(S)-N-Fmoc-α-甲基-2-氟苯丙氨酸 | 1172127-44-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (S)-N-Fmoc-α-甲基-2-氟苯丙氨酸
• 中文别名: FMOC-伪-ME-L-PHE(2-F)-OH；(S)-N-FMOC-A-甲基-2-氟苯；FMOC-伪-ME-PHE(2-F)-OH；(S)-N-芴甲氧羰基-Α-甲基-2-氟苯丙氨酸；FMOC-3-氟-Α-甲基-L-苯丙氨酸；(S)-2-((((9H-氟-9-基)甲氧基)羰基)氨基)-3-(2-氟苯基)-2-甲基丙酸；(S)-N-FMOC-ALPHA-甲基-2-氟苯丙氨酸
• 英文名称: Fmoc-(S)-alpha-Me-o-fluoroPhe-OH
• 英文别名: Fmoc-2-MePhe(2F)-OH；(S)-N-Fmoc-α-methyl-2-fluorophenylalanine；Fmoc-[α-Me-Phe(2-F)-OH]；N-Fmoc-(S)-2-fluoro-α-methylphenylalanine；(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(2-fluorophenyl)-2-methylpropanoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(2-fluorophenyl)-2-methylpropanoic acid
• CAS: 1172127-44-4
• 化学式: C₂₅H₂₂FNO₄
• 分子量: 419.452
• InChiKey: VNYGHKCAXQKZEQ-VWLOTQADSA-N

物化性质

• 沸点：
  621.5±55.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• TSCA：
  No
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  Boc-4-碘-L-苯丙氨酸 、 (S)-N-Fmoc-α-甲基-2-氟苯丙氨酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity

  摘要：

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.

  DOI：

  10.1021/jm900752a
• 作为产物：
  描述：

  在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.35h， 生成 (S)-N-Fmoc-α-甲基-2-氟苯丙氨酸
  参考文献：
  名称：

  Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity

  摘要：

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.

  DOI：

  10.1021/jm900752a

文献信息

• [EN] METHODS OF MAKING INCRETIN ANALOGS<br/>[FR] PROCÉDÉS DE FABRICATION D'ANALOGUES D'INCRÉTINE
  申请人：LILLY CO ELI

  公开号：WO2021034815A1

  公开（公告）日：2021-02-25

  Intermediate compounds are disclosed for making incretin analogs, or pharmaceutically acceptable salts thereof. In addition, methods are disclosed for making incretin analogs by coupling from two to four of the intermediate compounds herein via hybrid liquid solid phase synthesis or native chemical ligation.

  本发明公开了制备胰高血糖素类似物或其药用可接受盐的中间化合物。此外，本发明还公开了通过混合液固相合成或天然化学连接法，通过将本文中的两到四种中间化合物耦合制备胰高血糖素类似物的方法。
• Method for producing dipeptide derivative containing disubstituted amino acid residue
  申请人：NAGASE & CO., LTD.

  公开号：US09605020B2

  公开（公告）日：2017-03-28

  A method for producing a dipeptide that has a protected N-terminal and is represented by formula (1) or a salt of the dipeptide, said method comprising condensing an α-monosubstituted amino acid that has a protected N-terminal and is represented by formula (2) or glycine or a salt thereof with a disubstituted amino acid that is represented by formula (3) or a salt thereof in the presence of a condensing agent [in each of the formulae, substituents are as defined in the description or the like].

  一种用于制备具有受保护N-末端并由化学式（1）表示的二肽或其盐的方法，所述方法包括在存在缩合剂的情况下，将具有受保护N-末端并由化学式（2）表示的α-单取代氨基酸或甘氨酸或其盐与由化学式（3）表示的二取代氨基酸或其盐缩合。【在每个化学式中，取代基如描述或类似物中定义的那样】。
• [EN] ANTIBODY-DRUG CONJUGATES COMPRISING GLP1 PEPTIDOMIMETICS AND USES THEREOF<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT COMPRENANT DES PEPTIDOMIMÉTIQUES DE GLP1 ET LEURS UTILISATIONS
  申请人：REGENERON PHARMA

  公开号：WO2022056494A1

  公开（公告）日：2022-03-17

  Described herein are protein-drug conjugates and compositions thereof that are useful, for example, for targeting glucagon-like peptide 1 receptor (GLP1R). In certain embodiments, provided are peptidomimetic payloads and linker-payloads and methods of making same. More specifically, GLP1 peptidomimetics, antibody-drug conjugates, and compositions which comprise anti-GLP1R antibodies and GLP1 peptidomimetic payloads and methods of treating GLP1R-associated conditions are provided.

  本文描述了蛋白质-药物结合物及其组合物，例如，用于靶向胰高血糖素样肽1受体（GLP1R）。在某些实施例中，提供了肽类类似物荷载和连接器-荷载以及制备它们的方法。更具体地，提供了GLP1类似物、抗体-药物结合物和组合物，其中包括抗GLP1R抗体和GLP1类似物荷载，并提供了治疗GLP1R相关疾病的方法。
• Exploration of structure–activity relationships at the two C-terminal residues of potent 11mer Glucagon-Like Peptide-1 receptor agonist peptides via parallel synthesis
  作者：Tasir S. Haque、Rogelio L. Martinez、Ving G. Lee、Douglas G. Riexinger、Ming Lei、Ming Feng、Barry Koplowitz、Claudio Mapelli、Christopher B. Cooper、Ge Zhang、Christine Huang、William R. Ewing、John Krupinski

  DOI：10.1016/j.peptides.2010.04.013

  日期：2010.7

  We report the identification of potent agonists of the Glucagon-Like Peptide-1 receptor (GLP-1R) via evaluation of two positional scanning libraries and a two-dimensional focused library, synthesized in part on SynPhase (TM) Lanterns. These compounds are 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of biphenylalanine (Bip) at the two C-terminal positions. Typical activities of the most potent peptides in this class are in the picomolar range in an in vitro functional assay using human GLP-1 receptor. (C) 2010 Elsevier Inc. All rights reserved.
• Short Hydrophobic Peptides with Cyclic Constraints Are Potent Glucagon-like Peptide-1 Receptor (GLP-1R) Agonists
  作者：Huy N. Hoang、Kun Song、Timothy A. Hill、David R. Derksen、David J. Edmonds、W. Mei Kok、Chris Limberakis、Spiros Liras、Paula M. Loria、Vincent Mascitti、Alan M. Mathiowetz、Justin M. Mitchell、David W. Piotrowski、David A. Price、Robert V. Stanton、Jacky Y. Suen、Jane M. Withka、David A. Griffith、David P. Fairlie

  DOI：10.1021/acs.jmedchem.5b00166

  日期：2015.5.14

  Cyclic constraints are incorporated into an 11-residue analogue of the N-terminus of glucagon-like peptide-1 (GLP-1) to investigate effects of structure on agonist activity. Cyclization through linking side chains of residues 2 and 5 or 5 and 9 produced agonistis at nM concentrations in a cAMP assay. 2D NMR arid CD spectra revealed an N-terminal beta-turn and a C-terminal helix that differentially influenced affinity and agonist potency. These structures can inform development of small Molecule agonists of the GLP-1 receptor to treat type 2 diabetes.