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1. 发明授权

US06316410B1 Parathyroid hormone analogues for the treatment of osteoporosis 有权
标题翻译：甲状旁腺素类似物用于治疗骨质疏松症
公开(公告)号：US06316410B1
公开(公告)日：2001-11-13
申请号：US09406813
申请日：1999-09-22
申请人： Jean-René Barbier , Paul Morley , James F. Whitfield , Gordon E. Willick
发明人： Jean-René Barbier , Paul Morley , James F. Whitfield , Gordon E. Willick
IPC分类号： A61K3800
CPC分类号： C07K14/635 , A61K38/00
摘要： The invention disclosed relates to analogues of human parathyroid hormoneh(PTH) which have increased activities in bone restoration, and increased bioavailablities. The analogues described are either single cyclic (1-28) or (1-29) analogues, or double cyclic (1-28) to (1-31) analogues. The single cyclic analogues are cyclised between amino acid pairs R22 and R26. The double cyclic analogues are cyclised between amino acid pairs 13 and 17, and 22 and 26. Various substitutions of the natural residues for other amino acids are also described. For example, the natural Lys27 residue may be substituted by Leu. Typically, these novel analogues have enhanced abilities to stimulate adenyl cyclase activity in rat osteosarcoma cells, and show increased activities in bone restoration using the ovariectomized rat model.
摘要翻译：所公开的发明涉及人甲状旁腺激素（PTH）的类似物，其具有增加的骨修复活性和增加的生物可利用性。所描述的类似物是单环（1-28）或（1-29）类似物，或双环（1-28）至（1-31）类似物。单个环状类似物在氨基酸对R22和R26之间环化。双环类似物在氨基酸对13和17之间以及22和26之间环化。还描述了其它氨基酸的天然残基的各种取代。例如，天然的Lys27残基可以被Leu取代。通常，这些新型类似物具有增强的刺激大鼠骨肉瘤细胞中腺苷酸环化酶活性的能力，并且使用卵巢切除的大鼠模型显示增加的骨修复活动。

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