(3-氟-苯基)-哌嗪-1-甲酮 | 179334-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (3-氟-苯基)-哌嗪-1-甲酮
• 中文别名: 3-氟苯-哌嗪-1-甲酮
• 英文名称: (3-fluorophenyl)(piperazin-1-yl)methanone
• 英文别名: 1-(3-Fluorobenzoyl)piperazine；(3-fluorophenyl)-piperazin-1-ylmethanone
• CAS: 179334-10-2
• 化学式: C₁₁H₁₃FN₂O
• mdl: MFCD01828965
• 分子量: 208.235
• InChiKey: KXFXHXPKGLLUGX-UHFFFAOYSA-N

物化性质

• 沸点：
  352.8±37.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi

反应信息

• 作为反应物：
  描述：

  (3-氟-苯基)-哌嗪-1-甲酮 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 34.0h， 生成 1-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-2-(4-(3-fluorobenzoyl)piperazin-1-yl)ethan-1-one
  参考文献：
  名称：

  Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer’s disease

  摘要：

  During the last decade, the one drug-one target strategy has resulted to be inefficient in facing diseases with complex ethiology like Alzheimer's disease and many others. In this context, the multitarget paradigm has emerged as a promising strategy. Based on this consideration, we aim to develop novel molecules as promiscuous ligands acting in two or more targets at the same time. For such purpose, a new series of indolylpropyl-piperazinyl oxoethyl-benzamido piperazines were synthesized and evaluated as multitarget-directed drugs for the serotonin transporter (SERT) and acetylcholinesterase (AChE). The ability to decrease beta-amyloid levels as well as cell toxicity of all compounds were also measured. In vitro results showed that at least four compounds displayed promising activity against SERT and AChE. Compounds 18 and 19 (IC50 = 3.4 and 3.6 mu M respectively) exhibited AChE inhibition profile in the same order of magnitude as donepezil (DPZ, IC50 = 2.17 mu M), also displaying nanomolar affinity in SERT. Moreover, compounds 17 and 24 displayed high SERT affinities (IC50 = 9.2 and 1.9 nM respectively) similar to the antidepressant citalopram, and significant micromolar AChE activity at the same time. All the bioactive compounds showed a low toxicity profile in the range of concentrations studied. Molecular docking allowed us to rationalize the binding mode of the synthesized compounds in both targets. In addition, we also show that compounds 11 and 25 exhibit significant beta-amyloid lowering activity in a cell-based assay, 11 (50% inhibition, 10 mu M) and 25 (35% inhibition, 10 mu M).These results suggest that indolylpropyl benzamidopiperazines based compounds constitute promising leads for a multitargeted approach for Alzheimers disease. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112368
• 作为产物：
  描述：

  tert-butyl 4-(3-fluorobenzoyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3-氟-苯基)-哌嗪-1-甲酮
  参考文献：
  名称：

  展望可药物治疗的人碳酸酐酶同工型的活性位点腔的边缘。

  摘要：

  我们报告了一系列的取代的4-（4-芳酰基哌嗪-1-羰基）苯磺酰胺（5a-s）的合成和生化评估，这些药物被开发为可药用的碳酸酐酶（CA）亚型的抑制剂，作为鉴定新疗法的工具。X射线晶体学证实，这类苯磺酰胺通过苯磺酰胺部分对金属离子的典型锚定和活性中心腔中部/顶部区域的尾部介导识别而与CA结合。化合物5e（R = 2-Cl）对脑表达的hCA VII具有相关的选择性。对于抑制剂5o（R = 3-NO2），发现对肿瘤表达的hCA IX / hCA XII的结合亲和力和选择性优于无处不在的hCA I / hCA II的最佳平衡。

  DOI：

  10.1021/acsmedchemlett.0c00062

文献信息

• Certain substituted 1-aryl-3-piperazin-1'-yl propanones to treat
  申请人：Molecular Geriatrics Corporation

  公开号：US05658909A1

  公开（公告）日：1997-08-19

  Disclosed are compounds of formula I: ##STR1## or the pharmaceutically acceptable salts thereof wherein X is a carbonyl, sulfonyl, methylene, or methylene substituted with optionally substituted phenyl; Z is nitrogen or CH; Ar.sub.1 and Ar.sub.2 independently represent aryl groups; and Y is hydrogen; or Y and R.sub.1 or R.sub.2 together represent CH.sub.2 ; CH.sub.2 CH.sub.2 ; CH.sub.2 O; CH.sub.2 S forming a five or six membered ring and such ring may be optionally substituted with loweralkyl or phenyl; or pharmaceutically acceptable salts thereof, useful in the treatment of neoplastic diseases, and bacterial or fungal infections, and for preventing or decreasing the production of abnormally phosphorylated paired helical filament (PHF) epitopes associated with Alzheimer's Disease and, therefore for treating Alzheimer's Disease.

  揭示了以下式I的化合物：##STR1##或其药学上可接受的盐，其中X是羰基、磺酰基、亚甲基或亚甲基，或者亚甲基上带有可选择取代的苯基；Z是氮或CH；Ar.sub.1和Ar.sub.2分别代表芳基；Y是氢；或者Y和R.sub.1或R.sub.2一起代表CH.sub.2；CH.sub.2 CH.sub.2；CH.sub.2 O；CH.sub.2 S形成五元或六元环，该环可以选择性地取代为较低的烷基或苯基；或其药学上可接受的盐，用于治疗肿瘤性疾病，细菌或真菌感染，并用于预防或减少与阿尔茨海默病相关的异常磷酸化成对螺旋丝（PHF）表位的产生，因此用于治疗阿尔茨海默病。
• Substituted 1-aryl-3-piperazin-1'-yl propanones
  申请人：Molecular Geriatrics Corporation

  公开号：US05693804A1

  公开（公告）日：1997-12-02

  Disclosed are compounds of formula I: ##STR1## wherein X is a carbonyl, sulfonyl, methylene, or methylene substituted with optionally substituted phenyl; Z is nitrogen or CH; Ar.sub.1 and Ar.sub.2 independently represent aryl groups; and Y is hydrogen; or Y and R.sub.1 or R.sub.2 together represent CH.sub.2 ;CH.sub.2 CH.sub.2 ; CH.sub.2 O; CH.sub.2 S forming a five or six membered ring and such ring may be optionally substituted with loweralkyl or phenyl; or the pharmaceutically acceptable salts thereof, useful in the treatment of neoplastic diseases, and bacterial or fungal infections, and in preventing or decreasing the production of abnormally phosphorylated paired helical filament (PHF) epitopes associated with Alzheimer's Disease and, therefore, useful for treating Alzheimer's Disease.

  揭示了以下式I的化合物：##STR1## 其中X是羰基、磺酰基、亚甲基或亚甲基，或者亚甲基上带有可选择取代的苯基；Z是氮或CH；Ar.sub.1和Ar.sub.2分别代表芳基；Y是氢；或者Y和R.sub.1或R.sub.2一起代表CH.sub.2；CH.sub.2 CH.sub.2；CH.sub.2 O；CH.sub.2 S形成五元或六元环，该环可以选择性地用较低烷基或苯基取代；或其药学上可接受的盐，用于治疗肿瘤性疾病，细菌或真菌感染，并预防或减少与阿尔茨海默病相关的异常磷酸化成对螺旋丝（PHF）表位的产生，因此，用于治疗阿尔茨海默病。
• Late Stage Functionalization of Secondary Amines via a Cobalt-Catalyzed Electrophilic Amination of Organozinc Reagents
  作者：Simon Graßl、Yi-Hung Chen、Clémence Hamze、Carl Phillip Tüllmann、Paul Knochel

  DOI：10.1021/acs.orglett.8b03787

  日期：2019.1.18

  A general preparation of polyfunctional hydroxylamine benzoates from the corresponding secondary amines is reported. This convenient synthesis allows the setup of a late-stage functionalization of various secondary amines, including pharmaceuticals and peptidic derivatives. Thus, a cross-coupling of hydroxylamine benzoates with various alkyl-, aryl-, and heteroaryl-zinc chlorides in the presence of

  据报道，由相应的仲胺制备多官能羟胺苯甲酸酯的一般方法。这种方便的合成方法可以建立各种仲胺（包括药物和肽衍生物）的后期官能化功能。因此，在5 mol％CoCl 2（25°C，2 h）存在下，羟胺苯甲酸酯与各种烷基氯化锌，芳基氯化锌和杂芳基氯化锌的交叉偶联提供了一系列多官能叔胺。该方法用于制备戊氟哌啶和吉哌隆。
• NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
  申请人：Sundaresan Kumar

  公开号：US20090239848A1

  公开（公告）日：2009-09-24

  The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.

  本发明涉及作为硬脂酰辅酶A去饱和酶抑制剂的哌嗪衍生物。该发明还涉及制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。
• N-substituted benzimidazolyl c-Kit inhibitors and combinatorial benzimidazole library
  申请人：Crew Philip Andrew

  公开号：US20060116402A1

  公开（公告）日：2006-06-01

  Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, are useful in the treatment of tumors. Combinatorial libraries composed of compounds represented by Formula (I) or benzimidazole compounds represented by Formula (II): are useful in providing compounds to assay for such therapeutically useful compounds.

  式(I)表示的化合物：或其药学上可接受的盐或N-氧化物，在肿瘤治疗中具有用途。由式(I)表示的化合物或式(II)表示的苯并咪唑化合物组成的组合库：在提供用于筛选此类治疗上有用的化合物的化合物方面具有用途。