{(S)-3-methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylaminoformyl]-butyl}-carbamic acid tert-butyl ester | 477254-83-4

• 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)-3-methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylaminoformyl]-butyl}-carbamic acid tert-butyl ester
• 英文别名: {(S)-3-Methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-butyl}-carbamic acid tert-butyl ester；{(S)-3-Methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)butylcarbamoyl]-butyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-4-methyl-1-[[(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]amino]-1-oxopentan-2-yl]carbamate
• CAS: 477254-83-4
• 化学式: C₂₆H₄₇BN₂O₅
• 分子量: 478.481
• InChiKey: BHEXYRLEJPYYAS-BEIHLXIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {(S)-3-methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylaminoformyl]-butyl}-carbamic acid tert-butyl ester 、 (S)-2-(Biphenyl-3-ylamino)-3-(3,4-dimethoxyphenyl)-propionic acid 生成 (S)-2-[(S)-2-(Biphenyl-3-ylamino)-3-(3,4-dimethoxy-phenyl)-propionylamino]-4-methyl-pentanoic acid [(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butyl]-amide
  参考文献：
  名称：

  2-{N-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl}-amino}-alkylboronic acid derivatives

  摘要：

  本发明涉及2-{[N-（2-氨基-3-（杂环芳基或芳基）丙酰基）-氨基酰基]-氨基}-烷基硼酸盐衍生物，制备这种化合物的方法，制药制剂，以及在制备治疗温血动物（包括人类）的药物组合物中使用这种衍生物的用途。

  公开号：

  US06933290B2
• 作为产物：
  描述：

  BOC-L-亮氨酸 、 (R)-boroLeu-(+)-pinanediol 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 {(S)-3-methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylaminoformyl]-butyl}-carbamic acid tert-butyl ester
  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

• Methods and compositions for inducing apoptosis in cancer cells
  申请人：Nasoff Marc

  公开号：US20050079172A1

  公开（公告）日：2005-04-14

  Anti-DR4 or Anti-DR5 antibody agonists, combined with apoptosis-inducing agents, synergistically induce apoptosis in cancer cells.

  Anti-DR4或Anti-DR5抗体激动剂，与诱导细胞凋亡的药物结合使用，能够协同诱导癌细胞的凋亡。
• 2-{[N-(2-amino-3-(heteroaryl or aryl) propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives
  申请人：Furet Pascal

  公开号：US20050239716A1

  公开（公告）日：2005-10-27

  The present invention relates to compounds of formula I wherein the substituents are as defined in the description, to processes for the preparation thereof, to pharmaceutical preparations comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  本发明涉及式I的化合物，其中取代基如描述中所定义，以及其制备方法，包括这些化合物的制药制剂，以及在制备治疗温血动物，包括人类的药物组合物时的使用。
• 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl}-amino}-alkylboronic acid derivatives
  申请人：——

  公开号：US20040167337A1

  公开（公告）日：2004-08-26

  The present invention relates to compounds of formula (I) their synthesis and pharmaceutical compositions thereof for the therapeutic treatment of a proliferative diseases in warm-blooded animals, including humans. 1

  本发明涉及式（I）化合物，它们的合成以及制备用于治疗温血动物，包括人类的增殖性疾病的制药组合物。
• Methods and compositions for inducing apoptosis in cancer cells with an anti-DR5 antibody
  申请人：IRM LLC

  公开号：US08173128B2

  公开（公告）日：2012-05-08

  Anti-DR5 antibody agonists, combined with apoptosis-inducing agents, synergistically induce apoptosis in cancer cells.

  Anti-DR5抗体激动剂与诱导细胞凋亡的药物联合使用，能够协同诱导癌细胞凋亡。