4-(7-carboxy-heptyloxy)-benzoic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(7-carboxy-heptyloxy)-benzoic acid tert-butyl ester
• 英文别名: 8-[4-[(2-Methylpropan-2-yl)oxycarbonyl]phenoxy]octanoic acid
• 化学式: C₁₉H₂₈O₅
• 分子量: 336.428
• InChiKey: KPPCBCFBGNURMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-溴庚酸乙酯 生成 4-(7-carboxy-heptyloxy)-benzoic acid tert-butyl ester
  参考文献：
  名称：

  Double-acylated GLP-1 derivatives

  摘要：

  本发明涉及一种GLP-1肽的衍生物，该肽包括第一个K残基和第二个K残基，分别对应于GLP-1（7-37）（SEQ ID NO：1）的位置26和34，并且与GLP-1（7-37）相比最多有八个氨基酸变化；该衍生物包括两个延长基团，分别通过连接剂连接到所述第一个和第二个K残基上，其中所述延长基团为Chem. 2：HOOC-C6H4-O-(CH2)y-CO- *，其中y为6-13范围内的整数；连接剂包括Chem. 3a：*-NH-(CH2)q-CH[(CH2)w-NR1R2]-CO- *，其中q为0-5范围内的整数，R1和R2独立地表示*-H或*-CH3，w为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/或预防所有形式的糖尿病和相关疾病，以及相应的新型肽和连接剂中间体。这些衍生物具有高效、稳定、持久和适合口服给药的特点。

  公开号：

  US11274135B2

文献信息

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

  公开号：US10308700B2

  公开（公告）日：2019-06-04

  The invention relates to a derivative of a GLP-1 peptide, which peptide has two Lys residues, namely a first and a second Lys residue, and a maximum of eight amino acid changes as compared to GLP-1(7-37) (SEQ ID NO: 3), which derivative comprises two protracting moieties attached to the epsilon amino group of said first and second Lys residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 15: HOOC—(CH2)x—CO—*, and Chem. 16: HOOC—C6H4—O—(CH2)y—CO—*, in which x is an integer in the range of 10-16, and y is an integer in the range of 8-12; and the linker comprises a first linker element *—NH—CH(CH2OH)—CO—*. A preferred linker is gGlu-Ser-Ser-Gly-Ser-Ser-Gly (SEQ ID NO: 2). The derivative of the invention has a very good potency, and a very good binding to the GLP-1 receptor. The invention also relates to the pharmaceutical use of the derivative, for example in the treatment and/or prevention of all forms of diabetes and related diseases.

  本发明涉及一种 GLP-1 肽的衍生物，该肽具有两个 Lys 残基，即第一和第二 Lys 残基，与 GLP-1(7-37)(SEQ ID NO: 3)相比，最多有八个氨基酸变化，该衍生物包括两个通过连接体分别连接到所述第一和第二 Lys 残基的ε氨基上的原基，其中原基选自 Chem.15：HOOC-(CH2)x-CO-*，和 Chem.16：HOOC-C6H4-O-(CH2)y-CO-*，其中 x 是 10-16 范围内的整数，y 是 8-12 范围内的整数；连接基包括第一连接基元 *-NH-CH(CH2OH)-CO-*。一种优选的连接体是 gGlu-Ser-Ser-Gly-Ser-Ser-Gly（SEQ ID NO：2）。本发明的衍生物具有很好的效力，与 GLP-1 受体的结合力也很好。本发明还涉及该衍生物的药物用途，例如用于治疗和/或预防各种形式的糖尿病及相关疾病。
• DOUBLE-ACYLATED GLP-1 DERIVATIVES WITH A LINKER
  申请人：Novo Nordisk A/S

  公开号：EP2637699B1

  公开（公告）日：2018-05-16
• DOUBLE-ACYLATED GLP-1 DERIVATIVES
  申请人：Novo Nordisk A/S

  公开号：EP2637698A1

  公开（公告）日：2013-09-18
• GLP-1 DERIVATIVES
  申请人：Novo Nordisk A/S

  公开号：EP2753642B1

  公开（公告）日：2017-03-01
• Double-Acylated GLP-1 Derivatives
  申请人：Madsen Alice Ravn

  公开号：US20130288960A1

  公开（公告）日：2013-10-31

  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.