4-[2-[(E)-2-[(3E)-2-(4-carboxyphenyl)sulfanyl-3-[(2E)-2-[1,1-dimethyl-3-(4-sulfobutyl)benzo[e]indol-2-ylidene]ethylidene]cyclohexen-1-yl]ethenyl]-1,1-dimethylbenzo[e]indol-3-ium-3-yl]butane-1-sulfonate | 1345697-56-4

• 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: 4-[2-[(E)-2-[(3E)-2-(4-carboxyphenyl)sulfanyl-3-[(2E)-2-[1,1-dimethyl-3-(4-sulfobutyl)benzo[e]indol-2-ylidene]ethylidene]cyclohexen-1-yl]ethenyl]-1,1-dimethylbenzo[e]indol-3-ium-3-yl]butane-1-sulfonate
• CAS: 1345697-56-4；1355003-74-5
• 化学式: C₅₃H₅₆N₂O₈S₃
• 分子量: 945.234
• InChiKey: FSYOCUZIPREDHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  66
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  197
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-[2-[(E)-2-[(3E)-2-(4-carboxyphenyl)sulfanyl-3-[(2E)-2-[1,1-dimethyl-3-(4-sulfobutyl)benzo[e]indol-2-ylidene]ethylidene]cyclohexen-1-yl]ethenyl]-1,1-dimethylbenzo[e]indol-3-ium-3-yl]butane-1-sulfonate 、 在 三氟乙酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以35%的产率得到
  参考文献：
  名称：

  光敏剂 (PS)-花青染料 (CD) 缀合物：连接 PS 和 CD 部分的影响及其在肿瘤摄取和光动力治疗 (PDT) 中的方向

  摘要：

  研究连接光敏剂 HPPH [3-(1'-己氧基)乙基-3-脱乙烯基焦脱镁叶绿酸-a] 和花青染料 (CD) 在肿瘤成像和光动力治疗（双功能药物）中的影响，合成了一系列HPPH-CD缀合物。进行这些修改是为了尽量减少两个发色团之间的福斯特共振能量转移 (FRET) 并最大限度地增加单线态氧的产生。在含有可变长度接头的缀合物中，HPPH-CD缀合物（其中光敏剂（PS）和CD通过四个碳[(CH 2 ) 4 ]单元连接）表现出更高的肿瘤摄取、改善的肿瘤对比度和有限的皮肤摄取裸鼠中携带 Colon-26 (BALB/c) 或 U87 肿瘤的小鼠。HPPH 连接在苯基取代的 CD 5、6和7的间位上的双功能药物比相应的对位取代的类似物2、3和4表现出更长的肿瘤反应（治愈） ，这表明缀合物内 PS 和 CD 部分的方向也对肿瘤特异性产生显着差异。与 HPPH 相比，所有 HPPH-CD 缀合物的单线态氧

  DOI：

  10.1016/j.ejmech.2016.06.045
• 作为产物：
  描述：

  1,1,2-三甲基-3-(4-硫代丁基)苯并[e]吲哚鎓内盐 在 sodium acetate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 4-[2-[(E)-2-[(3E)-2-(4-carboxyphenyl)sulfanyl-3-[(2E)-2-[1,1-dimethyl-3-(4-sulfobutyl)benzo[e]indol-2-ylidene]ethylidene]cyclohexen-1-yl]ethenyl]-1,1-dimethylbenzo[e]indol-3-ium-3-yl]butane-1-sulfonate
  参考文献：
  名称：

  CYANINE DYE COMPOUND AND PREPARATION METHOD THEREFOR, AND DUAL-FUNCTION AGENT FOR PHOTODYNAMIC THERAPY AND PREPARATION METHOD THEREFOR

  摘要：

  公开号：

  EP2940021B1

文献信息

• Regioselective Synthesis and Photophysical and Electrochemical Studies of 20-Substituted Cyanine Dye-Purpurinimide Conjugates: Incorporation of Ni^IIinto the Conjugate Enhances its Tumor-Uptake and Fluorescence-Imaging Ability
  作者：Manivannan Ethirajan、Ping Chen、Tymish Y. Ohulchanskyy、Lalit N. Goswami、Anurag Gupta、Avinash Srivatsan、Mahabeer P. Dobhal、Joseph R. Missert、Paras N. Prasad、Karl M. Kadish、Ravindra K. Pandey

  DOI：10.1002/chem.201203867

  日期：2013.5.17

  approach to the synthesis of a variety of meso‐substituted purpurinimides. The reaction of meso‐substituted purpurinimide with N‐bromosuccinimide regioselectively introduced a bromo functionality at the 20‐position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso‐substituted analogues. Interestingly, the free base and the metalated

  我们在这里报告了一种简单有效的方法来合成各种内消旋取代的紫嘌呤亚胺。的反应内消旋-取代紫红素与Ñ溴代琥珀酰亚胺区域选择性引入到20位，将其用各种Suzuki反应条件下，硼酸进一步反应得到相应的溴功能内消旋取代的类似物。有趣的是，游离碱和金属化类似物在光敏功效（PDT）和肿瘤成像能力方面显示出显着差异。例如，游离碱偶联物在体外具有显着的PDT功效，但在荷瘤小鼠中肿瘤亲和力有限，而相应的Ni II该衍生物不会产生任何细胞杀伤作用，但在注射后24、48和72 h，以0.3μmolkg -1的剂量显示出优异的肿瘤成像能力。Ni II类似物的PDT功效有限可能是由于其无法产生单线态氧，而单线态氧是PDT中杀死细胞所需的关键细胞毒剂。根据DMSO中的电化学和光谱电化学数据，游离碱和相应的Ni II的第一次单电子氧化（0.52 V vs. SCE）和第一次单电子还原（-0.57-0.67 V vs. S
• Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes
  作者：Nayan J. Patel、Ethirajan Manivannan、Penny Joshi、Tymish J. Ohulchanskyy、Roger R. Nani、Martin J. Schnermann、Ravindra K. Pandey

  DOI：10.1111/php.12482

  日期：2015.9

  AbstractThis report presents a simple strategy to introduce various functionalities in a cyanine dye (bis‐indole‐N‐butylsulfonate‐polymethine bearing a fused cyclic chloro‐cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino‐phenyl thioether group attached to a cyclohexene ring system and the two N‐butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor‐avid CD provides an opportunity to create multi‐imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed.
• Synthesis, Photophysical, Electrochemical, Tumor-Imaging, and Phototherapeutic Properties of Purpurinimide-<i>N</i>-substituted Cyanine Dyes Joined with Variable Lengths of Linkers
  作者：Michael P. A. Williams、Manivannan Ethirajan、Kei Ohkubo、Ping Chen、Paula Pera、Janet Morgan、William H. White、Masayuki Shibata、Shunichi Fukuzumi、Karl M. Kadish、Ravindra K. Pandey

  DOI：10.1021/bc200345p

  日期：2011.11.16

  Purpurinimide methyl esters, bearing variable lengths of N-substitutions, were conjugated individually to a cyanine dye with a carboxylic acid functionality. The results obtained from in vitro and in vivo studies showed a significant impact of the linkers joining the phototherapeutic and fluorescence imaging moieties. The photosensitizer-fluorophore conjugate with a PEG linker showed the highest uptake in the liver, whereas the conjugate linked with two carbon units showed excellent tumor-imaging and PDT efficacy at 24 h postinjection. Whole body imaging and biodistribution studies at variable time points portrayed enhanced fluorescent uptake of the conjugates in the tumor compared to that in the skin. Interestingly, the conjugate with the shortest linker and the one joining with two carbon units showed faster clearance from normal organs, e.g., the liver, kidney, spleen, and lung, compared to that in tumors. Both imaging and PDT efficacy of the conjugates were performed in BALB/c mice bearing Colon26 tumors. Compared to the others, the short linker conjugate showed poor tumor fluorescent properties and as a corollary does not exhibit the dual functionality of the photosensitizer-fluorophore conjugate. For this reason, it was not evaluated for in vivo PDT efficacy. However, in Colon26 tumor cells (in vitro), the short linker was highly effective. Among the conjugates with variable linkers, the rate of energy transfer from the purpurinimide moiety to the cyanine moiety increased with deceasing linker length, as examined by femtosecond laser flash photolysis measurements. No electron transfer from the purpurinimide moiety to the singlet excited state of the cyanine moiety or from the singlet excited state of the cyanine moiety to the purpurinimide moiety occurred as indicated by a comparison of transient absorption spectra with spectra of the one-electron oxidized and one-electron reduced species of the conjugate obtained by spectroelectrochemical measurements.