ethyl (2E,4S)-4-[{N-[(2S)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate | 845293-09-6

• 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: ethyl (2E,4S)-4-[{N-[(2S)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate
• 英文别名: ethyl (E,4S)-4-[[(2S)-2-[[(2S)-2-(1-adamantyl)-2-(methylamino)acetyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoate
• CAS: 845293-09-6
• 化学式: C₃₀H₅₁N₃O₄
• 分子量: 517.753
• InChiKey: GYROYUBJOUAEBL-XXAKMQJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (2E,4S)-4-[{N-[(2S)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 (2E,4S)-4-[{N-[(2S)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,β,β-Trimethyl-l-phenylalanyl-N-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N¹,3-dimethyl-l-valinamide (HTI-286)

  摘要：

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).

  DOI：

  10.1021/jm040056u
• 作为产物：
  描述：

  adamantan-1-yliodoacetic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 ethyl (2E,4S)-4-[{N-[(2S)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate
  参考文献：
  名称：

  Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,β,β-Trimethyl-l-phenylalanyl-N-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N¹,3-dimethyl-l-valinamide (HTI-286)

  摘要：

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).

  DOI：

  10.1021/jm040056u

文献信息

• Compounds for treating tumors
  申请人：Zask Arie

  公开号：US20050037977A1

  公开（公告）日：2005-02-17

  The invention provides compounds of formula (I): wherein E, A, B′, R 6 , R 7 , R 8 , and R 9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

  该发明提供了以下式（I）的化合物： 其中E、A、B′、R6、R7、R8和R9在规范中定义，这些化合物表现出抗癌活性，并可用于治疗癌症。