N-(tert-butoxycarbonyl)-N,β,β-trimethyl-L-phenylalanine-N-[(3S,4E)-6-ethoxy-2,5-dimethyl-6-oxohexa-4-ene-3-yl]-N,3-dimethyl-L-valinamide | 228266-39-5

• 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
• 英文名称: N-(tert-butoxycarbonyl)-N,β,β-trimethyl-L-phenylalanine-N-[(3S,4E)-6-ethoxy-2,5-dimethyl-6-oxohexa-4-ene-3-yl]-N,3-dimethyl-L-valinamide
• 英文别名: ethyl (S)-N-tert-butoxycarbonyl-N,β,β-trimethylphenylalanyl-(S)-tert-leucyl-(2E,4S)-N-methyl-4-amino-2,5-dimethylhex-2-enoate；ethyl (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-phenylbutanoyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoate
• CAS: 228266-39-5
• 化学式: C₃₄H₅₅N₃O₆
• 分子量: 601.827
• InChiKey: UCUGHLRPMCEWCW-ASDIUBQGSA-N

物化性质

• 沸点：
  702.6±60.0 °C(Predicted)
• 密度：
  1.052±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-N,β,β-trimethyl-L-phenylalanine-N-[(3S,4E)-6-ethoxy-2,5-dimethyl-6-oxohexa-4-ene-3-yl]-N,3-dimethyl-L-valinamide 在 lithium hydroxide 、 水 、 柠檬酸 作用下， 以 甲醇 为溶剂， 反应 28.0h， 生成 (6S,9S,12S,E)-9-tert-butyl-12-isopropyl-2,2,5,11,14-pentamethyl-4,7,10-trioxo-6-(2-phenylpropan-2-yl)-3-oxa-5,8,11-triazapentadec-13-en-15-oic acid
  参考文献：
  名称：

  Conjugates of ligand linker and cytotoxic agent and related composition and methods of use

  摘要：

  一种包含配体、连接剂和细胞毒性药物的共轭物，其中连接剂为FALA、VLALA、ALAL、ALALA、ChaLALA、ChaChaLAL、NalChaLAL或NalLALA；其组合物；以及以细胞特异性方式传递细胞毒性药物的方法；以及治疗哺乳动物癌症的方法。

  公开号：

  US20050171014A1
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 N-(tert-butoxycarbonyl)-N,β,β-trimethyl-L-phenylalanine-N-[(3S,4E)-6-ethoxy-2,5-dimethyl-6-oxohexa-4-ene-3-yl]-N,3-dimethyl-L-valinamide
  参考文献：
  名称：

  Synthesis and Antimitotic/Cytotoxic Activity of Hemiasterlin Analogues

  摘要：

  The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.

  DOI：

  10.1021/np020375t

文献信息

• Conjugates of ligand linker and cytotoxic agent and related composition and methods of use
  申请人：Tarasova I Nadya

  公开号：US20050171014A1

  公开（公告）日：2005-08-04

  A conjugate comprising a ligand, a linker, and a cytotoxic agent, in which the linker is FALA, VLALA, ALAL, ALALA, ChaLALA, ChaChaLAL, NalChaLAL or NalLALA; a composition thereof; a method of delivering a cytotoxic agent in a cell-specific manner; and a method of treating cancer in a mammal.

  一种包含配体、连接剂和细胞毒性药物的共轭物，其中连接剂为FALA、VLALA、ALAL、ALALA、ChaLALA、ChaChaLAL、NalChaLAL或NalLALA；其组合物；以及以细胞特异性方式传递细胞毒性药物的方法；以及治疗哺乳动物癌症的方法。
• HEMIASTERLIN ANALOGS
  申请人：ANDERSEN Raymond

  公开号：US20090264487A1

  公开（公告）日：2009-10-22

  This invention provides analogs of hemiasterlin, methods of synthesis of the analogs and use of the analogs as a cytotoxic anti-mitotic agents.

  这项发明提供了半星丝菌素的类似物，以及类似物的合成方法和将类似物用作细胞毒性抗有丝分裂剂的用途。
• Hemiasterlin Derivative Having Cysteine Residue
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：US20220144889A1

  公开（公告）日：2022-05-12

  A compound represented by formula (1): wherein b represents an integer of 1 to 5; X represents —NH— or —CO—; Z represents a group represented, for example, by formula (Z-1); R 1 represents a hydrogen atom or (AB) m ; AB represents a particular amino acid residue, and when there is a plurality of ABs, each AB may be the same as or different from each other and ABs are bonded to each other via an amide bond; m represents an integer of 1 to 9; R 2 represents a hydroxy group or (AC) g ; AC represents a particular amino acid residue, and when there is a plurality of ACs, each AC may be the same as or different from each other and ACs are bonded to each other via an amide bond; and g represents an integer of 1 to 9, or a salt thereof.

  化合物的化学式为（1）：其中b表示1至5的整数；X表示—NH—或—CO—；Z表示由化学式（Z-1）表示的基团；R1表示氢原子或(AB)m；AB表示特定的氨基酸残基，当存在多个AB时，每个AB可以相同或不同，并且AB通过酰胺键相互连接；m表示1至9的整数；R2表示羟基或(AC)g；AC表示特定的氨基酸残基，当存在多个AC时，每个AC可以相同或不同，并且AC通过酰胺键相互连接；g表示1至9的整数；或其盐。
• Hemiasterlin Derivative and Antibody-Drug Conjugate Thereof
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：US20220125941A1

  公开（公告）日：2022-04-28

  A compound represented by formula (1): wherein R 1 represents a hydrogen atom or a sulfonyl group; and Z represents a group represented by formula (Z-1), or a salt thereof.

  化合物的化学式为（1）：其中R1代表氢原子或磺酰基；Z代表化学式（Z-1）所代表的基团或其盐。
• Agent for Eliminating Pluripotent Stem Cells
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：US20220202948A1

  公开（公告）日：2022-06-30

  An agent for eliminating a pluripotent stem cell, the agent comprising an antibody-drug conjugate that releases a compound represented by formula (1-1): wherein b represents an integer of 1 to 5; and Z represents a group represented by formula (Z-1) or formula (Z-2), or a salt thereof.

  一种用于消除多能干细胞的药剂，该药剂包括一种抗体-药物结合物，该结合物释放出一种由式（1-1）表示的化合物，其中b表示1至5的整数；Z表示式（Z-1）或式（Z-2）表示的基团，或其盐。