16-[[(1S)-4-[[(1S)-4-[[(5S)-5-amino-6-[[(5S)-5-amino-6-oxohexyl]amino]-6-oxohexyl]amino]-1-carboxy-4-oxobutyl]amino]-1-carboxy-4-oxobutyl]amino]-16-oxohexadecanoic 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: 16-[[(1S)-4-[[(1S)-4-[[(5S)-5-amino-6-[[(5S)-5-amino-6-oxohexyl]amino]-6-oxohexyl]amino]-1-carboxy-4-oxobutyl]amino]-1-carboxy-4-oxobutyl]amino]-16-oxohexadecanoic acid
• 化学式: C₃₈H₆₈N₆O₁₁
• 分子量: 785.0
• InChiKey: RLDNNGBCVNOTNV-ORYMTKCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  55
• 可旋转键数：
  37
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  297
• 氢给体数：
  9
• 氢受体数：
  13

文献信息

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

  公开号：US10604554B2

  公开（公告）日：2020-03-31

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight 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: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4—O—(CH2)y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NR1R2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *—H or *—CH3, and w is an integer in the range of 0-5; 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 peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.

  本发明涉及一种 GLP-1 类似物的衍生物，该类似物包括一个第一 K 残基和一个第二 K 残基，分别位于与 GLP-1(7-37)(SEQ ID NO: 1)的 26 位和 37 位相对应的位置，与 GLP-1(7-37) 相比最多有 8 个氨基酸变化；该衍生物包括两个通过连接基分别连接到所述第一 K 残基和第二 K 残基的原基，其中原基选自 Chem.1：HOOC-(CH2)x-CO-*，和 Chem.2：HOOC-C6H4-O-( )y-CO-*，其中 x 是 8-16 范围内的整数，y 是 6-13 范围内的整数；连接基包括 Chem.3：*-NH-( )q-CH[( )w-NR1R2]-CO-*，其 CO-* 端与 GLP-1 类似物的第一个或第二个 K 残基的ε氨基相连，其中 q 是 0-5 范围内的整数，R1 和 R2 独立地代表 *-H 或 *-CH3，且 w 是 0-5 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，以及相应的新型肽和连接体中间体。这些衍生物具有强效、稳定、持久和适合口服的特点。
• DOUBLE-ACYLATED GLP-1 DERIVATIVES
  申请人：Novo Nordisk A/S

  公开号：EP2846823A1

  公开（公告）日：2015-03-18
• Double-Acylated GLP-1 Derivatives
  申请人：Novo Nordisk A/S

  公开号：US20150133374A1

  公开（公告）日：2015-05-14

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight 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: HOOC—(CH 2 ) x —CO—*, and Chem. 2: HOOC—C 6 H 4 —O—(CH 2 ) y —CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH 2 ) q —CH[(CH 2 ) w —NR 1 R 2 ]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R 1 and R 2 independently represent *—H or *—CH 3 , and w is an integer in the range of 0-5; 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 peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.
• [EN] DOUBLE-ACYLATED GLP-1 DERIVATIVES<br/>[FR] DÉRIVÉS DU GLP-1 À DOUBLE ACYLATION
  申请人：NOVO NORDISK AS

  公开号：WO2013167454A1

  公开（公告）日：2013-11-14

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight 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: HOOC-(CH2)x-CO-*, and Chem. 2: HOOC-C6H4-O-(CH2)y-CO-*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *-NH-(CH2)q-CH[(CH2)w-NR1R2]-CO-*, which is connected at its CO-* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *-H or *-CH3, and w is an integer in the range of 0-5; 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 peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.