5-(4-iodobenzyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one | 636586-34-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-iodobenzyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one
• 英文别名: mtFabH inhibitor, 19；4-hydroxy-5-[(4-iodophenyl)methyl]-3,5-dimethylthiophen-2-one
• CAS: 636586-34-0
• 化学式: C₁₃H₁₃IO₂S
• 分子量: 360.216
• InChiKey: LGONZPJEKDSQJF-UHFFFAOYSA-N

物化性质

• 沸点：
  429.8±45.0 °C(Predicted)
• 密度：
  1.717±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-甲基噻酚-2-硼酸 、 5-(4-iodobenzyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 6.0h， 生成 mtFabH inhibitor, 36
  参考文献：
  名称：

  Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library

  摘要：

  Fifteen novel C5 analogues of thiolactomycin (13 biphenyl analogues and two biphenyl mimics) have been synthesised and assessed for their in vitro mtFabH and whole cell Mycobacterium bovis BCG activity, respectively. Analysis of the 15 compounds revealed that six possessed enhanced in vitro activity in a direct mtFabH assay. Encouragingly analogues 11, 12 and 13 gave a significant enhancement in in vitro activity against mtFabH. Analogue 13 (5-(4-methoxycarbonyl-biphenyl-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one) gave an IC50 value of 3 mu M compared to the parent drug thiolactomycin (75 mu M) against mtFabH. The biological analysis of this library reaffirms the requirement for a linear pi-rich system containing hydrogen bond accepting substituents attached to the para-position of the C5 biphenyl analogue to generate compounds with enhanced activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.082
• 作为产物：
  描述：

  4-碘苄基溴 、 3,5-dimethylthiotetronic acid 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 5-(4-iodobenzyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one
  参考文献：
  名称：

  Biphenyl-Based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme

  摘要：

  Analogues of the antibiotic thiolactomycin, with biphenyl-based 5-substituents, were found to have excellent in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-(4'-benzyloxy-biphen-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited approximately a 4-fold increased potency against this key condensing enzyme involved in M. tuberculosis mycolic acid biosynthesis, compared to thiolactomycin. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.015

文献信息

• Biphenyl-Based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme
  作者：Suzanne J Senior、Petr A Illarionov、Sudagar S Gurcha、Ian B Campbell、Merrill L Schaeffer、David E Minnikin、Gurdyal S Besra

  DOI：10.1016/j.bmcl.2003.08.015

  日期：2003.11

  Analogues of the antibiotic thiolactomycin, with biphenyl-based 5-substituents, were found to have excellent in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-(4'-benzyloxy-biphen-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited approximately a 4-fold increased potency against this key condensing enzyme involved in M. tuberculosis mycolic acid biosynthesis, compared to thiolactomycin. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library
  作者：Veemal Bhowruth、Alistair K. Brown、Suzanne J. Senior、John S. Snaith、Gurdyal S. Besra

  DOI：10.1016/j.bmcl.2007.07.082

  日期：2007.10

  Fifteen novel C5 analogues of thiolactomycin (13 biphenyl analogues and two biphenyl mimics) have been synthesised and assessed for their in vitro mtFabH and whole cell Mycobacterium bovis BCG activity, respectively. Analysis of the 15 compounds revealed that six possessed enhanced in vitro activity in a direct mtFabH assay. Encouragingly analogues 11, 12 and 13 gave a significant enhancement in in vitro activity against mtFabH. Analogue 13 (5-(4-methoxycarbonyl-biphenyl-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one) gave an IC50 value of 3 mu M compared to the parent drug thiolactomycin (75 mu M) against mtFabH. The biological analysis of this library reaffirms the requirement for a linear pi-rich system containing hydrogen bond accepting substituents attached to the para-position of the C5 biphenyl analogue to generate compounds with enhanced activity. (c) 2007 Elsevier Ltd. All rights reserved.