N,beta,beta,3,4-pentamethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N1,3-dimethyl-L-valinamide | 676631-97-3

• 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: N,beta,beta,3,4-pentamethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N1,3-dimethyl-L-valinamide
• 英文别名: (E,4S)-4-[[(2S)-2-[[(2S)-3-(3,4-dimethylphenyl)-3-methyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid
• CAS: 676631-97-3
• 化学式: C₂₉H₄₇N₃O₄
• 分子量: 501.71
• InChiKey: GEGQLUKUTCSFHJ-SOLWDGIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  98.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,beta,beta,3,4-pentamethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N1,3-dimethyl-L-valinamide 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-1-[(E,4S)-4-[[(2S)-2-[[(2S)-3-(3,4-dimethylphenyl)-3-methyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors

  摘要：

  Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein. Amides derived from proline had potency comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols or its conversion to acidic heterocycles also gave potent analogs. Synthetic modifications of the carboxylic acid could be carried out selectively using a wide range of synthetic reagents. Proline analog 3 was found to be effective in a human xenograft model in athymic mice. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.005
• 作为产物：
  描述：

  3-(3,4-dimethyl-phenyl)-3-methyl-2-oxo-butyric acid 在 N-甲基吗啉 、 lithium hydroxide 、 吡啶硼烷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N,beta,beta,3,4-pentamethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N1,3-dimethyl-L-valinamide
  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

• 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。
• 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。
• COMPOUNDS FOR TREATING TUMORS
  申请人：Zask Arie

  公开号：US20080221181A1

  公开（公告）日：2008-09-11

  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.

  本发明提供公式（I）的化合物：其中E，A，B'，R6，R7，R8和R9在说明书中定义，这些化合物表现出抗癌活性并可用于治疗癌症。
• US7390910B2
  申请人：——

  公开号：US7390910B2

  公开（公告）日：2008-06-24
• US7626023B2
  申请人：——

  公开号：US7626023B2

  公开（公告）日：2009-12-01