[1-(4-cyano-3-fluorophenyl)-1H-imidazol-5-yl]acetic acid | 368435-73-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [1-(4-cyano-3-fluorophenyl)-1H-imidazol-5-yl]acetic acid
• 英文别名: [1-(4-cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetic acid；2-[3-[(4-Cyano-3-fluorophenyl)methyl]imidazol-4-yl]acetic acid
• CAS: 368435-73-8
• 化学式: C₁₃H₁₀FN₃O₂
• 分子量: 259.24
• InChiKey: PYGNSUAVNSAFRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [1-(4-cyano-3-fluorophenyl)-1H-imidazol-5-yl]acetic acid 在 caesium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 19-Methyl-15,18-dioxo-2-oxa-9,11,16,19-tetrazapentacyclo[18.6.2.13,7.09,13.024,28]nonacosa-1(27),3,5,7(29),10,12,20,22,24(28),25-decaene-4-carbonitrile
  参考文献：
  名称：

  Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of farnesyl-protein transferase

  摘要：

  A series of amino acid-based linkers was used to investigate the effects of various substituents upon the potency, pharmacokinetic properties, and conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a result of the studies described herein, highly potent FTIs with improved pharmacokinetic profiles have been identified. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00340-7
• 作为产物：
  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

文献信息

• INHIBITORS OF PRENYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP1090011A1

  公开（公告）日：2001-04-11
• EP1090011A4
  申请人：——

  公开号：EP1090011A4

  公开（公告）日：2005-04-06
• US6410534B1
  申请人：——

  公开号：US6410534B1

  公开（公告）日：2002-06-25
• US6441017B1
  申请人：——

  公开号：US6441017B1

  公开（公告）日：2002-08-27
• [EN] INHIBITORS OF PRENYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE PRENYL-PROTEINE TRANSFERASE
  申请人：MERCK & CO INC

  公开号：WO2000001701A1

  公开（公告）日：2000-01-13

  The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.