{(S)-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane-4-yl)-butylaminoformyl]-ethyl}-carbamic acid tert-butyl ester | 477254-84-5

• 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)-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane-4-yl)-butylaminoformyl]-ethyl}-carbamic acid tert-butyl ester
• 英文别名: {(S)-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]-ethyl}-carbamic acid tert-butyl ester；{(S)-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]-ethyl}-carbamic acid tert-butyl ester；{(S)-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]-ethyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-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-oxopropan-2-yl]carbamate
• CAS: 477254-84-5
• 化学式: C₂₃H₄₁BN₂O₅
• 分子量: 436.4
• InChiKey: IAVUDZXYAMCYKK-BNJDFNGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 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)-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane-4-yl)-butylaminoformyl]-ethyl}-carbamic acid tert-butyl ester 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 (S)-1-acetyl-N-((S)-1-(((R)-3-methyl-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]-dioxaborol-2-yl)butyl)amino)-1-oxopropan-2-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  恶性疟原虫蛋白酶体的新型硼酸盐抑制剂的目标验证和鉴定。

  摘要：

  疟原虫蛋白酶体代表具有针对多个生命周期阶段的活性的化合物的潜在抗疟疾药物靶标。我们筛选了人类蛋白酶体抑制剂（肽基硼酸）文库，并比较了其对纯化的恶性疟原虫和人类20S蛋白酶体的活性。我们选择了四个能有效抑制寄生虫生长并显示出与人类细胞系相比可抑制恶性疟原虫生长的选择性的命中物。选择恶性疟原虫对临床使用的蛋白酶体抑制剂硼替佐米具有体外抗性，并应用全基因组测序来鉴定蛋白酶体β5亚基中的突变。活性位点分析揭示了抑制剂功能，可以保留针对硼替佐米耐药株的有效活性。底物分析显示P. 恶性疟原虫20S蛋白酶体活性位点的偏好，将有助于尝试设计更多选择性抑制剂。这项工作为鉴定选择性靶向恶性疟原虫蛋白酶体的抗疟药物前导提供了起点。

  DOI：

  10.1021/acs.jmedchem.8b01161
• 作为产物：
  描述：

  {(S)-2-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-]propyl}-carbamic acid tert-butyl ester 、 N-叔丁氧羰基-L-丙氨酸 生成 {(S)-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane-4-yl)-butylaminoformyl]-ethyl}-carbamic acid tert-butyl ester
  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

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。
• 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.