5-acetyl-5H,6H-11,12-didehydrodibenzo[b,f]azocin

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 5-acetyl-5H,6H-11,12-didehydrodibenzo[b,f]azocin
• 英文别名: 1-(11,12-Didehydrodibenz[b,f]azocin-5(6H)-yl)ethanone；1-(2-azatricyclo[10.4.0.04,9]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-yl)ethanone
• 化学式: C₁₇H₁₃NO
• 分子量: 247.296
• InChiKey: LSIBMABOLKPSEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  4-(1,1-二甲基乙基)-3,5-环己二烯-1,2-二酮 、 5-acetyl-5H,6H-11,12-didehydrodibenzo[b,f]azocin 以 1,2-二氯乙烷 为溶剂， 反应 10.0h， 生成
  参考文献：
  名称：

  Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition: Experimental and Theoretical Studies

  摘要：

  Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cydoalkyne-1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (OH double dagger) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for OH double dagger of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3-8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.

  DOI：

  10.1021/acs.joc.7b02614
• 作为产物：
  描述：

  5-二苯并环庚烯酮 在 吡啶 、 lithium aluminium tetrahydride 、 盐酸羟胺 、 potassium tert-butylate 、 溴 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 5-acetyl-5H,6H-11,12-didehydrodibenzo[b,f]azocin
  参考文献：
  名称：

  光活化荧光叠氮化物-炔烃点击反应：双活化荧光探针

  摘要：

  这种新报道的光活化荧光叠氮化物-炔烃环加成 (PFAAC) 使叠氮化物-炔烃点击反应以时空方式可视化。双激活过程可实现高信噪比。我们可以通过光激活在合适的时间“看到”点击反应。

  DOI：

  10.1002/asia.202200634

文献信息

• TUBULYSIN ANALOGS AND METHODS OF MAKING AND USE
  申请人：Bristol-Myers Squibb Company

  公开号：US20160130299A1

  公开（公告）日：2016-05-12

  Tubulysin analogs of the formula (I) where R 1 , R 2 R 3 , R 4 , R 5 , R 6 , R 7 , and Y are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

  管素类似物公式(I)，其中R1、R2、R3、R4、R5、R6、R7和Y如本文所述定义，是一种抗有丝分裂剂，可用于癌症治疗，特别是在与靶向部分结合时。
• [EN] BIOCONJUGATES CONTAINING SULFAMIDE LINKERS FOR USE IN TREATMENT<br/>[FR] BIOCONJUGUÉS CONTENANT DES SÉQUENCES DE LIAISON SULFAMIDE POUR UTILISATION À DES FINS THÉRAPEUTIQUES
  申请人：SYNAFFIX BV

  公开号：WO2017137456A1

  公开（公告）日：2017-08-17

  The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1).

  本发明基于一个令人惊讶的发现，即生物结合物中使用的连接剂，如抗体药物结合物，不是治疗惰性的，而是对生物结合物的治疗指数产生影响。因此，本发明涉及一种增加生物结合物的治疗指数的方法，以及用于治疗，特别是癌症的生物结合物。根据本发明的生物结合物具有包含符合式（1）的基团的磺酰胺连接剂。
• [EN] NOVEL CRYPTOPHYCIN COMPOUNDS AND CONJUGATES, THEIR PREPARATION AND THEIR THERAPEUTIC USE<br/>[FR] NOUVEAUX COMPOSÉS ET CONJUGUÉS DE CRYPTOPHYCINE, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI SA

  公开号：WO2017076998A1

  公开（公告）日：2017-05-11

  The present invention relates to cryptophycin compounds of formula (I). The invention also relates to cryptophycin payloads, to cryptophycin conjugates, to compositions containing them and to their therapeutic use, especially as anticancer agents. The invention also relates to the process for preparing these conjugates.

  本发明涉及公式（I）的隐藻素化合物。该发明还涉及隐藻素有效载荷、隐藻素偶联物、含有它们的组合物及其治疗用途，尤其是作为抗癌剂。该发明还涉及制备这些偶联物的过程。
• Strain‐Promoted Azide–Alkyne Cycloaddition with Ruthenium(II)–Azido Complexes
  作者：Thomas Cruchter、Klaus Harms、Eric Meggers

  DOI：10.1002/chem.201302502

  日期：2013.12.2

  the determined second‐order rate constant for the ADIBO cycloaddition with the azido complex (k2=6.9 × 10−2 M−1 s−1) is comparable to the rate determined for the ADIBO cycloaddition with organic benzyl azide (k2=4.0 × 10−1 M−1 s−1). Our results demonstrate that it is possible to transfer the concept of strain‐promoted azide–alkyne cycloaddition (SPAAC) from purely organic azides to metal‐coordinated

  研究了示例性的钌（II）-叠氮基络合物在室温和低叠氮化物和炔烃浓度下对未活化的，电子不足的以及对应变活化的炔烃的反应性。在这种条件下，即使在铜（I）催化条件下，未活化的末端炔烃和内部炔烃也无法反应。相反，正如预期的那样，使用缺电子的乙炔二羧酸二甲酯（DMAD）作为双极性亲和剂，观察到了快速的环加成反应。由于DMAD和相关的炔丙基酯是出色的Michael受体，因此不适合生物学应用，因此我们研究了叠氮基络合物与环辛炔（OCT），双环[6.1.0] non-4-yne（BCN）衍生物的环加成反应性，和氮杂二苯并环辛炔（ADIBO）。虽然在应变较小的环辛炔OCT的情况下未观察到反应，但应变较大的环辛炔BCN和ADIBO容易与叠氮基络合物反应，提供了相应的稳定的三唑并合物，可通过常规硅胶柱色谱纯化。获得了ADIBO环加合物的X射线晶体结构，并验证了形成的1,2,3-三唑并配体通过中心N2原子配位金属
• [EN] BIOMOLECULE CONJUGATES<br/>[FR] CONJUGUÉS DE BIOMOLÉCULE
  申请人：CELGENE CORP

  公开号：WO2016090157A1

  公开（公告）日：2016-06-09

  The present invention relates to biomolecule conjugates which comprise a biomolecule wherein at least one non-natural amino acid (NNAA) is integral to the structure of the biomolecule and wherein the NNAA is a point of attachment of a linker to which a payload, particularly a cytotoxic agent, is attached. More specifically, this invention relates to conjugates of cell-binding agents and active release products comprising cytotoxic agents wherein the conjugates are produced by means of a cycloaddition reaction. Methods of production, pharmaceutical compositions and methods of use are provided.

  本发明涉及生物分子共轭物，其包括一种生物分子，其中至少有一种非天然氨基酸（NNAA）构成生物分子的结构，并且NNAA是连接物的附着点，连接物上附着有一种荷载物，特别是细胞毒性药剂。更具体地说，本发明涉及细胞结合剂和活性释放产物的共轭物，其中共轭物是通过环加成反应制备的。提供了生产方法、药物组合物和使用方法。