1-(4-fluorophenyl)-2-methyl-5-(2,4-dichlorophenyl)-1H-pyrrole | 908292-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(4-fluorophenyl)-2-methyl-5-(2,4-dichlorophenyl)-1H-pyrrole
• CAS: 908292-45-5
• 化学式: C₁₇H₁₂Cl₂FN
• 分子量: 320.193
• InChiKey: QAWUAYAIUHBIAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  4.93
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 1-(4-fluorophenyl)-2-methyl-5-(2,4-dichlorophenyl)-1H-pyrrole 、 聚合甲醛 在 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 8.0h， 以65%的产率得到1-[[5-(2,4-Dichlorophenyl)-1-(4-fluorophenyl)-2-methyl-pyrrol-3-yl]methyl]-4-methyl-piperazine
  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 在 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 对甲苯磺酸 、 三乙胺 作用下， 反应 10.0h， 生成 1-(4-fluorophenyl)-2-methyl-5-(2,4-dichlorophenyl)-1H-pyrrole
  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。