ethyl (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[2-(methylamino)-2-(1-phenylcyclohexyl)acetyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoate | 676628-50-5

• 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: ethyl (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[2-(methylamino)-2-(1-phenylcyclohexyl)acetyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoate
• CAS: 676628-50-5
• 化学式: C₃₂H₅₁N₃O₄
• 分子量: 541.775
• InChiKey: CUDGUNMUXKSKDP-KRAHIKKBSA-N

物化性质

• 沸点：
  672.5±55.0 °C(Predicted)
• 密度：
  1.043±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.66
• 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 (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[2-(methylamino)-2-(1-phenylcyclohexyl)acetyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)-2-(1-phenylcyclohexyl)acetyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid 、 (2E,4R)-2,5-dimethyl-4-(methyl{3-methyl-N-[(methylamino)(1-phenylcyclohexyl)acetyl]-L-valyl}amino)-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：

  1-Phenylcyclohexanglyoxylsaeure 在 吡啶硼烷 、 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， 生成 ethyl (E,4S)-4-[[(2S)-3,3-dimethyl-2-[[2-(methylamino)-2-(1-phenylcyclohexyl)acetyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoate
  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