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    • 3. 发明申请
    • CYSTEINE PROTEASE INHIBITORS
    • CYSTEINE PROTEASE抑制剂
    • WO2007006714A1
    • 2007-01-18
    • PCT/EP2006/063950
    • 2006-07-06
    • MEDIVIR ABKANGASMETSA, JussiHISCOCK, StephenJOHNSON, TonySAMUELSSON, BertilTOZER, MattGRABOWSKA, Urszula
    • KANGASMETSA, JussiHISCOCK, StephenJOHNSON, TonySAMUELSSON, BertilTOZER, MattGRABOWSKA, Urszula
    • C07D487/04A61K31/407A61P19/10
    • C07D487/04
    • Compounds of the formula II wherein R 1 and R 1, are halo; or one of R 1 and R 1, is halo, and the other is is H; R 2 is R 4 , -C(=O)R 4 ; -OC(=O)R 4 , -S(=O) n R 4 , -S(=O)nNRdRe; R 3 is H, -OR 4 , -SR 4 ; R 3' is H; or R 3 and R 3' together define =O; R 4 is -C 1 C 6 alkyl, -C 0 -C 3 alkylenecarbocyclyl or -C 0 -C 3 alkyleneheterocyclyl, any of which is optionally substituted with up to three substituents selected from R 7 ; R 5 is -C 1 C 5 alkyl, -CH 2 CR 5" C 3 -C 4 -cycloalkyl; R 5' is H; or R 5 and R 5' together with the carbon to which they are attached define C 4 -C 6 -cycloalkyl; R 5" is H, C 1 C 2 alkyl, C 1 C 2 haloalkyl, hydroxyl, OC 1 C 2 alkyl, fluoro; E is -C(=O)-, -S(=O) m -, -NRaS(=O) m -, -NRaC(=O)-, -OC(=O)-, -CRbRc-; R 6 is a stable, optionally substituted, monocyclic or bicyclic carbocycle or heterocycle, wherein the, or each, ring has 4, 5 or 6 ring atoms and 0 to 3 hetero atoms selected from S, O and N; have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepisn K, such as osteoporosis, osteoarthritis, rhuematoid arthritis or bone metastases.
    • 其中R 1和R 2的式II化合物是卤素; 或R 1和R 2中的一个为卤素,另一个为H; R 2是R 4,-C(= O)R 4; -OC(= O)R 4,-S(= O)n R 4,-S(= O)n NR d Re; R 3是H,-OR 4,-SR 4; R 3'是H; 或R 3和R 3'一起定义= O; R 4是-C 1 -C 6烷基,-C 0 -C 3 -C 3 亚烷基环丙基或-C 0 -C 3亚烷基杂环基,其中任何一个任选被至多三个选自R 7的取代基取代; R 5是-C 1 -C 5烷基,-CH 2 CH 2,5“ > C 3 -C 4 - 环烷基; R 5'是H;或R 5和R SUP > 5'与它们所连接的碳一起定义为C 4 -C 6 - 环烷基; R 5“是 H,C 1 -C 2烷基,C 1 -C 2卤代烷基,羟基,OC 1, 氟; C 1 -C 6烷基,氟; E是-C(= O) - , - S(= O)m - , - NR a(= O)m - , - NR a C(= O) - , -OC(= O) - , - CR b R c-; R 6是稳定的,任选取代的单环或双环碳环或杂环,其中环或每个环具有4,5或6个环原子和0至3个选自S,O的杂原子和 N; 可用于治疗特征为导管骨K不适当表达或活化的疾病,如骨质疏松症,骨关节炎,类型性关节炎或骨转移。