4-(2,4-difluorophenyl)but-3-en-2-one | 144865-37-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 4-(2,4-difluorophenyl)but-3-en-2-one
• CAS: 144865-37-2
• 化学式: C₁₀H₈F₂O
• 分子量: 182.17
• InChiKey: GHLZMZVZIRWHQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2,4-difluorophenyl)but-3-en-2-one 、 丙二酸二乙酯 在 sodium ethanolate 、 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 、 乙醚 为溶剂， 反应 24.0h， 生成 5-(2,4-difluoro-phenyl)-cyclohexane-1,3-dione
  参考文献：
  名称：

  Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 months. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiology. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives. A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (26) with an EC(50) of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound 26 did not exhibit any significant life span extension in the ALS mouse model. It was found that, although 26 was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (71 and 73) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of 26 in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.039
• 作为产物：
  描述：

  2,4-二氟苯甲醛 、 1-三苯基膦-2-丙酮 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 4-(2,4-difluorophenyl)but-3-en-2-one
  参考文献：
  名称：

  Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 months. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiology. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives. A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (26) with an EC(50) of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound 26 did not exhibit any significant life span extension in the ALS mouse model. It was found that, although 26 was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (71 and 73) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of 26 in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.039

文献信息

• PYRROLIDINE ETHER DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS
  申请人：Jablonski Philippe

  公开号：US20090306043A1

  公开（公告）日：2009-12-10

  The present invention relates to compounds of formula I wherein R 1 , R 2 , R 3 , R′, Ar, m, n, and o are as defined herein. The invention also relates to pharmaceutical compositions containing compounds of formula I and methods for the manufacture of such compounds and compositions. Compounds of the invention are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

  本发明涉及式I的化合物，其中R1、R2、R3、R′、Ar、m、n和o如本文所定义。该发明还涉及含有式I化合物的药物组合物，以及制备这种化合物和组合物的方法。本发明的化合物是用于治疗抑郁症、疼痛、精神病、帕金森病、精神分裂症、焦虑和注意力缺陷多动障碍（ADHD）的高潜力NK-3受体拮抗剂。
• PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS
  申请人：Jablonski Philippe

  公开号：US20090042896A1

  公开（公告）日：2009-02-12

  The invention relates to a compound of formula I wherein Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , n, o, p, and q are as defined herein and to a pharmaceutically active salt thereof, including all stereoisomeric forms, individual diastereoisomers and enantiomers of the compound of formula (I) as well as racemic and non-racemic mixtures thereof. The compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

  该发明涉及一种化合物，其化学式为I，其中Ar1、Ar2、R1、R2、R3、R4、n、o、p和q如本文所定义，并且涉及其药用活性盐，包括化合物(I)的所有立体异构形式、单个对映体异构体和对映体，以及其外消旋和非外消旋混合物。这些化合物是高潜力的NK-3受体拮抗剂，用于治疗抑郁症、疼痛、精神病、帕金森病、精神分裂症、焦虑和注意力缺陷多动障碍（ADHD）。
• CRTH2 MODULATORS
  申请人：MERMERIAN Ara

  公开号：US20110150834A1

  公开（公告）日：2011-06-23

  Modulators of CRTH2, particularly antagonists of CRTH2, that are useful for treating various disorders, including asthma and respiratory disorders are disclosed. The compounds fall within a genus described by formula I:

  CRTH2的调节剂，特别是CRTH2的拮抗剂，可用于治疗各种疾病，包括哮喘和呼吸系统疾病。这些化合物属于由公式I描述的一类物质。
• Iridium-catalyzed reductive etherification of α,β-unsaturated ketones and aldehydes with alcohols
  作者：Lu Ouyang、Yanping Xia、Rui Miao、Jianhua Liao、Renshi Luo

  DOI：10.1039/d2ob00122e

  日期：——

  An iridium complex-catalyzed reductive etherification of α,β-unsaturated ketones and aldehydes with primary alcohols is presented, affording allyl ethers in excellent yields. Deuterated and control experiments showed that this etherification transformation proceeded through a cascade transfer hydrogenation and alcohol condensation process. Moreover, the utility of this protocol is evidenced by the

  提出了一种铱络合物催化的α,β-不饱和酮和醛与伯醇的还原醚化反应，以优异的收率提供烯丙基醚。氘代和对照实验表明，这种醚化转化是通过级联转移氢化和醇缩合过程进行的。此外，克级性能证明了该协议的实用性。
• US8063075B2
  申请人：——

  公开号：US8063075B2

  公开（公告）日：2011-11-22