3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-7-phenyl-heptanoic acid tert-butyl ester | 273216-01-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-7-phenyl-heptanoic acid tert-butyl ester
• 英文别名: tert-butyl (3S)-3-[(9H)-(9-fluorenyl)methoxycarbonyl]amino-4-oxo-7-phenylheptanoate；tert-Butyl (3S)-3-[(9H-9-fluorenylmethoxy)carbonyl]amino-4-oxo-7-phenylheptanoate；tert-butyl (3S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-7-phenylheptanoate
• CAS: 273216-01-6
• 化学式: C₃₂H₃₅NO₅
• 分子量: 513.634
• InChiKey: QOVKCSGEPAWUFJ-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 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：

  5-溴烟酸 、 3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-7-phenyl-heptanoic acid tert-butyl ester 生成 (3S)-3-[(5-bromopyridin-3-yl)formamido]-4-oxo-7-phenylheptanoic acid
  参考文献：
  名称：

  Nicotinyl aspartyl ketones as inhibitors of caspase-3

  摘要：

  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. Since P, aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of caspase-3. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00390-1
• 作为产物：
  描述：

  3-phenylpropyl-magnesium bromide 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-7-phenyl-heptanoic acid tert-butyl ester
  参考文献：
  名称：

  Nicotinyl aspartyl ketones as inhibitors of caspase-3

  摘要：

  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. Since P, aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of caspase-3. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00390-1

文献信息

• Synthesis of Fmoc-protected amino ketones bearing tert-butyl based side-chain protecting groups
  作者：Jesús Vázquez、Fernando Albericio

  DOI：10.1016/s0040-4039(02)01805-1

  日期：2002.10

  A variety of Fmoc-protected amino ketones have been prepared in good yields from amino acids by their transformation into thioesters of 2-mercaptopyridine and reaction of the resulting products with dialkylcuprates.

  通过将它们转化成2-巯基吡啶的硫代酯并使所得产物与二烷基铜酸酯反应，已从氨基酸以高收率制备了多种Fmoc保护的氨基酮。
• 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.
• Solid phase synthesis of selective caspase-3 peptide inhibitors
  作者：Erich L Grimm、Bruno Roy、Renee Aspiotis、Christopher I Bayly、Donald W Nicholson、Dita M Rasper、Johanne Renaud、Sophie Roy、John Tam、Paul Tawa、John P Vaillancourt、Steven Xanthoudakis、Robert J Zamboni

  DOI：10.1016/j.bmc.2004.01.007

  日期：2004.3

  A robust method for the solid phase synthesis of a series of selective caspase-3 peptide inhibitors is described. The inhibitors can be obtained after cleavage from the solid support without further purification. (C) 2004 Elsevier Ltd. All rights reserved.
• Nicotinyl aspartyl ketones as inhibitors of caspase-3
  作者：Elise Isabel、W.Cameron Black、Christopher I Bayly、Erich L Grimm、Marc K Janes、Daniel J McKay、Donald W Nicholson、Dita M Rasper、Johanne Renaud、Sophie Roy、John Tam、Nancy A Thornberry、John P Vaillancourt、Steven Xanthoudakis、Robert Zamboni

  DOI：10.1016/s0960-894x(03)00390-1

  日期：2003.7

  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. Since P, aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of caspase-3. (C) 2003 Elsevier Science Ltd. All rights reserved.