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    • 4. 发明申请
    • Novel Glp-1 Derivatives
    • 新型Glp-1衍生物
    • US20070203058A1
    • 2007-08-30
    • US10572348
    • 2004-09-17
    • Jesper LauThomas HansenKjeld MadsenPaw BlochFlorencio DorwaldNils Johansen
    • Jesper LauThomas HansenKjeld MadsenPaw BlochFlorencio DorwaldNils Johansen
    • A61K38/26
    • C07K14/605A61K38/00A61K38/26A61K47/54A61K47/542A61K47/60C07K14/001
    • Novel polypeptide derivatives having protracted profile of action. The present invention relates to a compound which comprises a therapeutic polypeptide linked to an albumin binding residue via a hydrophilic spacer. The present invention also relates to a compound which comprises a therapeutic polypeptide linked to an albumin binding residue via a hydrophilic spacer that separates the polypeptide and the albumin binding residue with a chemical moiety comprising at least 5 non-hydrogen atoms where 30-50% of these atoms are either N or O. In one embodiment of this invention the spacer is defined as —(CH2)lD[(CH2)nE]m(CH2)pQq-, wherein l, m and n independently are 1-20 and p is 0-10, Q is -Z-(CH2)lD[(CH2)nG]m(CH2)p—, q is an integer in the range from 0 to 5, each D, E and G independently are selected from —O—, NR3—, —N(COR4)—, —PR5(O)—, and —P(OR6)(O)—, wherein R3, R4, R5, and R6 independently represent hydrogen or C1-6-alky, Z is selected from —C(O)NH—, —C(O)NHCH2—, —OC(O)NH—, —C(O)NHCH2CH2—, —C(O)CH2—, —C(O)CH═CH—, —(CH2)s—, —C(O)—, —C(O)O— or —NHC(O)—, wherein s is 0 or 1.
    • 新型多肽衍生物具有延长的作用特征。 本发明涉及包含通过亲水间隔物与白蛋白结合残基连接的治疗性多肽的化合物。 本发明还涉及一种化合物,其包含通过亲水间隔物与白蛋白结合残基连接的治疗性多肽,其将多肽和白蛋白结合残基与包含至少5个非氢原子的化学部分分开,其中30-50% 这些原子是N或O.在本发明的一个实施方案中,间隔基被定义为 - (CH 2)2 D [(CH 2)2 (CH 2)n) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 其中l,m和n独立地是1-20,p是0-10,Q是-Z-(CH 2)2 D [(CH 2) (CH 2) - - - - - - - - - - - - - - - - 范围为0至5,每个D,E和G各自独立地选自-O-,NR 3 - , - N(COR 4 - ) - , - PR