(E)-(S)-4-({(S)-3,3-Dimethyl-2-[(S)-3-methyl-2-methylamino-3-(3-vinyl-phenyl)-butyrylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester | 676627-50-2

• 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-({(S)-3,3-Dimethyl-2-[(S)-3-methyl-2-methylamino-3-(3-vinyl-phenyl)-butyrylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester
• 英文别名: N,beta,beta-Trimethyl-3-vinyl-L-phenylalanyl-N1-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N1,3-dimethyl-L-valinamide；ethyl (E,4S)-4-[[(2S)-2-[[(2S)-3-(3-ethenylphenyl)-3-methyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoate
• CAS: 676627-50-2
• 化学式: C₃₁H₄₉N₃O₄
• 分子量: 527.748
• InChiKey: DZGXOHJJODAPRR-ZYIWTSOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 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：

  (E)-(S)-4-({(S)-3,3-Dimethyl-2-[(S)-3-methyl-2-methylamino-3-(3-vinyl-phenyl)-butyrylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester 在 palladium on activated charcoal lithium hydroxide 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 (E)-(S)-4-({(S)-2-[(S)-3-(3-Ethyl-phenyl)-3-methyl-2-methylamino-butyrylamino]-3,3-dimethyl-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid
  参考文献：
  名称：

  Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment

  摘要：

  Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.024
• 作为产物：
  描述：

  、 (E)-(S)-4-({(S)-2-[3-(3-Bromo-phenyl)-3-methyl-2-methylamino-butyrylamino]-3,3-dimethyl-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester 在 四(三苯基膦)钯 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 (E)-(S)-4-({(S)-3,3-Dimethyl-2-[(S)-3-methyl-2-methylamino-3-(3-vinyl-phenyl)-butyrylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester 、 (E)-(S)-4-({(S)-3,3-Dimethyl-2-[(R)-3-methyl-2-methylamino-3-(3-vinyl-phenyl)-butyrylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester
  参考文献：
  名称：

  Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment

  摘要：

  Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.024

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.