(S)-methyl 2-(3-((S)-1-(((5S,8S,E)-5-isopropyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl)amino)-1-oxo-3-phenylpropan-2-yl)ureido)-3-methylbutanoate

• 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: (S)-methyl 2-(3-((S)-1-(((5S,8S,E)-5-isopropyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl)amino)-1-oxo-3-phenylpropan-2-yl)ureido)-3-methylbutanoate
• 英文别名: methyl (2S)-2-[[(2S)-1-[[(3E,5S,8S)-2,7-dioxo-5-propan-2-yl-1,6-diazacyclododec-3-en-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoylamino]-3-methylbutanoate
• 化学式: C₂₉H₄₃N₅O₆
• 分子量: 557.69
• InChiKey: HJMHHSCOKJPSPN-OMZSPBFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  L-苯基丙氨酸叔丁酯 在 甲酸 、 水 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.33h， 生成 (S)-methyl 2-(3-((S)-1-(((5S,8S,E)-5-isopropyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl)amino)-1-oxo-3-phenylpropan-2-yl)ureido)-3-methylbutanoate
  参考文献：
  名称：

  Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines

  摘要：

  Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.041

文献信息

• [EN] NOVEL SYRINGOLIN ANALOGUES AND METHODS OF MAKING AND USING SAME<br/>[FR] NOUVEAUX ANALOGUES DE SYRINGOLINE ET PROCÉDÉS DE FABRICATION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV BROWN

  公开号：WO2016182968A1

  公开（公告）日：2016-11-17

  The present invention provides, in certain aspects, novel syringolin analogues, In certain embodiments, the compounds of the invention are proteasome inhibitors, In other embodiments, the compounds treat or prevent a cancer such as, but not limited to, leukemia in a subject,

  本发明在某些方面提供了新颖的西林类似物。在某些实施方式中，本发明的化合物是蛋白酶体抑制剂。在其他实施方式中，这些化合物用于治疗或预防主体中的癌症，如但不限于白血病。
• Syringolin analogues and methods of making and using same
  申请人：BROWN UNIVERSITY

  公开号：US10597368B2

  公开（公告）日：2020-03-24

  The present invention provides, in certain aspects, novel syringolin analogues, In certain embodiments, the compounds of the invention are proteasome inhibitors, In other embodiments, the compounds treat or prevent a cancer such as, but not limited to, leukemia in a subject.

  在某些实施方案中，本发明的化合物是蛋白酶体抑制剂；在其他实施方案中，本发明的化合物可以治疗或预防受试者的癌症，例如但不限于白血病。
• NOVEL SYRINGOLIN ANALOGUES AND METHODS OF MAKING AND USING SAME
  申请人：BROWN UNIVERSITY

  公开号：US20200216401A1

  公开（公告）日：2020-07-09

  The present invention provides, in certain aspects, novel syringolin analogues, In certain embodiments, the compounds of the invention are proteasome inhibitors, In other embodiments, the compounds treat or prevent a cancer such as, but not limited to, leukemia in a subject,
• Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines
  作者：Kyle A. Totaro、Dominik Barthelme、Peter T. Simpson、Robert T. Sauer、Jason K. Sello

  DOI：10.1016/j.bmc.2015.07.041

  日期：2015.9

  Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs. (c) 2015 Elsevier Ltd. All rights reserved.