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    • 4. 发明申请
    • DOUBLE-ACYLATED GLP-1 DERIVATIVES
    • 双取代的GLP-1衍生物
    • WO2012062803A1
    • 2012-05-18
    • PCT/EP2011/069738
    • 2011-11-09
    • NOVO NORDISK A/SMADSEN, Alice RavnWIECZOREK, BirgitKOFOED, JacobLAU, JesperSPETZLER, JaneKODRA, János TiborLINDEROTH, LarsGARIBAY, Patrick WilliamSAUERBERG, PerKRUSE, Thomas
    • MADSEN, Alice RavnWIECZOREK, BirgitKOFOED, JacobLAU, JesperSPETZLER, JaneKODRA, János TiborLINDEROTH, LarsGARIBAY, Patrick WilliamSAUERBERG, PerKRUSE, Thomas
    • A61K47/48C07K14/605A61P3/10
    • C07K14/605A61K47/542
    • The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 18 of GLP-1 (7-37) (SEQ ID NO: 1 ), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1 (7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1, Chem. 2, and Chem. 3: Chem. : HOOC-(CH 2 ) x -CO-* Chem. 2: HOOC-C 6 H 4 -0-(CH 2 ) y -CO-* Chem. 3: R 2 -C 6 H 4 -(CH 2 ) z -CO-*, in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1 -5, and R 2 is a group having a molar mass not higher than 150 Da; and the linker comprises Chem. 4: *-NH-(CH 2 ) 2 -(0-(CH 2 ) 2 ) k -0-(CH 2 ) n -CO-*. wherein k is an integer in the range of 1 -5, and n is an integer in the range of 1 -5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
    • 本发明涉及GLP-1类似物的衍生物,其类似物包含在对应于GLP-1(7-37)(SEQ ID NO:1)的第18位的位置处的第一个K残基,另一个的第二个K残基 位置和与GLP-1(7-37)相比最多12个氨基酸变化; 该衍生物分别包含通过接头分别连接到所述第一和第二K残基的两个伸长部分,其中伸长部分选自Chem。 1,Chem。 2和Chem。 3:Chem。 :HOOC-(CH2)x-CO- * Chem。 2:HOOC-C6H4-0-(CH2)y-CO- * Chem。 3:R2-C6H4-(CH2)z-CO- *,其中x是6-18的整数,y是3-17的整数,z是1的整数 -5和R2是摩尔质量不高于150Da的基团; 连接体包括Chem。 4:* -NH-(CH 2)2 - (O-(CH 2)2)k -O-(CH 2)n -CO- *。 其中k是1-5的整数,n是1-5的整数; 或其药学上可接受的盐,酰胺或酯。 本发明还涉及其药物用途,例如用于治疗和/或预防所有形式的糖尿病和相关疾病,以及相应的新型肽和侧链中间体。 该衍生物适用于口服给药。