1-(2-fluorophenyl)pentane-1,4-dione | 723296-62-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-fluorophenyl)pentane-1,4-dione
• CAS: 723296-62-6
• 化学式: C₁₁H₁₁FO₂
• 分子量: 194.206
• InChiKey: CMAJDHODPXOKCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-fluorophenyl)pentane-1,4-dione 在 对甲苯磺酸 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 13.0h， 生成 4-[[5-(2-Fluorophenyl)-1-(4-fluorophenyl)-2-methyl-pyrrol-3-yl]methyl]thiomorpholine
  参考文献：
  名称：

  Antimycobacterial Agents. Novel Diarylpyrrole Derivatives of BM212 Endowed with High Activity toward Mycobacterium tuberculosis and Low Cytotoxicity

  摘要：

  On the basis of suggestions derived either from a pharmacophoric model for antitubercular agents or from a structure-activity relationship analysis of many pyrroles previously described by us, we report here the design and synthesis of new analogues of 1,5-(4-chlorophenyl)-2-methyl-3-(4-methylpiperazin-1-yl)methyl-1H- pyrrole (BM212). Various substituents with different substitution patterns were added to both positions 1 and 5 of the pyrrole nucleus to evaluate their influence on the activity toward Mycobacterium tuberculosis (MTB) and atypical mycobacteria. Biological data showed that, although some nontuberculosis mycobacterial strains were found to be sensitive, MIC values were higher than those found toward MTB. The best compound (1-(4-fluorophenyl)-2-methyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole, 5) possessed a MIC of 0.4 mu g/mL (better than BM212 and streptomycin) and a very high protection index (160), better than BM212, isoniazid, and streptomycin ( 6, 128, and 128, respectively). Finally, molecular modeling studies were performed to rationalize the activity of the new compounds in terms of both superposition onto a pharmacophoric model for antitubercular compounds and their hydrophobic character.

  DOI：

  10.1021/jm0602662
• 作为产物：
  描述：

  3-(2-氟苯基)丙-2-炔酸 、 丙酮 在 copper(II) perchlorate hexahydrate 、 水 、 manganese(III) triacetate dihydrate 、 碳酸氢钠 、 过氧化苯甲酰 作用下， 反应 6.0h， 以71%的产率得到1-(2-fluorophenyl)pentane-1,4-dione
  参考文献：
  名称：

  铜催化炔基羧酸的脱羧氧化烷基化：γ-二酮和γ-乙腈的合成

  摘要：

  通过直接的C（sp 3）-H键官能化来构建新的C-C键和C-O双键的新型铜催化的炔基羧酸与酮和烷基腈的脱羧氧化烷基化反应得到了发展。这种转变的特征是广泛的官能团相容性和易于使用的试剂的使用，从而为γ-二酮和γ-酮腈提供了一种通用方法。提出了一种可能的机制。

  DOI：

  10.1021/acs.orglett.9b00520

文献信息

• Design, synthesis and evaluation of 1-(1,5-bis(4-substituted phenyl)-2-methyl-1<i>H</i>-pyrrol-3-yl)-<i>N</i>-methylmethanamines as SERT inhibitors with potential antidepressant action
  作者：Anjani Uma Rani Wunnava、Sony Priya Kurati、Kilari Eswar Kumar、Murali Krishna Kumar Muthyala

  DOI：10.1039/d2md00243d

  日期：——

  antidepressant drugs, we designed, synthesized and screened twelve 1-(1,5-bis(4-substituted phenyl)-2-methyl-1H-pyrrol-3-yl)-N-methylmethanamines (SA-1 to SA-12) for in vitro SERT inhibition and in vivo antidepressant activity. The compounds were screened for in vitro 5HT reuptake inhibition using the platelet model. Among the screened compounds, (1-(1,5-bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)-N-methylmethanamine)

  BM212 是一种有效的抗结核药物，其药效特征与抗抑郁药物舍曲林相似。对 BM212 上的 DrugBank 数据库进行基于形状的虚拟筛选，鉴定出了几种具有明显 Tanimoto 评分的 CNS 药物。对接模拟还确定了 BM212 对血清素再摄取转运蛋白 (SERT) 的选择性，对接分数为 -6.51 kcal mol -1。基于舍曲林和其他抗抑郁药物的SAR数据，我们设计、合成并筛选了12个1-(1,5-双(4-取代苯基)-2-甲基-1H-吡咯-3-基) -N -甲基甲胺（SA-1 至 SA-12）用于体外SERT 抑制和体内抗抑郁活性。使用血小板模型筛选化合物的体外5HT 再摄取抑制作用。在筛选的化合物中，(1-(1,5-双(4-氯苯基)-2-甲基-1H-吡咯-3-基) -N-甲基甲胺)表现出与标准药物舍曲林（吸光度 0.22）。BM212 对 5-HT 摄取有影响，尽管与标准品相比较弱（吸光度
• Antimycobacterial compounds. New pyrrole derivatives of BM212
  作者：Mariangela Biava、Giulio Cesare Porretta、Delia Deidda、Raffaello Pompei、Andrea Tafi、Fabrizio Manetti

  DOI：10.1016/j.bmc.2003.12.037

  日期：2004.3

  We have identified BM212 as a lead compound among a series of pyrrole derivatives with good in vitro activity against mycobacteria and candidae. First studies led us to synthesize some pyrrole compounds in which the thiomorpholine fragment was present. Some compounds revealed very active and these findings prompted us to prepare new pyrrole derivatives 2-15 in the hope of increasing the activity. The microbiological data showed interesting in vitro activity against Mycobacterium tuberculosis and atypical mycobacteria. (C) 2004 Elsevier Ltd. All rights reserved.
• Discovery of selective and potent anti-tubercular activity in arylpentane-1,4-diones
  作者：Umarani, W. A.、Sony, K. P.、Hymavathi, K. V.、Kumar, M. Murali Krishna

  DOI：10.56042/ijc.v61i4.62561

  日期：——
• Copper-Catalyzed Decarboxylative Oxyalkylation of Alkynyl Carboxylic Acids: Synthesis of γ-Diketones and γ-Ketonitriles
  作者：Yi Li、Jia-Qi Shang、Xiang-Xiang Wang、Wen-Jin Xia、Tao Yang、Yangchun Xin、Ya-Min Li

  DOI：10.1021/acs.orglett.9b00520

  日期：2019.4.5

  A novel copper-catalyzed decarboxylative oxyalkylation of alkynyl carboxylic acids with ketones and alkylnitriles via direct C(sp3)–H bond functionalization to construct new C–C bonds and C–O double bonds was developed. This transformation is featured by wide functional group compatibility and the use of readily available reagents, thus affording a general approach to γ-diketones and γ-ketonitriles

  通过直接的C（sp 3）-H键官能化来构建新的C-C键和C-O双键的新型铜催化的炔基羧酸与酮和烷基腈的脱羧氧化烷基化反应得到了发展。这种转变的特征是广泛的官能团相容性和易于使用的试剂的使用，从而为γ-二酮和γ-酮腈提供了一种通用方法。提出了一种可能的机制。
• Antimycobacterial Agents. Novel Diarylpyrrole Derivatives of BM212 Endowed with High Activity toward Mycobacterium tuberculosis and Low Cytotoxicity
  作者：Mariangela Biava、Giulio Cesare Porretta、Giovanna Poce、Sibilla Supino、Delia Deidda、Raffaello Pompei、Paola Molicotti、Fabrizio Manetti、Maurizio Botta

  DOI：10.1021/jm0602662

  日期：2006.8.1

  On the basis of suggestions derived either from a pharmacophoric model for antitubercular agents or from a structure-activity relationship analysis of many pyrroles previously described by us, we report here the design and synthesis of new analogues of 1,5-(4-chlorophenyl)-2-methyl-3-(4-methylpiperazin-1-yl)methyl-1H- pyrrole (BM212). Various substituents with different substitution patterns were added to both positions 1 and 5 of the pyrrole nucleus to evaluate their influence on the activity toward Mycobacterium tuberculosis (MTB) and atypical mycobacteria. Biological data showed that, although some nontuberculosis mycobacterial strains were found to be sensitive, MIC values were higher than those found toward MTB. The best compound (1-(4-fluorophenyl)-2-methyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole, 5) possessed a MIC of 0.4 mu g/mL (better than BM212 and streptomycin) and a very high protection index (160), better than BM212, isoniazid, and streptomycin ( 6, 128, and 128, respectively). Finally, molecular modeling studies were performed to rationalize the activity of the new compounds in terms of both superposition onto a pharmacophoric model for antitubercular compounds and their hydrophobic character.