2,5-bis<<5-(benzyloxycarbonyl)-3-<2-(methoxycarbonyl)ethyl>-4-methylpyrrol-2-yl>methyl>-3,4-diethylpyrrole | 149365-59-3

• 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: 2,5-bis<<5-(benzyloxycarbonyl)-3-<2-(methoxycarbonyl)ethyl>-4-methylpyrrol-2-yl>methyl>-3,4-diethylpyrrole
• 英文别名: Dibenzyl 5,5'-[(3,4-diethyl-1H-pyrrole-2,5-diyl)bis(methylene)]bis[4-(3-methoxy-3-oxopropyl)-3-methyl-1H-pyrrole-2-carboxylate]；benzyl 5-[[3,4-diethyl-5-[[3-(3-methoxy-3-oxopropyl)-4-methyl-5-phenylmethoxycarbonyl-1H-pyrrol-2-yl]methyl]-1H-pyrrol-2-yl]methyl]-4-(3-methoxy-3-oxopropyl)-3-methyl-1H-pyrrole-2-carboxylate
• CAS: 149365-59-3
• 化学式: C₄₄H₅₁N₃O₈
• 分子量: 749.904
• InChiKey: JALCMIKHVMIZKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  55
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,5-bis<<5-(benzyloxycarbonyl)-3-<2-(methoxycarbonyl)ethyl>-4-methylpyrrol-2-yl>methyl>-3,4-diethylpyrrole 以76的产率得到benzyl 5-[[3,4-diethyl-5-[[3-(3-hydroxypropyl)-4-methyl-5-phenylmethoxycarbonyl-1H-pyrrol-2-yl]methyl]-1H-pyrrol-2-yl]methyl]-4-(3-hydroxypropyl)-3-methyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Radiation sensitization using texaphyrins

  摘要：

  Texaphyrins可用作放射敏化剂。 Texaphyrins作为放射敏化剂的优点包括：i）低氧化还原电位，使放射线诱导的水化电子流向texaphyrin而不是中和羟基自由基，从而使羟基自由基引起细胞损伤，ii）相对稳定的texaphyrin自由基，容易与相邻分子共价修饰，从而引起进一步的细胞损伤，iii）固有的生物定位，和iv）对O.sub.2的存在或缺失不敏感。这些特性使得texaphyrins特别适用于治疗实体肿瘤的低氧区域。治疗患有肿瘤或动脉粥样硬化的个体的方法包括使用texaphyrin作为放射敏化剂和光动力治疗肿瘤的药物，或使用texaphyrin作为内部和外部电离辐射的药物。还提供了新型的texaphyrins。

  公开号：

  US05622946A1
• 作为产物：
  描述：

  benzyl 5-acetoxymethyl-4-(2-methoxycarbonylethyl)-3-methylpyrrole-2-carboxylate 、 3,4-二乙基吡咯 以61的产率得到2,5-bis<<5-(benzyloxycarbonyl)-3-<2-(methoxycarbonyl)ethyl>-4-methylpyrrol-2-yl>methyl>-3,4-diethylpyrrole
  参考文献：
  名称：

  Radiation sensitization using texaphyrins

  摘要：

  Texaphyrins可用作放射敏化剂。 Texaphyrins作为放射敏化剂的优点包括：i）低氧化还原电位，使放射线诱导的水化电子流向texaphyrin而不是中和羟基自由基，从而使羟基自由基引起细胞损伤，ii）相对稳定的texaphyrin自由基，容易与相邻分子共价修饰，从而引起进一步的细胞损伤，iii）固有的生物定位，和iv）对O.sub.2的存在或缺失不敏感。这些特性使得texaphyrins特别适用于治疗实体肿瘤的低氧区域。治疗患有肿瘤或动脉粥样硬化的个体的方法包括使用texaphyrin作为放射敏化剂和光动力治疗肿瘤的药物，或使用texaphyrin作为内部和外部电离辐射的药物。还提供了新型的texaphyrins。

  公开号：

  US05622946A1

文献信息

• Radiation sensitization using texaphyrins
  申请人：Pharmacyclics, Inc.

  公开号：US05622946A1

  公开（公告）日：1997-04-22

  Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

  Texaphyrins可用作放射敏化剂。 Texaphyrins作为放射敏化剂的优点包括：i）低氧化还原电位，使放射线诱导的水化电子流向texaphyrin而不是中和羟基自由基，从而使羟基自由基引起细胞损伤，ii）相对稳定的texaphyrin自由基，容易与相邻分子共价修饰，从而引起进一步的细胞损伤，iii）固有的生物定位，和iv）对O.sub.2的存在或缺失不敏感。这些特性使得texaphyrins特别适用于治疗实体肿瘤的低氧区域。治疗患有肿瘤或动脉粥样硬化的个体的方法包括使用texaphyrin作为放射敏化剂和光动力治疗肿瘤的药物，或使用texaphyrin作为内部和外部电离辐射的药物。还提供了新型的texaphyrins。
• Texaphyrin metal complexes having improved functionalization
  申请人：Board of Regents, University of TX

  公开号：US05599923A1

  公开（公告）日：1997-02-04

  Texaphyrin metal complexes having improved functionalization including the addition of electron donating groups to positions 12, 15, 18 and/or 21 and/or the addition of electron withdrawing groups to positions 15 or 18 of the macrocycle. Electron donating groups at positions 12, 15, 18 and/or 21 contribute electrons to the aromatic .pi. system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis, these texaphyrin metal complexes having enhanced stability are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic tumor therapy and applications requiring singlet oxygen production for cytotoxicity. Electron withdrawing groups at positions 15 or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential are useful for radiosensitization applications.

  Texaphyrin金属配合物具有改进的功能化，包括在大环的12、15、18和/或21号位置添加电子供体基团和/或在15或18号位置添加电子受体基团。在12、15、18和/或21号位置的电子供体基团为大环的芳香π系统提供电子，从而稳定金属配合物以防止脱金属化和亚胺键水解，这些具有增强稳定性的Texaphyrin金属配合物可用于定位、磁共振成像、放射增敏、放射治疗、荧光成像、光动力治疗和需要产生单线态氧以进行细胞毒性的应用。在15或18号位置的电子受体基团使大环更容易还原，即氧化还原电位更低，大环更容易获得电子形成自由基。这种具有低氧化还原电位的Texaphyrin金属配合物可用于放射增敏应用。
• Texaphyrin compounds having improved functionalization
  申请人：Pharmacyclics, Inc.

  公开号：US05599928A1

  公开（公告）日：1997-02-04

  Texaphyrin metal complexes having improved functionalization include the addition of electron-donating groups to positions 2, 7, 12, 15, 18 and/or 21 and/or the addition of electron-withdrawing groups to positions 15 and/or 18 of the macrocycle. Electron-donating groups at positions 2, 7, 12, 15, 18 and/or 21 contribute electrons to the aromatic .pi. system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis. The addition of substituents to the 12 and 21 positions of the macrocycle offer steric protection for the imine bonds against possible in vivo enzyme hydrolysis. Electron-withdrawing groups at positions 15 and/or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential and imine bond stabilization are useful in a variety of applications.

  含有改进功能的Texaphyrin金属配合物包括在大环上的位置2、7、12、15、18和/或21处添加电子供体基团和/或在位置15和/或18处添加电子受体基团。在位置2、7、12、15、18和/或21处的电子供体基团为大环的芳香π体系提供电子，从而稳定金属配合物以防止脱金属和亚胺键水解。在大环的12和21位置添加取代基可为亚胺键提供立体保护，以防止可能发生的体内酶水解。在位置15和/或18处的电子受体基团使大环更容易被还原，即氧化还原电位更低，大环更容易获得电子形成自由基。具有低氧化还原电位和亚胺键稳定性的Texaphyrin在各种应用中非常有用。
• Methods of MRI enhancement using compounds having improved
  申请人：Pharmacyclics, Inc.

  公开号：US05601802A1

  公开（公告）日：1997-02-11

  Texaphyrin metal complexes having improved functionalization include the addition of electron-donating groups to positions 2, 7, 12, 15, 18 and/or 21 and/or the addition of electron-withdrawing groups to positions 15 and/or 18 of the macrocycle. Electron-donating groups at positions 2, 7, 12, 15, 18 and/or 21 contribute electrons to the aromatic .pi. system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis. These texaphyrin metal complexes having enhanced stability are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic therapy, RNA hydrolysis, DNA photocleavage, and applications requiring singlet oxygen production for cytotoxicity. Electron-withdrawing groups at positions 15 and/or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential are useful for radiation sensitization applications.

  Texaphyrin金属配合物的改进功能化包括在大环的2、7、12、15、18和/或21位添加电子给予基团，以及在15和/或18位添加电子吸引基团。在2、7、12、15、18和/或21位的电子给予基团向大环的芳香π系统提供电子，从而稳定金属配合物，使其不易去金属化并使亚胺键不易水解。这些具有增强稳定性的Texaphyrin金属配合物可用于定位、磁共振成像、放射增敏、放射治疗、荧光成像、光动力疗法、RNA水解、DNA光解和需要产生单线态氧以达到细胞毒性的应用。在15和/或18位的电子吸引基团使大环更容易还原，即其氧化还原电位更低，大环更容易获得电子形成自由基。这种具有低氧化还原电位的Texaphyrins可用于放射增敏应用。
• Water soluble texaphyrin metal complexes for viral deactivation
  申请人：Board of Regents, The University of Texas System

  公开号：US05432171A1

  公开（公告）日：1995-07-11

  The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.

  本发明涉及水溶性的羟基取代的四苯卟啉类化合物，保留了亲脂性，以及这些化合物的合成和用途。这些扩展的卟啉类大环分子是二价和三价金属离子的高效螯合剂。本发明的羟基取代的四苯卟啉衍生物的各种金属（如过渡金属、主族金属和镧系金属）配合物具有异常的水溶性和稳定性。它们在生理重要区域（即690-880nm）强烈吸收光线。它们具有增强的弛豫度，因此在磁共振成像中很有用。它们形成高产率的长寿命三重态，并作为光敏剂生成单重氧。因此，它们对于灭活或破坏人类免疫缺陷病毒（HIV-1）、单核或其他感染该病毒的细胞以及肿瘤细胞非常有用。它们水溶性，但保留足够的亲脂性，以便更具亲和力地结合到富含脂质的区域，如动脉粥样硬化和肿瘤。它们可用于磁共振成像后的光动力学肿瘤治疗，用于动脉粥样硬化和肿瘤的治疗。这些特性，加上它们的高化学稳定性和可溶性，增加了它们的实用性。