N-(3-chlorophenyl)-5-cyano-2-(((4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy)methyl)benzamide

• 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: N-(3-chlorophenyl)-5-cyano-2-(((4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy)methyl)benzamide
• 英文别名: N-(3-chlorophenyl)-5-cyano-2-{[(4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy]methyl}benzamide；N-(3-chlorophenyl)-5-cyano-2-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]benzamide
• 化学式: C₂₇H₂₀ClN₅O₂
• 分子量: 481.941
• InChiKey: DZYGQZQTEVKSFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氯苯胺 、 5-cyano-2-[(4-cyanophenyl)-(3-methyl-3H-imidazol-4-yl)methoxymethyl]benzoic acid 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以14.0 mg (48%)的产率得到N-(3-chlorophenyl)-5-cyano-2-(((4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy)methyl)benzamide
  参考文献：
  名称：

  Farnesyltransferase inhibitors

  摘要：

  取代咪唑和噻唑的化合物具有以下公式，对抑制法尼基转移酶具有用处。还公开了抑制法尼基转移酶的组合物和在患者中抑制法尼基转移酶的方法。

  公开号：

  US20020115640A1

文献信息

• Design, Synthesis, and Biological Activity of 4-[(4-Cyano-2-arylbenzyloxy)-(3-methyl-3<i>H</i>-imidazol-4-yl)methyl]benzonitriles as Potent and Selective Farnesyltransferase Inhibitors
  作者：Le Wang、Gary T. Wang、Xilu Wang、Yunsong Tong、Gerry Sullivan、David Park、Nicholas M. Leonard、Qun Li、Jerry Cohen、Wen-Zhen Gu、Haiying Zhang、Joy L. Bauch、Clarissa G. Jakob、Charles W. Hutchins、Vincent S. Stoll、Kennan Marsh、Saul H. Rosenberg、Hing L. Sham、Nan-Horng Lin

  DOI：10.1021/jm030434f

  日期：2004.1.1

  synthesized as selective farnesyltransferase inhibitors using structure-based design. X-ray cocrystal structures of compound 20-FTase-HFP and A313326-FTase-HFP confirmed our initial design. The decreased interaction between the aryl groups and Ser 48 in GGTase-I binding site could be one possible reason to explain the improved selectivity for this new series of FTase inhibitors. Medicinal chemistry efforts

  已经使用基于结构的设计合成了一系列新型的4-[（4-氰基-2-芳基苄氧基）-（3-甲基-3H-咪唑-4-基）甲基]苄腈作为选择性的法呢基转移酶抑制剂。化合物20-FTase-HFP和A313326-FTase-HFP的X射线共晶体结构证实了我们的初步设计。在GGTase-I结合位点中，芳基与Ser 48之间相互作用的减少可能是解释这种新系列FTase抑制剂选择性提高的可能原因。药物化学作用导致发现了具有强细胞活性（EC（50）= 3.5 nM）和杰出的药代动力学特征的化合物64（生物利用度96％，口服t（1/2）为18.4 h，0.19 L /（hx） kg）血浆清除率）。
• [EN] FARNESYLTRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DE FARNESYLTRANSFERASE
  申请人：ABBOTT LAB

  公开号：WO2002074747A1

  公开（公告）日：2002-09-26

  Substituted imidazoles and thiazoles having formula (I), are useful for inhibiting farnesyltransferase. Also disclosed are farnesyltransferase-inhibiting compositions and methods of inhibiting farnesyltransferase in a patient.

  具有公式（I）的替代咪唑和噻唑可用于抑制法尼醇转移酶。还公开了抑制法尼醇转移酶的组合物和在患者中抑制法尼醇转移酶的方法。
• Farnesyltransferase Inhibitors
  申请人：Claiborne K. Akiyo

  公开号：US20060264476A1

  公开（公告）日：2006-11-23

  Substituted imidazoles and thiazoles having the formula are useful for inhibiting farnesyltransferase. Also disclosed are farnesyltransferase-inhibiting compositions and methods of inhibiting farnesyltransferase in a patient.

  具有以下公式的取代咪唑和噻唑对于抑制法尼酰转移酶是有用的。还披露了抑制法尼酰转移酶的组合物和在患者中抑制法尼酰转移酶的方法。
• FARNESYLTRANSFERASE INHIBITORS
  申请人：Abbott Laboratories

  公开号：EP1339695A1

  公开（公告）日：2003-09-03
• Compounds Which Inhibits Protein Prenylation E.G. Geranylgeransferse or Farnesyltransferase Inhibitors for Treating Parkinson's Disease
  申请人：Schweighoffer Fabien

  公开号：US20080153758A1

  公开（公告）日：2008-06-26

  The invention relates to compounds and their uses, particularly in the pharmaceutical industry. The invention more specifically relates to new uses of compounds that inhibit the prenylation of proteins, in particular the geranylgeranyl and/or farnesyl modifications of proteins, for treating neurodegeneration involving oxidative stress and, more particularly, Parkinson's disease. The invention also relates to corresponding methods of treatment, and can be used in human subjects for preventive or curative treatment, either alone is or in combination with other active agents or treatments.