1-(3-chlorophenyl)-4-[1-(3-((3-(2-hydroxy-1-ethoxy)phenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone

• 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: 1-(3-chlorophenyl)-4-[1-(3-((3-(2-hydroxy-1-ethoxy)phenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone
• 英文别名: 4-{5-[4-(3-Chloro-phenyl)-3-oxo-piperazin-1-ylmethyl]-imidazol-1-ylmethyl}-2-[3-(2-hydroxy-ethoxy)-phenoxy]-benzonitrile；4-[[5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]-2-[3-(2-hydroxyethoxy)phenoxy]benzonitrile
• 化学式: C₃₀H₂₈ClN₅O₄
• 分子量: 558.036
• InChiKey: MOLIDNVFZBNVNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氟-4-甲基苯腈 在 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 、 三氧化硫吡啶 、 三乙酰氧基硼氢化钠 、 caesium carbonate 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 二甲基亚砜 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(3-chlorophenyl)-4-[1-(3-((3-(2-hydroxy-1-ethoxy)phenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone
  参考文献：
  名称：

  Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

  摘要：

  A series of aryloxy substituted piperazinones with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to have potent inhibitory activity in vitro and are promising agents for the inhibition of Ki-Ras signaling. (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00240-2

文献信息

• Inhibitors of prenyl-protein transferase
  申请人：——

  公开号：US20020052380A1

  公开（公告）日：2002-05-02

  The present invention comprises piperazinone-containing compounds, which may be useful as inhibitors of prenyl-protein transferases, including farnesyl-protein transferase and geranylgeranyl-protein transferase type I. Such therapeutic compounds are useful in the treatment of cancer.

  本发明涵盖了含哌嗪酮类化合物，可能作为前甲基蛋白转移酶的抑制剂，包括法尼基-蛋白转移酶和戊二烯基-蛋白转移酶I型。这类治疗性化合物在癌症治疗中非常有用。
• TREATMENT OF PROTEINOPATHIES USING A FARNESYL TRANSFERASE INHIBITOR
  申请人：Lansbury, JR. Peter T.

  公开号：US20110294794A1

  公开（公告）日：2011-12-01

  Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject in need thereof a therapeutically effective amount of a farnesyl transferase inhibitor, wherein the amount is effective to inhibit the farnesylation of a non-Ras FTase substrate involved in the autophagy pathway without substantially affecting the farnesylation of Ras or other oncology related substrates. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

  本发明提供了一种低剂量法尼醇转移酶抑制剂及其制药组合物，用于治疗蛋白病。这些低剂量低于最初设计这些化合物用于肿瘤治疗所使用的剂量。治疗包括向需要治疗的受体中注射治疗有效量的法尼醇转移酶抑制剂，其中该量能够有效抑制参与自噬通路的非Ras FTase底物的法尼酰化，而不会对Ras或其他与肿瘤相关的底物的法尼酰化产生明显影响。按照本发明的治疗方法还可以包括乙酰胆碱酯酶抑制剂、神经营养因子受体激活剂、NMDA拮抗剂、淀粉样沉积抑制剂、抗精神病药物、抗抑郁药物、抗焦虑药物或抗氧化剂。
• Methods for the treatment of synucleinopathies (Lansbury)
  申请人：Lansbury T. Peter

  公开号：US20050277629A1

  公开（公告）日：2005-12-15

  Methods are provided of treating synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease and Multiple System Atrophy, comprising administering to a synucleinopathic subject one or more farnesyl transferase inhibitor compounds.
• Methods for the treatment of synucleinopathies
  申请人：Lansbury T. Peter

  公开号：US20070293539A1

  公开（公告）日：2007-12-20

  Methods are provided of treating synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease and Multiple System Atrophy, comprising administering to a synucleinopathic subject a farnesyl transferase inhibitor compound.
• Treatment of Lysosomal Storage Diseases
  申请人：Grammatopoulos Tom

  公开号：US20100184803A1

  公开（公告）日：2010-07-22

  Methods and compositions useful in the treatment or prevention of lysosomal storage diseases, such as Pompe's disease, Fabry's disease, Gaucher's disease, and Niemann-Pick disease, are provided. The treatment includes administering to a subject a farnesyl transferase inhibitor compound. The treatment may also include enzyme replacement therapy or gene therapy.