4-[10-[[(1R)-1-carboxy-4-[2-[2-[2-[2-[2-[2-[[(1S)-1-carboxy-4-oxobutyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-4-oxobutyl]amino]-10-oxodecoxy]benzoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[10-[[(1R)-1-carboxy-4-[2-[2-[2-[2-[2-[2-[[(1S)-1-carboxy-4-oxobutyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-4-oxobutyl]amino]-10-oxodecoxy]benzoic acid
• 化学式: C₃₉H₆₀N₄O₁₆
• 分子量: 840.9
• InChiKey: GZUXWBHSPYNRAS-AJQTZOPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  59
• 可旋转键数：
  38
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  292
• 氢给体数：
  7
• 氢受体数：
  16

文献信息

• Double-acylated GLP-1 derivatives
  申请人：Novo Nordisk A/S

  公开号：US10005827B2

  公开（公告）日：2018-06-26

  The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 27 of GLP-1(7-37) (SEQ ID NO: 1); a second K residue at a position corresponding to position T of GLP-1(7-37), where T is an integer in the range of 7-37 except 18 and 27; and a maximum of ten amino acid changes as compared to GLP-1(7-37); wherein the first K residue is designated K27, and the second K residue is designated KT; which derivative comprises two albumin binding moieties attached to K27 and KT, respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC—(CH2)x—CO— and HOOC—C6H4—O—(CH2)y—CO—; in which x is an integer in the range of 6-16, and y is an integer in the range of 3-17; wherein the linker comprises an element of the formula —NH—(CH2)2—(O—(CH2)2)k—O—(CH2)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 GLP-1 analogs. The derivatives are suitable for oral administration.

  本发明涉及一种 GLP-1 类似物的衍生物，该类似物包括在与 GLP-1(7-37)（SEQ ID NO：1）的位置上的第一个 K 残基；在与 GLP-1(7-37) 的位置 T 相对应的位置上的第二个 K 残基，其中 T 是除 18 和 27 以外的 7-37 范围内的整数；与 GLP-1(7-37) 相比最多有 10 个氨基酸变化；其中第一个 K 残基被命名为 K27，第二个 K 残基被命名为 KT；该衍生物包括两个白蛋白结合基团，分别通过连接体连接到 K27 和 KT，其中白蛋白结合基团包括选自 HOOC-(CH2)x-CO- 和 HOOC-C6H4-O-( )y-CO- 的延长基团；其中x为6-16范围内的整数，y为3-17范围内的整数；其中连接基包括式-NH-( )2-(O-( )2)k-O-( )n-CO-的元素，其中k为1-5范围内的整数，n为1-5范围内的整数；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/或预防各种形式的糖尿病及相关疾病，以及相应的新型 GLP-1 类似物。这些衍生物适用于口服给药。
• DOUBLE-ACYLATED GLP-1 DERIVATIVES
  申请人：Novo Nordisk A/S

  公开号：US20140088005A1

  公开（公告）日：2014-03-27

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 27 of GLP-1(7-37) (SEQ ID NO: 1); a second K residue at a position corresponding to position T of GLP-1(7-37), where T is an integer in the range of 7-37 except 18 and 27; and a maximum of ten amino acid changes as compared to GLP-1(7-37); wherein the first K residue is designated K 27 , and the second K residue is designated K T ; which derivative comprises two albumin binding moieties attached to K 27 and K T , respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC—(CH 2 ) x —CO— and HOOC—C 6 H 4 -0-(CH 2 ) y —CO—; in which x is an integer in the range of 6-16, and y is an integer in the range of 3-17; wherein the linker comprises an element of the formula —NH—(CH 2 ) 2 —(O—(CH 2 ) 2 ) k —O—(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 GLP-1 analogues. The derivatives are suitable for oral administration.
• Double-Acylated GLP-1 Derivatives
  申请人：Novo Nordisk A/S

  公开号：US20170058014A1

  公开（公告）日：2017-03-02

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 27 of GLP-1(7-37) (SEQ ID NO: 1); a second K residue at a position corresponding to position T of GLP-1(7-37), where T is an integer in the range of 7-37 except 18 and 27; and a maximum of ten amino acid changes as compared to GLP-1(7-37); wherein the first K residue is designated K 27 , and the second K residue is designated K T ; which derivative comprises two albumin binding moieties attached to K 27 and K T , respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC—(CH 2 ) x —CO— and HOOC—C 6 H 4 —O—(CH 2 ) y —CO—; in which x is an integer in the range of 6-16, and y is an integer in the range of 3-17; wherein the linker comprises an element of the formula —NH—(CH 2 ) 2 —(O—(CH 2 ) 2 ) k —O—(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 GLP-1 analogues. The derivatives are suitable for oral administration.
• US9266940B2
  申请人：——

  公开号：US9266940B2

  公开（公告）日：2016-02-23
• US9527900B2
  申请人：——

  公开号：US9527900B2

  公开（公告）日：2016-12-27