Aceton-(4-fluor-phenylhydrazon) | 1077-22-1

• 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: Aceton-(4-fluor-phenylhydrazon)
• 英文别名: 4-fluoro-N-(propan-2-ylideneamino)aniline
• CAS: 1077-22-1
• 化学式: C₉H₁₁FN₂
• mdl: MFCD22054263
• 分子量: 166.198
• InChiKey: QDTJDKXHZJXPIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  24.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2928000090

反应信息

• 作为反应物：
  描述：

  Aceton-(4-fluor-phenylhydrazon) 在 正丁基锂 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.5h， 生成 methyl 4-[[2-(5-fluoro-2-methyl-1H-indol-3-yl)ethyl]sulfonyl]benzoate
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882
• 作为产物：
  描述：

  4-氟苯肼盐酸盐 、 丙酮 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 Aceton-(4-fluor-phenylhydrazon)
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882

文献信息

• 1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS
  申请人：PFIZER INC.

  公开号：US20170029390A1

  公开（公告）日：2017-02-02

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.

  本发明提供了部分I式化合物及其药学上可接受的盐；制备所用的中间体；以及含有这种化合物或盐的组合物，以及它们用于治疗MAGL介导的疾病和障碍，包括但不限于疼痛，炎症性疾病，创伤性脑损伤，抑郁症，焦虑症，阿尔茨海默病，代谢紊乱，中风或癌症。
• Kilany, Yeldez El; Mousaad, Ahmed; Hamid, Hamida Abdel, Gazzetta Chimica Italiana, 1988, vol. 118, # 9, p. 617 - 622
  作者：Kilany, Yeldez El、Mousaad, Ahmed、Hamid, Hamida Abdel、Ashry, El Sayed H. El

  DOI：——

  日期：——
• Ray, Partha S.; Hank, Richard F., Journal of Heterocyclic Chemistry, 1990, vol. 27, # 7, p. 2017 - 2020
  作者：Ray, Partha S.、Hank, Richard F.

  DOI：——

  日期：——
• RAY, PARTHA S.;HANK, RICHARD F., J. HETEROCYCL. CHEM., 27,(1990) N, C. 2017-2020
  作者：RAY, PARTHA S.、HANK, RICHARD F.

  DOI：——

  日期：——
• EL, KILANY YELDEZ;MOUSAAD, AHMED;HAMID, HAMIDA ABDEL;EL, ASHRY EL SAYED H+, GAZZ. CHIM. ITAL., 118,(1988) N 9, C. 617-621
  作者：EL, KILANY YELDEZ、MOUSAAD, AHMED、HAMID, HAMIDA ABDEL、EL, ASHRY EL SAYED H+

  DOI：——

  日期：——