acid chloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: acid chloride
• 英文别名: 4,4'-[1,5-pentanediylbis(oxy)]-bis[(5-methoxy-2-nitro)-benzoic acid chloride]；4-[5-(4-Carbonochloridoyl-2-methoxy-5-nitrophenoxy)pentoxy]-5-methoxy-2-nitrobenzoyl chloride；4-[5-(4-carbonochloridoyl-2-methoxy-5-nitrophenoxy)pentoxy]-5-methoxy-2-nitrobenzoyl chloride
• 化学式: C₂₁H₂₀Cl₂N₂O₁₀
• 分子量: 531.303
• InChiKey: NTSUWUWUXXMFBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  163
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  acid chloride 在 镍 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 4.0h， 生成 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine]
  参考文献：
  名称：

  Linker Length Modulates DNA Cross-Linking Reactivity and Cytotoxic Potency of C8/C8‘ Ether-Linked C2-exo-Unsaturated Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Dimers

  摘要：

  A C2/C2'-exo-unsaturated pyrrolo [2, 1-c] [1,4]benzodiazepine (PBD) dimer 4b (DRG-16) with a C8-O(CH2)(n)O-C8' diether linkage (n = 5) has been synthesized that shows markedly superior in vitro cytotoxic potency (e.g., > 3400-fold in IGROV1 ovarian cells) and interstrand DNA cross-linking reactivity (> 10-fold) compared to the shorter homologue 4a (SJG-136; n = 3). In contrast, for the C-ring unsubstituted series, the corresponding n = 5 dimer (3c) is generally less cytotoxic and has a lower interstrand cross-linking reactivity compared to its shorter n = 3 homologue (3a). Dimer 4b cross-links DNA with > 10-fold efficiency compared to 4a, and also inhibits the activity of the restriction endonuclease BamH1 more efficiently than either 3a or 4a. The C2-exo-unsaturated PBD dimers 4a,b are not only more effective than their C-ring saturated counterparts in terms of induced DeltaT(m) shift, but they also exert this effect more rapidly. Thus, while 3a and 3c exert 68 and 35% of their maximum effect immediately upon interaction with DNA, this level increases to 76 and 97% for 4a and 4b, respectively. Molecular modeling shows a rank order of 4b (n = 5) > 4a (n = 3) > 3a (n = 3) > 3c (n = 5) in terms of binding energy toward duplexes containing embedded target 5'-GAT(1-2)C cross-link sequences, reflecting the superior fit of the C2-exo-unsaturated rather than saturated C-rings of the PBD dimers. A novel synthesis of core synthetic building blocks for PBD dimers via stepwise Mitsunobu reaction and nitration with Cu(NO3)(2) is also reported.

  DOI：

  10.1021/jm030897l
• 作为产物：
  描述：

  1',3'-bis(4-carboxy-2-methoxy-5-nitrophenoxy)propane 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 acid chloride
  参考文献：
  名称：

  INTERMEDIATES USEFUL FOR THE SYNTHESIS OF PYRROLOBENZODIAZEPINES

  摘要：

  具有化学式（I）的化合物：基本上不含有任何具有化学式（IB）的相应化合物；制备这类化合物的方法，以及这类化合物的进一步转化。

  公开号：

  US20130035484A1

文献信息

• [EN] INTERMEDIATES USEFUL FOR THE SYNTHESIS OF PYRROLOBENZODIAZEPINES<br/>[FR] INTERMÉDIAIRES UTILES POUR LA SYNTHÈSE DE PYRROLOBENZODIAZÉPINES
  申请人：SPIROGEN LTD

  公开号：WO2011128650A1

  公开（公告）日：2011-10-20

  A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds.

  具有式（I）的化合物：基本上不含有式（IB）对应的任何化合物；制备这种化合物的方法，以及这种化合物的进一步转化。
• [EN] PYRROLOBENZODIAZEPINE CONJUGATES<br/>[FR] CONJUGUÉS DE PYRROLOBENZODIAZÉPINE
  申请人：MEDIMMUNE LTD

  公开号：WO2018192944A1

  公开（公告）日：2018-10-25

  A compound of formula I and salts and solvates thereof, wherein: R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR', nitro, Me3Sn and halo; where R and R' are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR', nitro, Me3Sn and halo; R" is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, NRN2 (where RN2 is H or C1-4 alkyl), and/or aromatic rings, e.g. benzene or pyridine; Y and Y' are selected from O, S, or NH; R6, R7, R9 are selected from the same groups as R6, R7 and R9 respectively; R11b is selected from OH, ORA, where RA is C1-4 alkyl; and RL is a linker for connection to a cell binding agent.

  化合物I的结构式及其盐和溶剂化合物，其中：R6和R9分别选自H、R、OH、OR、SH、SR、NH2、NHR、NRR'、硝基、Me3Sn和卤素；其中R和R'分别选自可选择取代的C1-12烷基、C3-20杂环烷基和C5-20芳基；R7选自H、R、OH、OR、SH、SR、NH2、NHR、NRR'、硝基、Me3Sn和卤素；R"是C3-12烷基基团，该链可被一个或多个杂原子（例如O、S、NRN2（其中RN2为H或C1-4烷基））和/或芳香环（例如苯或吡啶）中断；Y和Y'选自O、S或NH；R6、R7、R9分别选自与R6、R7和R9相同的基团；R11b选自OH、ORA，其中RA为C1-4烷基；RL是用于连接到细胞结合剂的连接剂。
• [EN] PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES<br/>[FR] CONJUGUÉS ANTICORPS-PYRROLOBENZODIAZÉPINE
  申请人：SPIROGEN SARL

  公开号：WO2015052535A1

  公开（公告）日：2015-04-16

  Conjugates of specific PBD dimers with an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.

  将特定PBD二聚体与结合到CD22的抗体结合，该抗体包括具有根据SEQ ID NO. 1序列的VH结构域。
• [EN] PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES<br/>[FR] CONJUGUÉS ANTICORPS-PYRROLOBENZODIAZÉPINES
  申请人：SPIROGEN SARL

  公开号：WO2015052532A1

  公开（公告）日：2015-04-16

  Conjugates of specific PBD dimers with an antibody that binds to PSMA, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 3, 5, 7, 8, 9, or 10, optionally further comprising a VL domain having the sequence 5 according to any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.

  将特定PBD二聚体与结合到PSMA的抗体结合，该抗体包括具有根据SEQ ID NOs之一的序列的VH结构域，选择性地进一步包括具有根据SEQ ID NOs之一的序列的VL结构域。 2, 4, 6, 11, 12, 13, 14, 15, 16, 17或18。
• [EN] ANTIBODIES AND ANTIBODY-DRUG CONJUGATES<br/>[FR] ANTICORPS ET CONJUGUÉS ANTICORPS-MÉDICAMENT
  申请人：MEDIMMUNE LTD

  公开号：WO2015155345A1

  公开（公告）日：2015-10-15

  This application provides antibodies and antigen binding fragments thereof which are capable of specifically binding the 5T4 cell surface antigen, antibody-drug conjugates, and antibody-imaging agent conjugates, as well as means and methods for producing and using them.

  该应用程序提供了能够特异性结合5T4细胞表面抗原、抗体药物偶联物以及抗体成像剂偶联物的抗体及其抗原结合片段，以及生产和使用它们的方法和手段。