methyl [1-(4-Cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetate | 445434-57-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl [1-(4-Cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetate
• 英文别名: methyl 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate；methyl 2-[3-[(4-cyano-3-fluorophenyl)methyl]imidazol-4-yl]acetate
• CAS: 445434-57-1
• 化学式: C₁₄H₁₂FN₃O₂
• 分子量: 273.267
• InChiKey: ZNILCSXUAAIDMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl [1-(4-Cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 [1-(4-cyano-3-fluorophenyl)-1H-imidazol-5-yl]acetic 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
• 作为产物：
  描述：

  甲基(1-trityl-1H-imidazol-4-yl)乙酸酯 以 甲醇 、 乙腈 为溶剂， 生成 methyl [1-(4-Cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetate
  参考文献：
  名称：

  Inhibitors of prenyl-protein transferase

  摘要：

  本发明涉及抑制萜基-蛋白转移酶（FTase）和致癌基因蛋白Ras的大环化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制萜基-蛋白转移酶和致癌基因蛋白Ras的方法。

  公开号：

  US06441017B1

文献信息

• US6358985B1
  申请人：——

  公开号：US6358985B1

  公开（公告）日：2002-03-19