tert-butyl (S)-3-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-5-bromo-4-oxopentanoate | 294860-44-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: tert-butyl (S)-3-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-5-bromo-4-oxopentanoate
• 英文别名: tert-butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-bromo-4-oxopentanoate；t-Butyl (3S)-5-bromo-3-[(9H-9-fluorenylmethoxy)carbonyl]amino-4-oxo-pentanoate；tert-butyl (3S)-5-bromo-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxopentanoate
• CAS: 294860-44-9
• 化学式: C₂₄H₂₆BrNO₅
• 分子量: 488.378
• InChiKey: TXRNIQPMCKXMSO-FQEVSTJZSA-N

物化性质

• 沸点：
  628.3±55.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-3-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-5-bromo-4-oxopentanoate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 t-Butyl (3S)-5-azido-3-[(9H-9-fluorenylmethoxy)carbonyl]amino-4-oxo-pentanoate
  参考文献：
  名称：

  Gamma-ketoacid dipeptide derivatives as inhibitors of caspase-3

  摘要：

  该发明涵盖了公式I的新化合物，这些化合物在治疗caspase-3介导的疾病中很有用。该发明还涵盖了包含公式I化合物的某些药物组合物，以及治疗caspase-3介导的疾病的方法。

  公开号：

  US20030045478A1
• 作为产物：
  描述：

  Fmoc-Asp(OBu^t)-DAM 在 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.25h， 生成 tert-butyl (S)-3-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-5-bromo-4-oxopentanoate
  参考文献：
  名称：

  合成不依赖序列的肽基-氟甲基酮的通用固相方法†

  摘要：

  我们在这里提出了一种新的，通用的，固相策略，用于使用标准的Fmoc肽化学方法合成与序列无关的肽基-氟甲基酮。我们的方法是基于双功能接头的合成，其允许在肽序列的C-末端掺入氨基酸氟甲基酮单元。还描述了该方法在针对SENP的基于活性的探针的合成中的应用。

  DOI：

  10.1039/c2ob25096a

文献信息

• Gamma-ketoacid dipeptides as inhibitors of caspase-3
  申请人：Merk Frosst Canada & Co.

  公开号：US06225288B1

  公开（公告）日：2001-05-01

  Compounds represented by formula I: as well as pharmaceutically acceptable salts, esters and hydrates thereof are disclosed along with pharmaceutical compositions and methods of treatment. The compounds are useful as inhibitors of caspase-3, which is implicated in modulating apoptosis.

  由式I表示的化合物，以及其药学上可接受的盐、酯和水合物，以及配制的药物组合物和治疗方法被揭示。这些化合物可用作caspase-3的抑制剂，该酶参与调节细胞凋亡。
• Pyrazinones, compositions containing such compounds and methods of use
  申请人：Merck Frosst Canada & Co.

  公开号：US06444811B1

  公开（公告）日：2002-09-03

  Compounds represented by formula I: as well as pharmaceutically acceptable salts, esters, N-oxides and hydrates thereof are disclosed. Pharmaceutical compositions and methods of use are also included. The compounds are active against the caspase-3 enzyme, and thus are useful to treat fin caspase-3 mediated diseases and conditions.

  公式I代表的化合物以及其药用盐、酯、N-氧化物和水合物已被披露。药物组合物和使用方法也包括在内。这些化合物对caspase-3酶具有活性，因此可用于治疗与fin caspase-3介导的疾病和症状。
• An improved method for the incorporation of fluoromethyl ketones into solid phase peptide synthesis techniques
  作者：Dhira Joshi、Jennifer C. Milligan、Theresa U. Zeisner、Nicola O'Reilly、John F. X. Diffley、George Papageorgiou

  DOI：10.1039/d1ra03046a

  日期：——

  An improved and expedient technique for the synthesis of peptidyl-fluoromethyl ketones is described. The methodology is based on prior coupling of an aspartate fluoromethyl ketone to a linker and mounting it onto resin-bound methylbenzhydrylamine hydrochloride. Subsequently, by utilising standard Fmoc peptide procedures, a number of short Z-protected peptides were synthesised and assessed as possible

  描述了一种改进且方便的肽基氟甲基酮合成技术。该方法基于天冬氨酸氟甲基酮与连接体的预先偶联，并将其安装到树脂结合的甲基二苯甲基胺盐酸盐上。随后，通过利用标准 Fmoc 肽程序，合成了许多短 Z 保护肽，并评估它们是否可能是 SARS-CoV-2 (3CL pro ) 主要蛋白酶的抑制剂。
• Lipophilic versus hydrogen-bonding effect in P3 on potency and selectivity of valine aspartyl ketones as caspase 3 inhibitors
  作者：Christophe Mellon、Reneé Aspiotis、Cameron W. Black、Christopher I. Bayly、Erich L. Grimm、André Giroux、Yongxin Han、Elise Isabel、Daniel J. McKay、Donald W. Nicholson、Dita M. Rasper、Sophie Roy、John Tam、Nancy A. Thornberry、John P. Vaillancourt、Steven Xanthoudakis、Robert Zamboni

  DOI：10.1016/j.bmcl.2005.05.116

  日期：2005.9

  Caspase 3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact in the treatment of several degenerative diseases. The P, aspartic acid residue is a required element of recognition for this enzyme that was maintained constant along with the adjacent natural valine as the P-2 group. The thiobenzylmethylketone warhead on the aspartate was conveniently handled through solid-phase synthesis allowing modification in the P-3 region that eventually led to simpler derivatives with increased potency against caspase 3. The key to such an effect is the introduction of hydroxyl group alpha to the P3 carbonyl. (c) 2005 Elsevier Ltd. All rights reserved.
• Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design
  作者：Ingrid C. Choong、Willard Lew、Dennis Lee、Phuongly Pham、Matthew T. Burdett、Joni W. Lam、Christian Wiesmann、Tinh N. Luong、Bruce Fahr、Warren L. DeLano、Robert S. McDowell、Darin A. Allen、Daniel A. Erlanson、Eric M. Gordon、Tom O'Brien

  DOI：10.1021/jm020230j

  日期：2002.11.1

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.