1-azido-3,6,9,12-tetraoxapentadec-14-yne | 1192590-91-2

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1-azido-3,6,9,12-tetraoxapentadec-14-yne
• 英文别名: Azido-PEG4-propargyl；3-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]prop-1-yne
• CAS: 1192590-91-2
• 化学式: C₁₁H₁₉N₃O₄
• 分子量: 257.29
• InChiKey: FDQQZUZMUONMHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  51.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-azido-3,6,9,12-tetraoxapentadec-14-yne 在 水 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine
  参考文献：
  名称：

  BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS

  摘要：

  本发明涉及新的双功能化合物和治疗HIV感染的方法。这些双功能小分子通常被称为ARM-H'，通过抑制gp120-CD4相互作用和招募抗DNP抗体到gp120表达细胞上，从而通过正交途径发挥作用，防止细胞感染和HIV的传播。已经证明ARM-H与gp120和gp-120表达的细胞竞争性地结合CD4，从而通过MT-2细胞测定减少病毒的感染性，结合导致三元复合物的形成，招募抗DNP抗体结合到其中，三元复合物中的抗体促进gp120表达细胞的补体依赖性破坏。本文描述了化合物和方法。

  公开号：

  US20120269766A1
• 作为产物：
  描述：

  丙炔基-四甘醇-甲磺酸酯 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 1-azido-3,6,9,12-tetraoxapentadec-14-yne
  参考文献：
  名称：

  Lacosamide Isothiocyanate-Based Agents: Novel Agents To Target and Identify Lacosamide Receptors

  摘要：

  (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique: A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with all appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent Seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2.

  DOI：

  10.1021/jm9012054

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。
• ANTIBODY-DRUG CONJUGATES
  申请人：CHO Pharma Inc.

  公开号：US20180133340A1

  公开（公告）日：2018-05-17

  An antibody-drug conjugate (ADC) has a structure represented by Formula (I): [D 2 -L 2 -Cn 2  y G 2 -Ab-Sg 1 G 1 -L 1 -D 1 ] x Formula (I) or a pharmaceutically acceptable salt thereof, wherein Ab is an antibody without glycans (i.e., the protein portion of an antibody); G 1 and G 2 are glycan moieties, which may be the same or different; Cn 1 and Cn 2 are conjugation moieties, which may be the same or different; L 1 and L 2 are linker moieties, which may be the same or different; D 1 and D 2 are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y≠0.

  一种抗体药物偶联物（ADC）具有以下式（I）所代表的结构： [D2-L2-Cn2yG2-Ab-Sg1G1-L1-D1]x 式（I） 或其药用可接受的盐，其中 Ab是没有糖基的抗体（即抗体的蛋白质部分）； G1和G2是糖基部分，可以相同也可以不同； Cn1和Cn2是结合基部分，可以相同也可以不同； L1和L2是连接基部分，可以相同也可以不同； D1和D2是药物单元，可以相同也可以不同； x和y分别是从0到8的整数，但要求x+y≠0。
• [EN] COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION<br/>[FR] COMPOSITIONS ET PROCÉDÉS ASSOCIÉS À LA CONJUGAISON MOLÉCULAIRE
  申请人：INTOCELL INC

  公开号：WO2021111185A1

  公开（公告）日：2021-06-10

  The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.

  这项发明涉及可以与含有Michael供体基团的生物分子发生共轭反应的活化Michael受体（AMA）化合物，从而提供稳定的血浆抗体药物偶联物（ADCs）。还公开了ADCs的药物组合物。本文还提供了一些应用（例如治疗应用），其中这些组合物是有用的。
• A Modular Approach to Triazole-Containing Chemical Inducers of Dimerisation for Yeast Three-Hybrid Screening
  作者：Fanny Tran、Anahi Odell、Gary Ward、Nicholas Westwood

  DOI：10.3390/molecules180911639

  日期：——

  The yeast three-hybrid (Y3H) approach shows considerable promise for the unbiased identification of novel small molecule-protein interactions. In recent years, it has been successfully used to link a number of bioactive molecules to novel protein binding partners. However despite its potential importance as a protein target identification method, the Y3H technique has not yet been widely adopted, in part due to the challenges associated with the synthesis of the complex chemical inducers of dimerisation (CIDs). The development of a modular approach using potentially “off the shelf” synthetic components was achieved and allowed the synthesis of a family of four triazole-containing CIDs, MTX-Cmpd2.2-2.5. These CIDs were then compared using the Y3H approach with three of them giving a strong positive interaction with a known target of compound 2, TgCDPK1. These results showed that the modular nature of our synthetic strategy may help to overcome the challenges currently encountered with CID synthesis and should contribute to the Y3H approach reaching its full potential as an unbiased target identification strategy.

  酵母三杂交（Y3H）方法在无偏倚识别新型小分子-蛋白质相互作用方面显示出相当的前景。近年来，该方法已成功地将多种生物活性分子与其新的蛋白结合伙伴关联起来。然而，尽管作为蛋白靶点识别方法具有潜在重要性，Y3H技术尚未被广泛采用，部分原因在于合成复杂的化学诱导二聚体（CIDs）所面临的挑战。通过开发一种使用潜在“现成”合成组件的模块化方法，成功合成了含有四唑的CIDs家族，即MTX-Cmpd2.2-2.5。随后，通过Y3H方法比较了这些CIDs，其中三种与化合物2的已知目标TgCDPK1表现出强烈的阳性相互作用。这些结果表明，我们合成策略的模块化性质可能有助于克服目前CID合成所面临的挑战，并应有助于Y3H方法充分发挥其作为无偏倚靶点识别策略的潜力。
• [EN] ANTIBODY-DRUG CONJUGATES COMPRISING ANTI-B7-H3 ANTIBODIES<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT COMPRENANT DES ANTICORPS ANTI-B7-H3
  申请人：INTOCELL INC

  公开号：WO2021260438A1

  公开（公告）日：2021-12-30

  The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications

  本公开涉及抗体药物结合物（ADCs），其中一个或多个活性剂通过连接剂与抗B7-H3抗体结合。连接剂可能包括一个单位，将活性剂共价连接到抗体上。本公开进一步涉及特异性结合B7-H3的单克隆抗体和抗原结合片段、变体、多聚体版本或双特异性抗体，以及在各种治疗、诊断和预防适应症中制备和使用这些抗B7-H3抗体和抗原结合片段的方法。