、-or16a、-nr16bso2r16a、-nr16bc(o)r16d、-nr16bc(o)or16d、-nr16bor16d、-ocx16.13、- ochx16.12, it is...
연골 재생을 가능하게 하는 소분자본 발명은 특히 적격한 성체 연골세포에서 증식성 프로그램을 활성화시키기 위한 방법 및 화합물을 제공한다. 화학식 (III)의 화합물 또는 이의 약학적으로 허용되는 염:[이미지](상기 식에서, A는 CR14 또는 N이고;B는 CR16 또는 N이고;X는 O, NR19 또는 S이고;L1은 결합 또는 치환 또는 비치환된 C1-C3 알킬렌이고;n1은 0 내지 4의 정수이고;m1 및 v1은 독립적으로 1 또는 2이고; R8은 수소, 할로겐, -CX8.13, -CHX8.12, -CH2X8.1, -CN, -SOn1R8A, -SOv1NR8BR8C, -NHNR8BR8C, -ONR8BR8C, -NHC(O)NHNR8BR8C, -NHC(O)NR8BR8C, -N(O)m1, -NR8BR8C, -C(O)R8D, -C(O)OR8D, -C(O)NR8BR8C, -OR8A, -NR8BSO2R8A, -NR8BC(O)R8D, -NR8BC(O)OR8D, -NR8BOR8D, -OCX8.13, -OCHX8.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R9는 수소, 할로겐, -CX9.13, -CHX9.12, -CH2X9.1, -CN, -SOn1R9A, -SOv1NR9BR9C, -NHNR9BR9C, -ONR9BR9C, -NHC(O)NHNR9BR9C, -NHC(O)NR9BR9C, -N(O)m1, -NR9BR9C, -C(O)R9D, -C(O)OR9D, -C(O)NR9BR9C, -OR9A, -NR9BSO2R9A, -NR9BC(O)R9D, -NR9BC(O)OR9D, -NR9BOR9D, -OCX9.13, -OCHX9.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R10은 수소, 할로겐, -CX10.13, -CHX10.12, -CH2X10.1, -CN, -SOn1R10A, -SOv1NR10BR10C, -NHNR10BR10C, -ONR10BR10C, -NHC(O)NHNR10BR10C, -NHC(O)NR10BR10C, -N(O)m1, -NR10BR10C, -C(O)R10D, -C(O)OR10D, -C(O)NR10BR10C, -OR10A, -NR10BSO2R10A, -NR10BC(O)R10D, -NR10BC(O)OR10D, -NR10BOR10D, -OCX10.13, -OCHX10.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R11은 수소, 할로겐, -CX11.13, -CHX11.12, -CH2X11.1, -CN, -SOn1R11A, -SOv1NR11BR11C, -NHNR11BR11C, -ONR11BR11C, -NHC(O)NHNR11BR11C, -NHC(O)NR11BR11C, -N(O)m1, -NR11BR11C, -C(O)R11D, -C(O)OR11D, -C(O)NR11BR11C, -OR11A, -NR11BSO2R11A, -NR11BC(O)R11D, -NR11BC(O)OR11D, -NR11BOR11D, -OCX11.13, -OCHX11.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R12는 수소, 할로겐, -CX12.13, -CHX12.12, -CH2X12.1, -CN, -SOn1R12A, -SOv1NR12BR12C, -NHNR12BR12C, -ONR12BR12C, -NHC(O)NHNR12BR12C, -NHC(O)NR12BR12C, -N(O)m1, -NR12BR12C, -C(O)R12D, -C(O)OR12D, -C(O)NR12BR12C, -OR12A, -NR12BSO2R12A, -NR12BC(O)R12D, -NR12BC(O)OR12D, -NR12BOR12D, -OCX12.13, -OCHX12.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R13은 수소, 할로겐, -CX13.13, -CHX13.12, -CH2X13.1, -CN, -SOn1R13A, -SOv1NR13BR13C, -NHNR13BR13C, -ONR13BR13C, -NHC(O)NHNR13BR13C, -NHC(O)NR13BR13C, -N(O)m1, -NR13BR13C, -C(O)R13D, -C(O)OR13D, -C(O)NR13BR13C, -OR13A, -NR13BSO2R13A, -NR13BC(O)R13D, -NR13BC(O)OR13D, -NR13BOR13D, -OCX13.13, -OCHX13.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R14는 수소, 할로겐, -CX14.13, -CHX14.12, -CH2X14.1, -CN, -SOn1R14A, -SOv1NR14BR14C, -NHNR14BR14C, -ONR14BR14C, -NHC(O)NHNR14BR14C, -NHC(O)NR14BR14C, -N(O)m1, -NR14BR14C, -C(O)R14D, -C(O)OR14D, -C(O)NR14BR14C, -OR14A, -NR14BSO2R14A, -NR14BC(O)R14D, -NR14BC(O)OR14D, -NR14BOR14D, -OCX14.13, -OCHX14.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R15는 수소, 할로겐, -CX15.13, -CHX15.12, -CH2X15.1, -CN, -SOn1R15A, -SOv1NR15BR15C, -NHNR15BR15C, -ONR15BR15C, -NHC(O)NHNR15BR15C, -NHC(O)NR15BR15C, -N(O)m1, -NR15BR15C, -C(O)R15D, -C(O)OR15D, -C(O)NR15BR15C, -OR15A, -NR15BSO2R15A, -NR15BC(O)R15D, -NR15BC(O)OR15D, -NR15BOR15D, -OCX15.13, -OCHX15.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R16은 수소, 할로겐, -CX16.13, -CHX16.12, -CH2X16.1, -CN, -SOn1R16A, -SOv1NR16BR16C, -NHNR16BR16C, -ONR16BR16C, -NHC(O)NHNR16BR16C, -NHC(O)NR16BR16C, -N(O)m1, -NR16BR16C, -C(O)R16D, -C(O)OR16D, -C(O)NR16BR16C, -OR16A, -NR16BSO2R16A, -NR16BC(O)R16D, -NR16BC(O)OR16D, -NR16BOR16D, -OCX16.13, -OCHX16.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R17은 수소, 할로겐, -CX17.13, -CHX17.12, -CH2X17.1, -CN, -SOn1R17A, -SOv1NR17BR17C, -NHNR17BR17C, -ONR17BR17C, -NHC(O)NHNR17BR17C, -NHC(O)NR17BR17C, -N(O)m1, -NR17BR17C, -C(O)R17D, -C(O)OR17D, -C(O)NR17BR17C, -OR17A, -NR17BSO2R17A, -NR17BC(O)R17D, -NR17BC(O)OR17D, -NR17BOR17D, -OCX17.13, -OCHX17.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고; R18은 수소, 할로겐, -CX18.13, -CHX18.12, -CH2X18.1, -CN, -SOn1R18A, -SOv1NR18BR18C, -NHNR18BR18C, -ONR18BR18C, -NHC(O)NHNR18BR18C, -NHC(O)NR18BR18C, -N(O)m1, -NR18BR18C, -C(O)R18D, -C(O)OR18D, -C(O)NR18BR18C, -OR18A, -NR18BSO2R18A, -NR18BC(O)R18D, -NR18BC(O)OR18D, -NR18BOR18D, -OCX18.13, -OCHX18.12, 치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 또는 치환 또는 비치환된 헤테로아릴이고;R19는 수소, -COR19D, -C(O)NHNR19BR19C, -C(O)OR19D, -SO2R19A, C(O)NR19BR19C,치환 또는 비치환된 알킬, 치환 또는 비치환된 헤테로알킬, 치환 또는 비치환된 시클로알킬, 치환 또는 비치환된 헤테로시클로알킬, 치환 또는 비치환된 아릴, 치환 또는 비치환된 헤테로아릴이고;R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8C, R8D, R9A, R9B, R9C, R9D, R10A, R10B, R10C, R10D, R11A, R11B, R11C, R11D, R12A, R12B, R12C, R12D, R13A, R13...