1-(4-fluorophenyl)-2-methyl-5-(2-chlorophenyl)-1H-pyrrole | 908292-40-0

• 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-chlorophenyl)-1H-pyrrole
• 英文别名: 2-(2-Chlorophenyl)-1-(4-fluorophenyl)-5-methylpyrrole
• CAS: 908292-40-0
• 化学式: C₁₇H₁₃ClFN
• 分子量: 285.748
• InChiKey: DPQGPUODNROJCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-2-methyl-5-(2-chlorophenyl)-1H-pyrrole 、 聚合甲醛 在 sodium hydroxide 、 水 作用下， 以 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 12.0h， 以83%的产率得到4-[[5-(2-Chlorophenyl)-1-(4-fluorophenyl)-2-methyl-pyrrol-3-yl]methyl]thiomorpholine
  参考文献：
  名称：

  WO2006/92822

  摘要：

  公开号：
• 作为产物：
  描述：

  2-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-chlorophenyl)-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

• WO2006/92822
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.