(S)-2-((S)-2-氨基-3-苯基丙酰胺基)-N-(4-(羟甲基)苯基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酰胺 | 159857-64-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-2-((S)-2-氨基-3-苯基丙酰胺基)-N-(4-(羟甲基)苯基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酰胺
• 英文名称: (S)-2-((S)-2-amino-3-phenyl-propionylamino)-6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-hexanoic acid (4-hydroxymethyl-phenyl)-amide
• 英文别名: Phe-Lys(MMT)-PAB-OH；Phe-Lys(MMT)-PABOH；(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanamide
• CAS: 159857-64-4
• 化学式: C₄₂H₄₆N₄O₄
• 分子量: 670.852
• InChiKey: VLSKQONNNJIFRJ-YDAXCOIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  126
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-((S)-2-氨基-3-苯基丙酰胺基)-N-(4-(羟甲基)苯基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酰胺 在 molecular sieve 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 Carbonic acid 4-((S)-2-{(S)-2-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexanoylamino]-3-phenyl-propionylamino}-6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-hexanoylamino)-benzyl ester 4-nitro-phenyl ester
  参考文献：
  名称：

  Monomethoxytrityl (MMT) as a versatile amino protecting group for complex prodrugs of anticancer compounds sensitive to strong acids, bases and nucleophiles

  摘要：

  Cathepsin B-sensitive maleimidocaproyl-Phe-Lys linker compounds containing acid-sensitive anticancer drugs doxorubicin, mitomycin C and paclitaxel (taxol(R)) attached through a self-immolative p-aminobenzylcarbonyl spacer were prepared using monomethoxytrityl (MMT) as the amino protecting group for Lys. MMT could be removed cleanly and in high yield by dichloroacetic and chloroacetic acids in the presence of anisole with minimal workup. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01158-1
• 作为产物：
  描述：

  (S)-2-((((9h-芴-9-基)甲氧基)羰基)氨基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酸 在 lithium hydroxide 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 二乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 (S)-2-((S)-2-氨基-3-苯基丙酰胺基)-N-(4-(羟甲基)苯基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酰胺
  参考文献：
  名称：

  Monomethoxytrityl (MMT) as a versatile amino protecting group for complex prodrugs of anticancer compounds sensitive to strong acids, bases and nucleophiles

  摘要：

  Cathepsin B-sensitive maleimidocaproyl-Phe-Lys linker compounds containing acid-sensitive anticancer drugs doxorubicin, mitomycin C and paclitaxel (taxol(R)) attached through a self-immolative p-aminobenzylcarbonyl spacer were prepared using monomethoxytrityl (MMT) as the amino protecting group for Lys. MMT could be removed cleanly and in high yield by dichloroacetic and chloroacetic acids in the presence of anisole with minimal workup. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01158-1

文献信息

• Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites
  申请人：Govindan Serengulam V.

  公开号：US20080171067A1

  公开（公告）日：2008-07-17

  The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

  本发明涉及将治疗剂递送到目标细胞、组织或生物体的方法和组合物。在优选的实施例中，治疗剂以负载治疗剂的聚合物形式递送，该聚合物可能包含一个或多个治疗剂的许多拷贝。在更优选的实施例中，聚合物可以与含有一种或多种半抗原的肽部分结合，例如HSG。例如，通过使用双特异性或多特异性抗体或片段的预定位技术，将治疗剂-聚合物-肽复合物递送到目标细胞，该抗体或片段至少有一个结合臂识别半抗原，并且至少有第二个结合臂特异性地结合到与疾病或病原体相关的抗原，例如肿瘤相关抗原。本发明提供了合成和使用此类负载治疗剂的聚合物及其缀合物的方法。
• Small molecule conjugates for intracellular delivery of nucleic acids
  申请人：Hoffmann-La Roche Inc.

  公开号：US09198947B2

  公开（公告）日：2015-12-01

  The invention provides use of novel compounds for delivery of nucleic acids, and conjugates of these compounds with nucleic acids. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to said compounds and co-administered with a delivery polymer to achieve mRNA knock down in vivo are disclosed therein.

  本发明提供了用于核酸传递的新颖化合物的使用，以及这些化合物与核酸的偶联物。进一步披露了在共价连接到所述化合物并与传递聚合物共给药以实现体内mRNA敲低时特别有用的化学稳定化siRNA的新颖设计标准。
• Facile synthesis of maleimide bifunctional linkers
  作者：H.Dalton King、Gene M Dubowchik、Michael A Walker

  DOI：10.1016/s0040-4039(02)00192-2

  日期：2002.3

  The synthesis of maleimide containing derivatives capable of serving as linkers for the conjugation of proteins is described. These compounds differ from previously reported linkers by having multiple sites available for drug attachment. Compounds 3a, 3b, and 3d were synthesized from the corresponding amino alcohols by the addition of two equivalents of t-butyl bromoacetate to a series of amino alcohols

  描述了含有马来酰亚胺的衍生物的合成，该衍生物能够用作蛋白质缀合的连接体。这些化合物与先前报道的接头不同，其具有多个可用于药物附着的位点。通过将两当量的溴乙酸叔丁酯添加到一系列氨基醇中，然后在Mitsunobu反应条件下引入马来酰亚胺并进行酯水解，由相应的氨基醇合成化合物3a，3b和3d。
• Small molecule conjugates for intracellular delivery of biologically active compounds
  申请人：Hoffmann-La Roche Inc.

  公开号：US20140135381A1

  公开（公告）日：2014-05-15

  The invention provides novel compounds and conjugates of these compounds useful for the delivery of biologically active substances. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to a delivery polymer to achieve in vivo mRNA knock down are disclosed therein.

  本发明提供了新型化合物及其共轭物，用于传递生物活性物质。本发明还揭示了化学稳定的siRNA的新设计标准，特别是当与传递聚合物共价连接以实现体内mRNA敲下时，这些标准非常有用。
• Synthesis of an immunoconjugate of camptothecin
  作者：Michael A Walker、Gene M Dubowchik、Sandra J Hofstead、Pamela A Trail、Raymond A Firestone

  DOI：10.1016/s0960-894x(01)00707-7

  日期：2002.1

  The first immunoconjugate of camptothecin has been synthesized wherein the drug is attached to the tumor-recognizing antibody BR96 via a Cathepsin B cleavable linker. Endocytosis of the immunoconjugate upon binding to the tumor cell followed by enzymatic cleavage of the linker inside the endosome ensures tumor-specific release of the drug. In this way, it is hoped that the dose-limiting side effects associated with camptothecin can be eliminated while the antitumor activity is preserved. (C) 2002 Elsevier Science Ltd. All rights reserved.