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    • 1. 发明申请
    • CONFORMATIONALLY CONSTRAINED PARATHYROID HORMONE (PTH) ANALOGS WITH LACTAM BRIDGES
    • 连续约束的PARAMYROID HORMONE(PTH)模拟与LACTAM BRIDGES
    • WO2004067021A1
    • 2004-08-12
    • PCT/US2003/002155
    • 2003-01-24
    • GARDELLA, Thomas, J.KRONENBERG, Henry, M.POTTS, John, T.
    • GARDELLA, Thomas, J.KRONENBERG, Henry, M.POTTS, John, T.
    • A61K38/00
    • C07K14/635A61K38/29
    • The present invention relates to methods of treatment of mammalian conditions characterized by decreases in bone mass with conformationally constrained parathyroid hormone (PTH) analogs and derivatives of those analogs containing PTH polypeptide derivatives containing at least one Glu or Lys substitution at position 6 and/or 10, some with installed lactam bridges between the side chains of Lys and Glu. The invention provides derivatives of PTH (1-34), PTH(1-33), PTH(1-32), PTH(1-31), PTH(1-30), PTH(1-29), PTH(1-28), PTH(1-­27), PTH(1-26), PTH(1-25), PTH(1-24), PTH(1-23), PTH(1-22), PTH (1-21), PTH(1-20), PTH(1-19), PTH(1-18), PTH(1-17), PTH(1-16), PTH(1-15), PTH(1-­14), PTH(1-13), PTH(1-12), PTH(1-11), PTH(1-10) and PTH(1-9) polypeptide. The invention also provides methods of preparing the PTH analogs. Further, the invention encompasses treating conditions that are characterized by undesired bone loss or by the need for bone growth, e.g. in treating fractures or cartilage disorders and for raising cAMP levels in cells where deemed necessary.
    • 本发明涉及治疗哺乳动物病症的方法,其特征在于具有构象约束的甲状旁腺激素(PTH)类似物的骨量减少和含有在第6位和/或第10位含有至少一个Glu或Lys取代的PTH多肽衍生物的那些类似物的衍生物 ,一些在Lys和Glu的侧链之间安装了内酰胺桥。 本发明提供了PTH(1-34),PTH(1-33),PTH(1-32),PTH(1-31),PTH(1-30),PTH(1-29),PTH -2TH),PTH(1-27),PTH(1-26),PTH(1-25),PTH(1-24),PTH(1-23),PTH(1-22) 21),PTH(1-20),PTH(1-19),PTH(1-18),PTH(1-17),PTH(1-16),PTH(1-15),PTH ),PTH(1-13),PTH(1-12),PTH(1-11),PTH(1-10)和PTH(1-9)多肽。 本发明还提供了制备PTH类似物的方法。 此外,本发明包括以不良骨丢失或骨生长需要为特征的治疗条件,例如。 在治疗骨折或软骨障碍并提高认为必要的细胞中的cAMP水平。