1-(2,4-dichlorophenyl)pentane-1,4-dione | 908292-38-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2,4-dichlorophenyl)pentane-1,4-dione
• CAS: 908292-38-6
• 化学式: C₁₁H₁₀Cl₂O₂
• 分子量: 245.105
• InChiKey: HYTRNMBQAKQGGK-UHFFFAOYSA-N

物化性质

• 熔点：
  37 °C(Solv: cyclohexane (110-82-7))
• 沸点：
  358.7±32.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 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：
  2

反应信息

• 作为反应物：
  描述：

  1-(2,4-dichlorophenyl)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-(2,4-Dichlorophenyl)-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：

  2,5-二氯苯甲醛 、 丁烯酮 在 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 三乙胺 作用下， 反应 5.0h， 以40%的产率得到1-(2,4-dichlorophenyl)pentane-1,4-dione
  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

文献信息

• A fluorescent target-guided Paal–Knorr reaction
  作者：Sachin B. Wagh、Vladimir Maslivetc、James J. La Clair、Alexander Kornienko

  DOI：10.1039/d0ra06962k

  日期：——

  It has become increasingly apparent that high-diversity chemical reactions play a significant role in the discovery of bioactive small molecules. Here, we describe an expanse of this paradigm, combining a ‘target-guided synthesis’ concept with Paal–Knorr chemistry applied to the preparation of fluorescent ligands for human prostaglandin-endoperoxide synthase (COX-2).

  越来越明显的是，高度多样性的化学反应在发现生物活性小分子方面发挥着重要作用。在这里，我们描述了这种范式的扩展，将“目标引导合成”概念与用于制备人前列腺素内过氧化物合酶 (COX-2) 的荧光配体的 Paal-Knorr 化学相结合。
• 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
• 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：——
• 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.