Benzotriazol-1-yl 4-[3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanoyl]benzoate | 1610666-68-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Benzotriazol-1-yl 4-[3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanoyl]benzoate
• CAS: 1610666-68-6
• 化学式: C₃₁H₂₇N₃O₇S₂
• 分子量: 617.703
• InChiKey: IOSNOQUASGUHMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  159
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Benzotriazol-1-yl 4-[3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanoyl]benzoate 、 L-Glu(OtBu)-amidomethyl-15-crown-5 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以37.4 mg的产率得到tert-butyl (4S)-4-[[4-[3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanoyl]benzoyl]amino]-5-oxo-5-(1,4,7,10,13-pentaoxacyclopentadec-2-ylmethylamino)pentanoate
  参考文献：
  名称：

  [EN] CONJUGATES AND CONJUGATING REAGENTS COMPRISING A LINKER THAT INCLUDES AT LEAST TWO (-CH2-CH2-0-) UNITS IN A RING
  [FR] CONJUGUÉS ET RÉACTIFS DE CONJUGAISON COMPRENANT UN LIEUR QUI COMPREND AU MOINS DEUX MOTIFS (-CH2-CH2-O-) DANS UN CYCLE

  摘要：

  一种由蛋白质或肽共轭到治疗、诊断或标记试剂的共轭物，其特征在于该连接剂包含至少两个 ~(CH2-CH2- 0-)~ 单元构成的环，所述环通过环内的单个锚定原子连接到连接剂的其余部分，或者所述环通过环内的两个或更多锚定原子连接到连接剂的其余部分的单一点。

  公开号：

  WO2017178828A1
• 作为产物：
  描述：

  BENZOICACID,4-鈥媅3-鈥媅(4-鈥媘ETHYLPHENYL)鈥媠ULFONYL]鈥鈥-鈥媅[(4-鈥媘ETHYLPHENYL)鈥媠ULFONYL]鈥媘ETHYL]鈥鈥-鈥媜XOPROPYL]鈥 、 1-羟基苯并三唑 在 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 19.33h， 以88%的产率得到Benzotriazol-1-yl 4-[3-(4-methylphenyl)sulfonyl-2-[(4-methylphenyl)sulfonylmethyl]propanoyl]benzoate
  参考文献：
  名称：

  [EN] NOVEL CYTOTOXIC AGENTS AND CONJUGATES THEREOF
  [FR] NOUVEAUX AGENTS CYTOTOXIQUES ET LEURS CONJUGUÉS

  摘要：

  本文提供了一般式I的新型马丹西酮类化合物。本文还提供了将这些化合物通过连接剂连接到结合蛋白上的共轭物，以及将这些化合物通过连接剂连接到至少一个能与结合蛋白发生反应的功能基团的共轭试剂。本文还提供了包含这些化合物和共轭物的药物组合物，涉及这些化合物和共轭物的治疗方法和用途，例如在癌症治疗中，并提供了新的合成过程。

  公开号：

  WO2018051109A1

文献信息

• [EN] CONJUGATES AND CONJUGATING REAGENTS<br/>[FR] CONJUGUÉS ET RÉACTIFS DE CONJUGAISON
  申请人：POLYTHERICS LTD

  公开号：WO2016063006A1

  公开（公告）日：2016-04-28

  The invention relates to a conjugate of a protein or peptide with a therapeutic, diagnostic or labelling agent, said conjugate containing a protein or peptide bonding portion and a polyethylene glycol portion; in which said protein or peptide bonding portion has the general formula: in which Pr represents said protein or peptide, each Nu represents a nucleophile present in or attached to the protein or peptide, each of A and B independently represents a C1-4alkylene or alkenylene chain, and W represents an electron withdrawing group or a group obtained by reduction of an electron withdrawing group; and in which said polyethylene glycol portion is or includes a pendant polyethylene glycol chain which has a terminal end group of formula -CH2CH2OR in which R represents a hydrogen atom, an alkyl group, or an optionally substituted aryl group. Also claimed are a method for making such a conjugate, and novel reagents useful in that method.

  该发明涉及与治疗、诊断或标记试剂结合的蛋白质或肽的共轭物，该共轭物包含蛋白质或肽结合部分和聚乙二醇部分；其中所述蛋白质或肽结合部分具有一般式：其中Pr代表所述蛋白质或肽，每个Nu代表存在于蛋白质或肽中或附着于其上的亲核试剂，A和B各自独立地代表C1-4烷基或烯基链，W代表电子吸引基团或通过还原电子吸引基团获得的基团；以及所述聚乙二醇部分是或包括具有一端基团为-CH2CH2OR的挂链聚乙二醇链，其中R代表氢原子、烷基或可选择取代的芳基。还声明了一种制备这种共轭物的方法以及在该方法中有用的新试剂。
• Cytotoxic agents and conjugates thereof
  申请人：POLYTHERICS LIMITED

  公开号：US10654873B2

  公开（公告）日：2020-05-19

  Provided herein are novel maytansinoid compounds of general formula I. Also provided herein are conjugates comprising the compounds linked to a binding protein via a linker, and conjugating reagents comprising the compounds attached via a linker to at least one functional group capable of reacting with a binding protein. Also provided herein are pharmaceutical compositions comprising the compounds and conjugates, therapeutic methods and uses involving the compounds and conjugates, for example in cancer therapy, and novel synthetic processes.

  本文提供了通式 I 的新型 maytansinoid 化合物。本文还提供了包含通过连接体与结合蛋白连接的化合物的共轭物，以及包含通过连接体与至少一个能与结合蛋白反应的官能团连接的化合物的共轭试剂。本文还提供了包含化合物和共轭物的药物组合物、涉及化合物和共轭物的治疗方法和用途（例如在癌症治疗中）以及新型合成工艺。
• Bridging Disulfides for Stable and Defined Antibody Drug Conjugates
  作者：George Badescu、Penny Bryant、Matthew Bird、Korinna Henseleit、Julia Swierkosz、Vimal Parekh、Rita Tommasi、Estera Pawlisz、Kosma Jurlewicz、Monika Farys、Nicolas Camper、XiaoBo Sheng、Martin Fisher、Ruslan Grygorash、Andrew Kyle、Amrita Abhilash、Mark Frigerio、Jeff Edwards、Antony Godwin

  DOI：10.1021/bc500148x

  日期：2014.6.18

  To improve both the homogeneity and the stability of ADCs, we have developed site-specific drug-conjugating reagents that covalently rebridge reduced disulfide bonds. The new reagents comprise a drug, a linker, and a bis-reactive conjugating moiety that is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments. A disulfide rebridging reagent comprising monomethyl auristatin E (MMAE) was prepared and conjugated to trastuzumab (TRA). A 78% conversion of antibody to ADC with a drug to antibody ratio (DAR) of 4 was achieved with no unconjugated antibody remaining. The MMAE rebridging reagent was also conjugated to the interchain disulfide of a Fab derived from proteolytic digestion of TRA, to give a homogeneous single drug conjugated product. The resulting conjugates retained antigen-binding, were stable in serum, and demonstrated potent and antigen-selective cell killing in in vitro and in vivo cancer models. Disulfide rebridging conjugation is a general approach to prepare stable ADCs, which does not require the antibody to be recombinantly re-engineered for site-specific conjugation.
• NOVEL CYTOTOXIC AGENTS AND CONJUGATES THEREOF
  申请人：Polytherics Limited

  公开号：EP3512856B1

  公开（公告）日：2021-03-24
• Conjugates And Conjugating Reagents
  申请人：POLYTHERICS LIMITED

  公开号：US20170290925A1

  公开（公告）日：2017-10-12

  The invention relates to a conjugate of a protein or peptide with a therapeutic, diagnostic or labelling agent, said conjugate containing a protein or peptide bonding portion and a polyethylene glycol portion; in which said protein or peptide bonding portion has the general formula: in which Pr represents said protein or peptide, each Nu represents a nucleophile present in or attached to the protein or peptide, each of A and B independently represents a C 1-4 alkylene or alkenylene chain, and W′ represents an electron withdrawing group or a group obtained by reduction of an electron withdrawing group; and in which said polyethylene glycol portion is or includes a pendant polyethylene glycol chain which has a terminal end group of formula —CH 2 CH 2 OR in which R represents a hydrogen atom, an alkyl group, or an optionally substituted aryl group. Also claimed are a method for making such a conjugate, and novel reagents useful in that method.