(S)-2-amino-6-((4-methoxyphenyl)diphenylmethyl-amino)hexanoic acid | 159857-61-1

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-2-amino-6-((4-methoxyphenyl)diphenylmethyl-amino)hexanoic acid
• 英文别名: H-Lys(MMT)-OH；Lys(MMT)；L-Lysine, N6-[(4-methoxyphenyl)diphenylmethyl]-；(2S)-2-amino-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanoic acid
• CAS: 159857-61-1
• 化学式: C₂₆H₃₀N₂O₃
• 分子量: 418.536
• InChiKey: QSAUHWWUFRQEMX-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-6-((4-methoxyphenyl)diphenylmethyl-amino)hexanoic acid 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 37.0h， 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
• 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 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以97%的产率得到(S)-2-amino-6-((4-methoxyphenyl)diphenylmethyl-amino)hexanoic acid
  参考文献：
  名称：

  [EN] POLYCONJUGATES FOR DELIVERY OF RNAI TRIGGERS TO TUMOR CELLS IN VIVO
  [FR] POLYCONJUGUÉS POUR L'ADMINISTRATION DE DÉCLENCHEURS D'ARNI À DES CELLULES TUMORALES IN VIVO

  摘要：

  本发明涉及将RNA干扰（RNAi）触发物传递至体内整合素阳性肿瘤细胞的组合物。这些组合物包括以RGD配体为靶向的两性膜活性多胺，可逆地修饰为酶可切割二肽-酰胺基苄-碳酸酯掩蔽剂。修饰掩盖了聚合物的膜活性，而可逆性提供了生理响应性。这些可逆修饰的多胺（动态多共轭物或共轭物）进一步与RNAi触发物共价连接。

  公开号：

  WO2015021092A1

文献信息

• Cobalamin conjugates for anti-tumor therapy
  申请人：Weinshenker M. Ned

  公开号：US20050054607A1

  公开（公告）日：2005-03-10

  The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.

  本发明提供了一种适用于治疗肿瘤相关疾病的钴胺素-药物结合物。钴胺素通过可切割的连接剂间接共价结合到抗肿瘤药物上，还可以通过一个或多个可选的间隔物。钴胺素通过其核糖环的5'-OH与第一间隔物或可切割连接剂共价结合。药物通过其现有或添加的功能基团与可切割连接剂的第二间隔物结合。在给药后，结合物与转钴胺素（其任何同工异构体）形成复合物。然后，该复合物结合到细胞膜上的受体并被细胞摄取。一旦进入细胞，细胞内酶将切割结合物，从而释放药物。根据结合物的结构，特定类别或类型的细胞内酶影响切割。由于生长细胞对钴胺素的需求量较高，肿瘤细胞通常摄取结合物的比例高于正常非生长细胞。本发明的结合物与相应的游离药物相比，具有较低的全身毒性和增强的疗效。
• 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。
• Cobalamin Taxane Bioconjugates For Treating Eye Disease
  申请人：Gebhard John R.

  公开号：US20120053144A1

  公开（公告）日：2012-03-01

  The present invention is directed to methods of treating eye disease. In one embodiment, the method can comprise administering a bioconjugate to a subject to treat the eye disease, where the bioconjugate comprises a taxane covalently bonded to a cobalamin. Additionally, the bioconjugate can be dissolved in an aqueous solution prior to administration.

  本发明涉及治疗眼部疾病的方法。在一种实施例中，该方法可以包括向受试者施用生物共轭物以治疗眼部疾病，其中该生物共轭物包括共价键合的紫杉醇和钴胺素。此外，在施用前，该生物共轭物可以溶解在水溶液中。
• In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages
  申请人：Rozema David B.

  公开号：US20120172412A1

  公开（公告）日：2012-07-05

  The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

  本发明涉及用于体内RNA干扰（RNAi）多核苷酸递送到细胞的组合物。该组合物包括具有酶可切割二肽酰胺苯甲酰碳酸酯掩蔽剂的两性亲媒膜活性多胺可逆修饰。修饰掩蔽了聚合物的膜活性，而可逆性提供了生理响应性。可逆修饰的多胺（动态多共轭物或DPC）进一步与RNAi多核苷酸共价连接或与靶向RNAi多核苷酸靶向分子共轭物共同给药。
• 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。