IR-783 | 1200441-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: IR-783
• 英文别名: 4-[(2E)-2-[(2E)-2-[2-chloro-3-[(E)-2-[3,3-dimethyl-1-(4-sulfonatobutyl)indol-1-ium-2-yl]ethenyl]cyclohex-2-en-1-ylidene]ethylidene]-3,3-dimethylindol-1-yl]butane-1-sulfonate
• CAS: 1200441-54-8
• 化学式: C₃₈H₄₆ClN₂O₆S₂
• 分子量: 726.378
• InChiKey: HDEMJFRQENFOCB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  137
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  IR-783 、 4-氨基丁酸 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以41%的产率得到
  参考文献：
  名称：

  基于氨基花青素独特光谱特性的近红外比率荧光探针分子设计策略

  摘要：

  尽管各种近红外（NIR）荧光团可广泛用作标记试剂，但几乎没有功能性NIR荧光探针在与生物分子发生特定反应后吸收和/或荧光光谱发生变化。广泛使用的光致电子转移机制不适用于NIR荧光团，例如三碳菁，因为它们的长激发波长会产生较小的单重态激发能。我们已经报道了胺取代的三碳菁的独特光谱特性，这些光谱特性被用于开发两种设计策略。一种方法是通过利用与生物分子发生特定反应前后的供电子能力差异来控制吸收波长，另一种方法是基于通过在酸性条件下吸收变化而引起的重叠积分变化来调节福斯特共振能量转移效率，从而控制荧光强度。这些策略已通过获得基于三碳花青的比例NIR荧光探针用于酯酶和pH值进行了验证。

  DOI：

  10.1002/chem.200900035
• 作为产物：
  描述：

  N-[(3-(苯胺基亚甲基)-2-氯-1-环己烯-1-基)亚甲基]苯胺盐酸盐 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 IR-783 、 1-(5-carboxypentyl)-2-((E)-2-((E)-3-(2-((E)-1-(5-carboxypentyl)-3,3-dimethylindolin-2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-3H-indol-1-ium
  参考文献：
  名称：

  Improving Therapeutic Potential of Farnesylthiosalicylic Acid: Tumor Specific Delivery via Conjugation with Heptamethine Cyanine Dye

  摘要：

  The RAS and mTOR inhibitor S-trans-trans-famesylthiosalicylic acid (FTS) is a promising anticancer agent with moderate potency, currently undergoing clinical trials as a chemotherapeutic agent. FTS has displayed its potential against a variety of cancers including endocrine resistant breast cancer. However, the poor pharmacokinetics profile attributed to its high hydrophobicity is a major hindrance for its continued advancement in clinic. One of the ways to improve its therapeutic potential would be to enhance its bioavailability to cancer tissue by developing a method for targeted delivery. In the current study, FTS was conjugated with the cancer-targeting heptamethine cyanine dye 5 to form the FTS dye conjugate 11. The efficiency tumor targeting properties of conjugate 11 against cancer cell growth and mTOR inhibition was evaluated in vitro in comparison with parent FTS. Cancer targeting of 11 in a live mouse model of MCF7 xenografts was demonstrated with noninvasive, near infrared fluorescence (NIRF). imaging. The results from our studies clearly suggest that the bioavailability of FTS is indeed" improved as indicated by log P values and cancer cell uptake. The FTS dye conjugate 11 displayed higher potency (IC50 = 16.8 +/- 0.5 mu M) than parent FTS (IC50 = similar to 51.3 +/- 1.8 mu M) and inhibited mTOR activity in the cancer cells at a lower concentration (12.5 mu M). The conjugate 11 was shown to be specifically accumulated in tumors as observed by in vivo NIRF imaging, organ distribution, and ex vivo tumor histology along with cellular level confocal microscopy. In conclusion, the conjugation of FTS with cancer-targeting heptamethine cyanine dye improved its pharmacological profile.

  DOI：

  10.1021/acs.molpharmaceut.5b00906

文献信息

• A Cyanine Photooxidation/ <i>β</i> ‐Elimination Sequence Enables Near‐infrared Uncaging of Aryl Amine Payloads
  作者：Tsuyoshi Yamamoto、Donald R. Caldwell、Albert Gandioso、Martin J. Schnermann

  DOI：10.1111/php.13090

  日期：——

  amines. Heptamethine cyanines substituted with an aryl amine at the C4′ position undergo only inefficient release, likely due electronic factors. We then pursued the hypothesis that the carbonyl products derived from cyanine photooxidation could undergo efficient β‐elimination. After examining both symmetrical and unsymmetrical scaffolds, we identify a merocyanine substituted with indolenine and coumarin

  使用近红外波长的解笼锁策略可以在复杂的环境中实现生物分子的高度靶向传递。许多方法，包括我们使用花青光氧化开发的方法，仅限于含酚的有效载荷。鉴于胺在各种生物过程中的关键作用，我们试图使用花青光氧化来启动芳胺的释放。在 C4' 位置被芳胺取代的七次甲基花青只能进行低效释放，可能是由于电子因素。然后，我们假设花青光氧化产生的羰基产物可以进行有效的 β-消除。在检查了对称和非对称支架后，我们鉴定了一种被假吲哚和香豆素杂环取代的部花青，其经历了有效的光氧化和苯胺解笼锁。总的来说，这些研究提供了一种新的方案——花青光氧化然后β-消除——通过它来设计具有有效解笼锁特性的光笼。
• [EN] OPTICAL AGENTS FOR IMAGING AND VISUALIZATION OF MATRIX METALLOPROTEINASE ENZYMES<br/>[FR] AGENTS OPTIQUES PERMETTANT D'OBTENIR DES IMAGES DE MÉTALLOPROTÉASES MATRICIELLES ET DE LES VISUALISER
  申请人：MALLINCKRODT LLC

  公开号：WO2013039851A1

  公开（公告）日：2013-03-21

  The invention relates generally to optical agents for biomedical applications including imaging, visualization, phototherapy and diagnostic monitoring of cells and tissue expressing MMPs and/or tissues associated with the expression of MMPs. In some embodiments, for example, optical agents of the present invention selectively bind to, or otherwise preferentially associate with, a target tissue expressing one or more MMPs, and function to couple electromagnetic radiation into and/or out of the target tissue, for example via optical absorption, fluorescence, scattering and/or optoacoustic processes.

  该发明通常涉及用于生物医学应用的光学试剂，包括成像、可视化、光疗和诊断监测表达MMPs和/或与MMPs表达相关的细胞和组织。在某些实施例中，例如，本发明的光学试剂选择性地结合到或以其他方式优先与表达一个或多个MMPs的靶组织结合，并且功能是将电磁辐射耦合到和/或从靶组织中传出，例如通过光吸收、荧光、散射和/或光声过程。
• DRUG FRAGMENT IMAGING AGENT CONJUGATES
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20200390909A1

  公开（公告）日：2020-12-17

  Functional dyes and methods of use are provided. The dyes are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, particularly with oral administration of the dyes.

  本发明提供功能染料及其使用方法。这些染料可用于各种医学应用，包括但不限于诊断成像和治疗，内窥镜应用以检测肿瘤和其他异常情况，特别是通过口服染料。
• Elucidating the cellular uptake mechanisms of heptamethine cyanine dye analogues for their use as an anticancer drug‐carrier molecule for the treatment of glioblastoma
  作者：Elizabeth Cooper、Peter J. Choi、Kihwan Hwang、Kyung M. Nam、Chae‐Yong Kim、Tina Shaban、Patrick Schweder、Edward Mee、Jason Correia、Clinton Turner、Richard L. M. Faull、William A. Denny、Katsuya Noguchi、Mike Dragunow、Jiney Jose、Thomas I.‐H. Park

  DOI：10.1111/cbdd.14171

  日期：2023.3

  AbstractThe development of chemotherapies for glioblastoma is hindered by their limited bioavailability and toxicity on normal brain function. To overcome these limitations, we investigated the structure‐dependent activity of heptamethine cyanine dyes (HMCD), a group of tumour‐specific and BBB permeable near‐infrared fluorescent dyes, in both commercial (U87MG) and patient‐derived GBM cell lines. HMCD analogues with strongly ionisable sulphonic acid groups were not taken up by patient‐derived GBM cells, but were taken up by the U87MG cell line. HMCD uptake relies on a combination of transporter uptake through organic anion‐transporting polypeptides (OATPs) and endocytosis into GBM cells. The uptake of HMCDs was not affected by p‐glycoprotein efflux in GBM cells. Finally, we demonstrate structure‐dependent cytotoxic activity at high concentrations (EC50: 1–100 μM), likely due to mitochondrial damage‐induced apoptosis. An in vivo orthotopic glioblastoma model highlights tumour‐specific accumulation of our lead HMCD, MHI‐148, for up to 7 days following a single intraperitoneal injection. These studies suggest that strongly ionisable groups like sulphonic acids hamper the cellular uptake of HMCDs in patient‐derived GBM cell lines, highlighting cell line‐specific differences in HMCD uptake. We envisage these findings will help in the design and structural modifications of HMCDs for drug‐delivery applications for glioblastoma.
• Molecular Design Strategies for Near-Infrared Ratiometric Fluorescent Probes Based on the Unique Spectral Properties of Aminocyanines
  作者：Kazuki Kiyose、Sakiko Aizawa、Eita Sasaki、Hirotatsu Kojima、Kenjiro Hanaoka、Takuya Terai、Yasuteru Urano、Tetsuo Nagano

  DOI：10.1002/chem.200900035

  日期：2009.9.14

  In spite of the wide availability of various near‐infrared (NIR) fluorophores as labeling reagents, there are few functional NIR fluorescent probes for which change in the absorption and/or fluorescence spectra upon specific reaction with biomolecules is seen. The widely used photoinduced electron‐transfer mechanism is unsuitable for NIR fluorophores, such as tricarbocyanines, because their long excitation

  尽管各种近红外（NIR）荧光团可广泛用作标记试剂，但几乎没有功能性NIR荧光探针在与生物分子发生特定反应后吸收和/或荧光光谱发生变化。广泛使用的光致电子转移机制不适用于NIR荧光团，例如三碳菁，因为它们的长激发波长会产生较小的单重态激发能。我们已经报道了胺取代的三碳菁的独特光谱特性，这些光谱特性被用于开发两种设计策略。一种方法是通过利用与生物分子发生特定反应前后的供电子能力差异来控制吸收波长，另一种方法是基于通过在酸性条件下吸收变化而引起的重叠积分变化来调节福斯特共振能量转移效率，从而控制荧光强度。这些策略已通过获得基于三碳花青的比例NIR荧光探针用于酯酶和pH值进行了验证。