2,2-dimethyl-N-pyridin-2-ylmethylmalonamic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,2-dimethyl-N-pyridin-2-ylmethylmalonamic acid
• 英文别名: 2,2-dimethyl-3-oxo-3-(pyridin-2-ylmethylamino)propanoic acid
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: VVXMLWBMTPGIIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨甲基吡啶 、 二甲基丙二酸 在 N,N-二异丙基乙胺 、 N-羟基-7-氮杂苯并三氮唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 1.5h， 以41%的产率得到2,2-dimethyl-N-pyridin-2-ylmethylmalonamic acid
  参考文献：
  名称：

  DOUBLE-ACYLATED GLP-1 DERIVATIVES

  摘要：

  公开号：

  EP3000482B1

文献信息

• GLP-1 RECEPTOR AGONIST COMPOUNDS WITH A MODIFIED N-TERMINUS
  申请人：Kodra Janos Tibor

  公开号：US20120329711A1

  公开（公告）日：2012-12-27

  The invention relates to GLP-1 receptor agonist compounds with a modified N-terminus. The compounds are of the formula Chem. 1: Y—Z—P, wherein P represents a fragment of a GLP-1 receptor agonist peptide lacking the two N-terminal amino acid residues; and Y—Z represents novel His-Ala mimetics. Examples of GLP-1 receptor agonist compounds are derived from human GLP-1 (7-37), exendin-4(1-39), or GLP-1 A (1-37). The invention also relates to derivatives of these compounds, in particular compounds with one or more albumin binding side chains capable of protracting the duration of action in vivo of these compounds. The peptides and derivatives of the invention have a good potency, a protracted pharmacokinetic profile, are stable against degradation by gastro intestinal enzymes, and/or have a high oral bioavailability. These properties are of importance in the development of GLP-1 receptor agonist compounds for subcutaneous, intravenous, and/or in particular oral administration. The invention also relates to intermediate products for use in the preparation of the GLP-1 receptor agonist compounds of the invention.

  本发明涉及具有改性N-末端的GLP-1受体激动剂化合物。该化合物的化学式为Chem.1：Y-Z-P，其中P表示GLP-1受体激动肽的一个片段，缺少两个N-末端氨基酸残基；而Y-Z表示新型的His-Ala类似物。GLP-1受体激动剂化合物的例子源自人类GLP-1（7-37）、exendin-4（1-39）或GLP-1A（1-37）。本发明还涉及这些化合物的衍生物，特别是具有一个或多个能够在体内延长作用持续时间的白蛋白结合侧链的化合物。本发明的肽和衍生物具有良好的效力、持久的药代动力学特性、对胃肠道酶的降解稳定性和/或高口服生物利用度。这些特性对于开发用于皮下、静脉内和/或口服给药的GLP-1受体激动剂化合物非常重要。本发明还涉及用于制备本发明的GLP-1受体激动剂化合物的中间产物。
• GLP-1 ANALOGUES AND DERIVATIVES
  申请人：Kalthoff Christoph

  公开号：US20130053311A1

  公开（公告）日：2013-02-28

  The invention relates to a GLP-1 analogue which comprises a histidine (H) residue at a position corresponding to position 31 of GLP-1 (7-37) (SEQ ID NO: 1), a glutamine (Q) residue at a position corresponding to position 34 of GLP-1 (7-37) (SEQ ID NO: 1), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37) (SEQ ID NO: 1); wherein the H residue is designated H 31 , and the Q residue is designated Q 34 ; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to derivatives thereof, as well as the pharmaceutical use of these analogues and derivatives, for example in the treatment and/or prevention of all forms of diabetes and related diseases. The invention furthermore relates to corresponding novel side chain intermediates. The derivatives are suitable for oral administration.

  本发明涉及一种GLP-1类似物，其包括一个组氨酸（H）残基，该残基位于对应于GLP-1（7-37）（SEQ ID NO：1）的31位位置，一个谷氨酰胺（Q）残基，该残基位于对应于GLP-1（7-37）（SEQ ID NO：1）的34位位置，并且与GLP-1（7-37）（SEQ ID NO：1）相比最多具有十个氨基酸修饰；其中，H残基被指定为H31，Q残基被指定为Q34；或其药学上可接受的盐、酰胺或酯。本发明还涉及其衍生物，以及这些类似物和衍生物的药用，例如用于治疗和/或预防所有形式的糖尿病和相关疾病。本发明还涉及相应的新型侧链中间体。这些衍生物适合口服给药。
• GLP-1 analogues and derivatives
  申请人：Kalthoff Christoph

  公开号：US08815802B2

  公开（公告）日：2014-08-26

  The invention relates to a GLP-1 analog which comprises a histidine (H) residue at a position corresponding to position 31 of GLP-1(7-37) (SEQ ID NO: 1), a glutamine (Q) residue at a position corresponding to position 34 of GLP-1 (7-37) (SEQ ID NO: 1), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37) (SEQ ID NO: 1); wherein the H residue is designated H31, and the Q residue is designated Q34; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to derivatives thereof, as well as the pharmaceutical use of these analogs and derivatives, for example in the treatment and/or prevention of all forms of diabetes and related diseases. The invention furthermore relates to corresponding novel side chain intermediates. The derivatives are suitable for oral administration.

  本发明涉及一种GLP-1类似物，其包括一个组氨酸（H）残基，该残基位于与GLP-1（7-37）（SEQ ID NO: 1）的第31个位置相对应的位置，一个谷氨酰胺（Q）残基，该残基位于与GLP-1（7-37）（SEQ ID NO: 1）的第34个位置相对应的位置，并且相对于GLP-1（7-37）（SEQ ID NO: 1）最多有十个氨基酸修饰；其中H残基被指定为H31，Q残基被指定为Q34；或其药学上可接受的盐，酰胺或酯。本发明还涉及其衍生物，以及这些类似物和衍生物的药用，例如用于治疗和/或预防所有形式的糖尿病和相关疾病。本发明还涉及相应的新型侧链中间体。这些衍生物适用于口服给药。
• Double-acylated GLP-1 derivatives
  申请人：Garibay Patrick William

  公开号：US08648041B2

  公开（公告）日：2014-02-11

  The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1(7-37), and a maximum of ten amino acid modifications as compared to GLP-1(7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: Chem. 1, Chem. 2, Chem. 3 or Chem. 4; or a pharmaceutically acceptable salt, amide, or ester thereof.

  该发明涉及一种GLP-1类似物的衍生物，该类似物包括一个位于GLP-1（7-37）（SEQ ID NO:1）的37号位置相应位置的第一个K残基，一个位于GLP-1（7-37）的26号位置相应位置的第二个K残基，以及与GLP-1（7-37）相比最多十个氨基酸修饰，其中第一个K残基被指定为K37，第二个K残基被指定为K26，该衍生物包括两个结合白蛋白的基团，分别连接在K26和K37上，其中结合白蛋白的基团包括从以下化学物质中选择的延长基团：Chem.1、Chem.2、Chem.3或Chem.4；或其药学上可接受的盐、酰胺或酯。
• US8648041B2
  申请人：——

  公开号：US8648041B2

  公开（公告）日：2014-02-11