4-bromo-N-β,β-trimethylphenylalanyl-N¹-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N¹,3-dimethyl-valinamide | 676627-57-9

• 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: 4-bromo-N-β,β-trimethylphenylalanyl-N¹-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N¹,3-dimethyl-valinamide
• 英文别名: ethyl (E,4S)-4-[[(2S)-2-[[3-(4-bromophenyl)-3-methyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoate
• CAS: 676627-57-9
• 化学式: C₂₉H₄₆BrN₃O₄
• 分子量: 580.606
• InChiKey: NPKHQQRAPCRMIM-DEYDNGSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  4-bromo-N-β,β-trimethylphenylalanyl-N¹-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N¹,3-dimethyl-valinamide 在 lithium hydroxide 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-β,β-trimethyl-4-[(E)-2-phenylvinyl]-L-phenylalanyl-N¹-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N¹,3-dimethyl-L-valinamide
  参考文献：
  名称：

  Probing the Interaction of HTI-286 with Tubulin Using a Stilbene Analogue

  摘要：

  HTI-286 is a synthetic analogue of the natural product hemiasterlin. HTI-286 is a potent antitumor agent that induces tubulin oligomerization. To investigate the binding stoichiometry and the binding site during this ligand-induced tubulin association, we synthesized an analogue of HTI-286 containing the chromophore stilbene. Using the distinct absorbance of the stilbene analogue, we determined the amounts of inhibitors bound to different tubulin oligomers by analytical ultracentrifugation. Herein we describe our findings based on these experiments. At the ratio of inhibitor to protein equal to or greater than 1, the stilbene analogue induces oligomerization of tubulin to a ring structure. The binding stoichiometry in the ring is one inhibitor per tubulin monomer (defined as an alpha/beta-heterodimer). At the ratio of inhibitor to protein less than 1, tubulin forms multiple intermediates, with the binding stoichiometry less than one inhibitor per tubulin monomer for all intermediates. The stable complex between the inhibitor and tubulin monomer was not detected under our experimental conditions. The binding site of the stilbene analogue does not overlap with the classic tubulin-binding agent, colchicine.

  DOI：

  10.1021/ja048619e
• 作为产物：
  描述：

  3-methyl-3-(4-bromophenyl)-2-oxobutanoic 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 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 4-bromo-N-β,β-trimethylphenylalanyl-N¹-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N¹,3-dimethyl-valinamide
  参考文献：
  名称：

  Probing the Interaction of HTI-286 with Tubulin Using a Stilbene Analogue

  摘要：

  HTI-286 is a synthetic analogue of the natural product hemiasterlin. HTI-286 is a potent antitumor agent that induces tubulin oligomerization. To investigate the binding stoichiometry and the binding site during this ligand-induced tubulin association, we synthesized an analogue of HTI-286 containing the chromophore stilbene. Using the distinct absorbance of the stilbene analogue, we determined the amounts of inhibitors bound to different tubulin oligomers by analytical ultracentrifugation. Herein we describe our findings based on these experiments. At the ratio of inhibitor to protein equal to or greater than 1, the stilbene analogue induces oligomerization of tubulin to a ring structure. The binding stoichiometry in the ring is one inhibitor per tubulin monomer (defined as an alpha/beta-heterodimer). At the ratio of inhibitor to protein less than 1, tubulin forms multiple intermediates, with the binding stoichiometry less than one inhibitor per tubulin monomer for all intermediates. The stable complex between the inhibitor and tubulin monomer was not detected under our experimental conditions. The binding site of the stilbene analogue does not overlap with the classic tubulin-binding agent, colchicine.

  DOI：

  10.1021/ja048619e

文献信息

• Method of treating resistant tumors
  申请人：Wyeth Holdings Corporation

  公开号：US20040121965A1

  公开（公告）日：2004-06-24

  The invention provides a method of treating or inhibiting the growth of or eradicating a tumor in a mammal in need thereof wherein said tumor is resistant to at least one chemotherapeutic agent which method comprises providing to said mammal an effective amount of a compound of Formula II or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制哺乳动物体内对至少一种化疗药物产生耐药性的肿瘤生长或根除肿瘤的方法，该方法包括向该哺乳动物提供有效量的公式II化合物或其药学上可接受的盐。
• [EN] METHOD OF TREATING RESISTANT TUMORS<br/>[FR] METHODE DE TRAITEMENT DE TUMEURS RESISTANTES
  申请人：WYETH CORP

  公开号：WO2004026293A2

  公开（公告）日：2004-04-01

  The invention provides a method of treating or inhibiting the growth of or eradicating a tumor in a mammal in need thereof wherein said tumor is resistant to at least one chemotherapeutic agents which method comprises providing to said mammal an effective amount of a compound of Formula II or a pharmaceutically acceptable salt thereof.