2-(2-oxo-2-(4-(3-oxo-3-(2-oxoazetidin-1-yl)propyl)phenylamino)ethoxy)acetate pentafluorophenol ester | 1415920-62-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 2-(2-oxo-2-(4-(3-oxo-3-(2-oxoazetidin-1-yl)propyl)phenylamino)ethoxy)acetate pentafluorophenol ester
• 英文别名: (2,3,4,5,6-Pentafluorophenyl) 2-[2-oxo-2-[4-[3-oxo-3-(2-oxoazetidin-1-yl)propyl]anilino]ethoxy]acetate；(2,3,4,5,6-pentafluorophenyl) 2-[2-oxo-2-[4-[3-oxo-3-(2-oxoazetidin-1-yl)propyl]anilino]ethoxy]acetate
• CAS: 1415920-62-5
• 化学式: C₂₂H₁₇F₅N₂O₆
• 分子量: 500.379
• InChiKey: KASNNYYMQLPVEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-(2-oxo-2-(4-(3-oxo-3-(2-oxoazetidin-1-yl)propyl)phenylamino)ethoxy)acetate pentafluorophenol ester 、 1-氨基-3,6,9-三噁-11-十一醇 以 N,N-二甲基甲酰胺 为溶剂， 以77%的产率得到N-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl]-2-[2-oxo-2-[4-[3-oxo-3-(2-oxoazetidin-1-yl)propyl]anilino]ethoxy]acetamide
  参考文献：
  名称：

  Development of a long acting human growth hormone analog suitable for once a week dosing

  摘要：

  Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.104
• 作为产物：
  描述：

  3-(4-硝基苯基)丙酸 在 palladium 10% on activated carbon 、 氢气 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 3.0~25.0 ℃ 、68.95 kPa 条件下， 反应 21.75h， 生成 2-(2-oxo-2-(4-(3-oxo-3-(2-oxoazetidin-1-yl)propyl)phenylamino)ethoxy)acetate pentafluorophenol ester
  参考文献：
  名称：

  PROCESSES FOR PREPARING PEPTIDE CONJUGATES AND LINKERS

  摘要：

  本发明提供了一种制备5b式化合物的方法，以及其中间体，以及用于制备这些类似化合物的新型化合物类。

  公开号：

  US20150031108A1

文献信息

• [EN] ANTIBODY COMPOUNDS WITH REACTIVE ARGININE AND RELATED ANTIBODY DRUG CONJUGATES<br/>[FR] COMPOSÉS D'ANTICORPS AVEC ARGININE RÉACTIVE ET CONJUGUÉS ANTICORPS-MÉDICAMENT ASSOCIÉS
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2020076849A1

  公开（公告）日：2020-04-16

  The present invention provides antibody compounds that contain a substitution of arginine for the reactive lysine residue (Lys99) in the hydrophobic cleft (38C2_Arg). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo moieties that are site-specifically conjugated to the engineered arginine residue in the 38C2_Arg variant antibody. Further provided in the invention are therapeutic applications of the compounds.

  本发明提供了含有在疏水裂缝（38C2_Arg）中对活性赖氨酸残基（Lys99）进行氨基酸替换的抗体化合物。该发明还提供了含有货基团的抗体药物结合物（ADCs），这些货基团被特异性地共轭到38C2_Arg变体抗体中的工程氨基酸残基上。该发明还提供了这些化合物的治疗应用。
• Site-Selective Antibody Functionalization via Orthogonally Reactive Arginine and Lysine Residues
  作者：Dobeen Hwang、Napon Nilchan、Alex R. Nanna、Xiaohai Li、Michael D. Cameron、William R. Roush、HaJeung Park、Christoph Rader

  DOI：10.1016/j.chembiol.2019.05.010

  日期：2019.9

  Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show that replacing the Lys with an arginine (Arg) residue affords an orthogonal ADC assembly that is site-selective and stable. X-ray crystallography confirmed the location of the reactive Arg residue at the bottom of a deep pocket. As the Lys-to-Arg mutation is confined to a single residue in the heavy chain of the DVD-IgG1, heterodimeric assemblies that combine a buried Lys in one arm, a buried Arg in the other arm, and identical light chains, are readily assembled. Furthermore, the orthogonal conjugation chemistry enables the loading of heterodimeric DVD-IgG1s with two different cargos in a one-pot reaction and thus affords a convenient platform for dual-warhead ADCs and other multifaceted antibody conjugates.
• Chromatography- and Lyophilization-Free Synthesis of a Peptide-Linker Conjugate
  作者：Javier Magano、Brandon Bock、John Brennan、Douglas Farrand、Michael Lovdahl、Mark T. Maloney、Durgesh Nadkarni、Wendy K. Oliver、Mark J. Pozzo、John J. Teixeira、Jian Wang、John Rizzo、David Tumelty

  DOI：10.1021/op4002998

  日期：2014.1.17

  An optimized and scalable process to manufacture peptide-linker conjugate 1 is reported that avoids the chromatographic purification and lyophilization that are typically required for the isolation of this type of compound. An operationally simple protocol has been developed that couples the peptide to the linker in DMF followed by precipitation with MeCN. A scalable synthesis of the linker is also described which features the N-acylation of 2-azetidinone promoted by 1-propanephosphonic acid anhydride (T3P). The number of operations during the second step of the synthesis (nitrobenzene reduction to aniline) has been simplified by telescoping the aniline into the next step (reaction with diglycolic anhydride to form an acid), thus avoiding an additional isolation. Finally, two efficient activation methods for the acid have been developed by means of the corresponding pentafluorophenyl (PFP) and p-nitrophenyl (PNP) esters.
• ANTIBODY COMPOUNDS WITH REACTIVE ARGININE AND RELATED ANTIBODY DRUG CONJUGATES
  申请人：The Scripps Research Institute

  公开号：US20210340277A1

  公开（公告）日：2021-11-04

  The present invention provides antibody compounds that contain a substitution of arginine for the reactive lysine residue (Lys99) in the hydrophobic cleft (38C2_Arg). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo moieties that are site-specifically conjugated to the engineered arginine residue in the 38C2_Arg variant antibody. Further provided in the invention are therapeutic applications of the compounds.
• US9352050B2
  申请人：——

  公开号：US9352050B2

  公开（公告）日：2016-05-31