(E)-(S)-4-{[(S)-2-((S)-3,3-Dimethyl-2-methylamino-butyrylamino)-3,3-dimethyl-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic acid | 228266-42-0

• 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)-2-((S)-3,3-Dimethyl-2-methylamino-butyrylamino)-3,3-dimethyl-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic acid
• 英文别名: L-Valinamide, N,3-dimethyl-L-valyl-N-[(1S,2E)-3-carboxy-1-(1-methylethyl)-2-butenyl]-N,3-dimethyl-；(E,4S)-4-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid
• CAS: 228266-42-0
• 化学式: C₂₂H₄₁N₃O₄
• 分子量: 411.585
• InChiKey: KLORAOGGZZEIGS-JDRICQGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  98.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E)-(S)-4-{[(S)-2-((S)-3,3-Dimethyl-2-methylamino-butyrylamino)-3,3-dimethyl-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic acid ethyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 (E)-(S)-4-{[(S)-2-((S)-3,3-Dimethyl-2-methylamino-butyrylamino)-3,3-dimethyl-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic 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

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。
• VAR2CSA-drug conjugates
  申请人：ZYMEWORKS INC.

  公开号：US10675355B2

  公开（公告）日：2020-06-09

  VAR2CSA-drug conjugates having biological activity are disclosed. Methods associated with preparation and use of such conjugates, as well as pharmaceutical compositions comprising such conjugates, are also disclosed.

  本研究公开了具有生物活性的 VAR2CSA-药物共轭物。还公开了与制备和使用此类共轭物相关的方法，以及包含此类共轭物的药物组合物。
• Hemiasterlin derivatives and uses thereof in the treatment of cancer
  申请人：Kowalczyk J. James

  公开号：US20080051434A1

  公开（公告）日：2008-02-28

  The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.
• Hemiasterlin Derivatives and Uses Thereof
  申请人：Campagna Silvio A.

  公开号：US20080108820A1

  公开（公告）日：2008-05-08

  The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.
• HEMIASTERLIN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF CANCER
  申请人：KOWALCZYK James J.

  公开号：US20100063095A1

  公开（公告）日：2010-03-11

  The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.