benzyl (S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate | 935888-15-6

• 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)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate
• 英文别名: benzyl ((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)carbamate；benzyl N-[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 935888-15-6
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: YVLADUHOLDAJKT-FXAWDEMLSA-N

物化性质

• 沸点：
  519.9±50.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate 在 palladium on carbon 、 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， -5.0 ℃ 、354.66 kPa 条件下， 反应 7.0h， 生成 US10640533, Identification number CX13-605
  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：

  苄基(S)-1-(N-甲氧基-N-甲基氨基甲酰基)-2-苯乙基氨基甲酸酯 在 叔丁基过氧化氢 、 sodium tetrahydroborate 、 bis(acetylacetonate)oxovanadium 、 cerium(III) chloride heptahydrate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 癸烷 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 benzyl (S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate
  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

文献信息

• Compounds for enzyme inhibition
  申请人：Zhou Han-Jie

  公开号：US20070105786A1

  公开（公告）日：2007-05-10

  Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles

  基于肽的化合物，包括含杂原子的三元环，能够高效且选择性地抑制与蛋白酶体相关的N-末端亲核（Ntn）水解酶的特定活性。这些基于肽的化合物包括环氧化物或氮杂环丙烷，并在N-末端进行官能化。除了其他治疗用途外，预计这些基于肽的化合物将显示抗炎性能和抑制细胞增殖。由于它们的生物利用度特性，这些基于肽的蛋白酶体抑制剂可以通过口服给药进行。
• 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：
• 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：
• Compounds For Enzyme Inhibition
  申请人：Onyx Therapeutics, Inc.

  公开号：EP2623113A2

  公开（公告）日：2013-08-07

  Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

  肽基化合物包括含杂原子的三元环，能有效并选择性地抑制与蛋白酶体相关的 N-末端亲核（Ntn）水解酶的特定活性。肽基化合物包括环氧化物或氮丙啶，并在 N 端进行了官能化。除其他治疗作用外，肽基化合物还具有抗炎和抑制细胞增殖的作用。由于这些肽基蛋白酶体抑制剂具有生物利用度高的特点，因此可以口服给药。
• 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.