硼替佐米杂质79 | 847644-46-6

• 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
• 中文名称: 硼替佐米杂质79
• 英文名称: 2-amino-N-[(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl]acetamide
• 英文别名: 2-amino-N-{(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}acetamide；2-amino-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]acetamide
• CAS: 847644-46-6
• 化学式: C₁₇H₃₁BN₂O₃
• 分子量: 322.256
• InChiKey: VJVSBWFMAXJSSI-LHLGERLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.74
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硼替佐米杂质79 在 N-甲基吗啉 、 盐酸 、 三异丁基硼酸 、 水 、 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 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(1R)-1-({[(2-bromobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  tert-butyl [2-({(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-2-oxoethyl]carbamate 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 硼替佐米杂质79
  参考文献：
  名称：

  Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors

  摘要：

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.

  DOI：

  10.1021/jm200460q

文献信息

• Proteasome inhibitors
  申请人：Olhava Edward J.

  公开号：US20090042836A1

  公开（公告）日：2009-02-12

  The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种作为蛋白酶体抑制剂有用的新化合物。本发明还提供了包含本发明化合物的制药组合物，以及使用这些组合物治疗各种疾病的方法。
• PROTEASOME INHIBITORS
  申请人：Olhava Edward J.

  公开号：US20100204180A1

  公开（公告）日：2010-08-12

  The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新型化合物，可用作蛋白酶体抑制剂。本发明还提供了包含本发明化合物的药物组合物，并提供了使用这些组合物治疗各种疾病的方法。
• Proteasome Inhibitors
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20150011506A1

  公开（公告）日：2015-01-08

  The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新型化合物，可用作蛋白酶体抑制剂。本发明还提供包含本发明化合物的制药组合物以及使用这些组合物治疗各种疾病的方法。
• ——
  作者：

  DOI：——

  日期：——
• Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors
  作者：Lawrence J. Milo、Jack H. Lai、Wengen Wu、Yuxin Liu、Hlaing Maw、Youhua Li、Zhiping Jin、Ying Shu、Sarah E. Poplawski、Yong Wu、David G. Sanford、James L. Sudmeier、William W. Bachovchin

  DOI：10.1021/jm200460q

  日期：2011.7.14

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.