2-bromo-5-(tert-butyldiphenylsilyloxy)benzoic acid | 440105-95-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-bromo-5-(tert-butyldiphenylsilyloxy)benzoic acid
• 英文别名: 2-Bromo-5-[tert-butyl(diphenyl)silyl]oxybenzoic acid
• CAS: 440105-95-3
• 化学式: C₂₃H₂₃BrO₃Si
• 分子量: 455.423
• InChiKey: ZIBYPRJEAMLEPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-5-(tert-butyldiphenylsilyloxy)benzoic acid 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以73.3%的产率得到2-bromo-5-(tert-butyldiphenylsilyloxy)benzyl alcohol
  参考文献：
  名称：

  3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency

  摘要：

  A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.

  DOI：

  10.1021/jm010531d
• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 咪唑 、 三溴化硼 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2-bromo-5-(tert-butyldiphenylsilyloxy)benzoic acid
  参考文献：
  名称：

  3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency

  摘要：

  A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.

  DOI：

  10.1021/jm010531d

文献信息

• 3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency
  作者：Ian M. Bell、Steven N. Gallicchio、Marc Abrams、Lorena S. Beese、Douglas C. Beshore、Hema Bhimnathwala、Michael J. Bogusky、Carolyn A. Buser、J. Christopher Culberson、Joseph Davide、Michelle Ellis-Hutchings、Christine Fernandes、Jackson B. Gibbs、Samuel L. Graham、Kelly A. Hamilton、George D. Hartman、David C. Heimbrook、Carl F. Homnick、Hans E. Huber、Joel R. Huff、Kelem Kassahun、Kenneth S. Koblan、Nancy E. Kohl、Robert B. Lobell、Joseph J. Lynch,、Ronald Robinson、A. David Rodrigues、Jeffrey S. Taylor、Eileen S. Walsh、Theresa M. Williams、C. Blair Zartman

  DOI：10.1021/jm010531d

  日期：2002.6.1

  A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.