benzyl (S)-4-methyl-3-oxo-1-phenylpent-4-en-2-ylcarbamate | 960374-25-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (S)-4-methyl-3-oxo-1-phenylpent-4-en-2-ylcarbamate
• 英文别名: (S)-benzyl (4-methyl-3-oxo-1-phenylpent-4-en-2-yl)carbamate；benzyl N-[(2S)-4-methyl-3-oxo-1-phenylpent-4-en-2-yl]carbamate
• CAS: 960374-25-8
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: REUUSACAXHHFKN-SFHVURJKSA-N

物化性质

• 沸点：
  506.4±50.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl (S)-4-methyl-3-oxo-1-phenylpent-4-en-2-ylcarbamate 在 叔丁基过氧化氢 、 sodium tetrahydroborate 、 bis(acetylacetonate)oxovanadium 、 cerium(III) chloride heptahydrate 作用下， 以 四氢呋喃 、 甲醇 、 癸烷 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 benzyl N-[(2S)-1-hydroxy-1-[(2R)-2-methyloxiran-2-yl]-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  [EN] EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION
  [FR] COMPOSÉS D'ÉPOXYCÉTONE POUR L'INHIBITION D'ENZYMES

  摘要：

  公开号：

  WO2016011088A3
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 在 聚合甲醛 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.25h， 生成 benzyl (S)-4-methyl-3-oxo-1-phenylpent-4-en-2-ylcarbamate
  参考文献：
  名称：

  一种制备异丙烯酮化合物的方法

  摘要：

  本发明公开了一种制备异丙烯酮化合物的方法，包括1)将式IV化合物与乙基膦酸酯溶于有机溶剂中，加入乙基膦酸酯活化剂，反应完全后，用淬灭剂终止反应，制得化合物V；2)将式V化合物与甲醛在溶剂中，在碱的存在下发生缩合反应，制得异丙烯酮化合物。该方法简便、高效、成本低廉，适用于工业化生产。

  公开号：

  CN106316887A

文献信息

• Compounds for enzyme inhibition
  申请人：Shenk D. Kevin

  公开号：US20070293465A1

  公开（公告）日：2007-12-20

  One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

  该发明的一个方面涉及优先抑制免疫蛋白酶体活性而非构成性蛋白酶体活性的抑制剂。在某些实施例中，该发明涉及治疗免疫相关疾病，包括给予该发明的化合物。在某些实施例中，该发明涉及治疗癌症，包括给予该发明的化合物。
• FLUORINATED EPOXYKETONE-BASED TETRAPEPTIDE COMPOUNDS AND USES THEREOF AS PROTEASOME INHIBITORS
  申请人：FLUORINOV PHARMA INC.

  公开号：US20150218212A1

  公开（公告）日：2015-08-06

  The present application relates to novel fluorinated epoxyketone-based tetrapeptide compounds, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions mediated by proteasome inhibition. In particular, the present application includes compounds of Formula I, and compositions and uses thereof:

  本申请涉及一种新颖的含氟环氧酮基四肽化合物，包含这些化合物的组合物及其用途，特别是用于治疗由蛋白酶体抑制介导的疾病、紊乱或状况。特别是，本申请包括公式I的化合物，以及其组合物和用途：
• Crystalline tripeptide epoxy ketone protease inhibitors
  申请人：Onyx Therapeutics, Inc.

  公开号：US09403868B2

  公开（公告）日：2016-08-02

  The invention relates to crystalline tripeptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions.

  本发明涉及晶体三肽酮环氧化合物、其制备方法及相关药物组合物。
• FLUORINATED EPOXYKETONE-BASED COMPOUNDS AND USES THEREOF AS PROTEASOME INHIBITORS
  申请人：FLUORINOV PHARMA INC.

  公开号：US20150203534A1

  公开（公告）日：2015-07-23

  The present application relates to novel fluorinated epoxyketone-based compounds, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions mediated by proteasome inhibition, in particular, the present application includes compounds of Formula I, and compositions and uses thereof:

  本申请涉及新型氟代环氧酮基化合物，包括这些化合物的组合物和它们的用途，特别是用于治疗由蛋白酶体抑制介导的疾病、紊乱或病况，特别是本申请包括公式I的化合物，以及它们的组合物和用途：
• Design and Synthesis of an Orally Bioavailable and Selective Peptide Epoxyketone Proteasome Inhibitor (PR-047)
  作者：Han-Jie Zhou、Monette A. Aujay、Mark K. Bennett、Maya Dajee、Susan D. Demo、Ying Fang、Mark N. Ho、Jing Jiang、Christopher J. Kirk、Guy J. Laidig、Evan R. Lewis、Yan Lu、Tony Muchamuel、Francesco Parlati、Eileen Ring、Kevin D. Shenk、Jamie Shields、Peter J. Shwonek、Timothy Stanton、Congcong M. Sun、Catherine Sylvain、Tina M. Woo、Jinfu Yang

  DOI：10.1021/jm801329v

  日期：2009.5.14

  Proteasome inhibition has been validated as a therapeutic modality in the treatment of multiple myeloma and Non-Hodgkin's lymphoma. Carfilzomib, an epoxyketone currently undergoing clinical trials in malignant: diseases, is a highly selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome: A chemistry effort was initiated to discover orally bioavailable analogues of carfilzomib, which would have potential for improved dosing flexibility and patient convenience over, intravenously administered agents. The lead. compound, 2-Me-5-thiazole-Ser(OMe)-Ser(OMe)-Phe-ketoepoxide (58) (PR-047), selectively inhibited CT-L activity of both the constitutive proteasome (beta 5) and immunoproteasome (LMP7) and demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It was well tolerated with repeated oral. administration at doses resulting in > 80% proteasome inhibition in most tissues and elicited an antitumor response equivalent to intravenously administered carfilzomib in multiple human tumor xenograft and mouse syngeneic models. The favorable pharmacologic profile supports its further development for the treatment of malignant diseases.