(E)-(S)-4-[((R)-2-tert-Butoxycarbonylamino-3-methyl-3-methylsulfanyl-butyryl)-methyl-amino]-2,5-dimethyl-hex-2-enoic acid ethyl ester | 676628-88-9

• 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: (E)-(S)-4-[((R)-2-tert-Butoxycarbonylamino-3-methyl-3-methylsulfanyl-butyryl)-methyl-amino]-2,5-dimethyl-hex-2-enoic acid ethyl ester
• 英文别名: Ethyl (2E,4S)-4-[[N-(tert-butoxycarbonyl)-3-(methylsulfanyl)-L-valyl](methyl)amino]-2,5-dimethyl-2-hexenoate；ethyl (E,4S)-2,5-dimethyl-4-[methyl-[(2R)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-methylsulfanylbutanoyl]amino]hex-2-enoate
• CAS: 676628-88-9
• 化学式: C₂₂H₄₀N₂O₅S
• 分子量: 444.636
• InChiKey: HHKYQVDPPBZHAY-IDGBWPAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-(S)-4-[((R)-2-tert-Butoxycarbonylamino-3-methyl-3-methylsulfanyl-butyryl)-methyl-amino]-2,5-dimethyl-hex-2-enoic acid ethyl ester 在 盐酸 、 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成 (E)-(S)-4-({(R)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-3-(4-methoxy-phenyl)-3-methyl-butyrylamino]-3-methyl-3-methylsulfanyl-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid
  参考文献：
  名称：

  Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents

  摘要：

  Modifications of the B-segment of HTI-286 (2) produced a class of analogs incorporating heteroatom-substituents. The structure-activity relationship was studied. Analogs bearing methylsulfide and fluoride groups exhibited potency comparable to that of the parent compound HTI-286 and to paclitaxel in cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines. Several analogs showed strong inhibition of tubulin polymerization. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.077
• 作为产物：
  描述：

  L-缬氨酸,3-(甲硫基)- 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-(S)-4-[((R)-2-tert-Butoxycarbonylamino-3-methyl-3-methylsulfanyl-butyryl)-methyl-amino]-2,5-dimethyl-hex-2-enoic acid ethyl ester
  参考文献：
  名称：

  Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents

  摘要：

  Modifications of the B-segment of HTI-286 (2) produced a class of analogs incorporating heteroatom-substituents. The structure-activity relationship was studied. Analogs bearing methylsulfide and fluoride groups exhibited potency comparable to that of the parent compound HTI-286 and to paclitaxel in cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines. Several analogs showed strong inhibition of tubulin polymerization. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.077

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。
• Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents
  作者：Chuan Niu、Daniel Smith、Arie Zask、Frank Loganzo、Carolyn Discafani、Carl Beyer、Lee Greenberger、Semiramis Ayral-Kaloustian

  DOI：10.1016/j.bmcl.2004.05.077

  日期：2004.8

  Modifications of the B-segment of HTI-286 (2) produced a class of analogs incorporating heteroatom-substituents. The structure-activity relationship was studied. Analogs bearing methylsulfide and fluoride groups exhibited potency comparable to that of the parent compound HTI-286 and to paclitaxel in cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines. Several analogs showed strong inhibition of tubulin polymerization. (C) 2004 Elsevier Ltd. All rights reserved.