3,3'-difluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid | 1538605-81-0

• 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: 3,3'-difluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid
• 英文别名: 2-Fluoro-4-[3-fluoro-4-(trifluoromethyl)phenyl]benzoic acid；2-fluoro-4-[3-fluoro-4-(trifluoromethyl)phenyl]benzoic acid
• CAS: 1538605-81-0
• 化学式: C₁₄H₇F₅O₂
• 分子量: 302.2
• InChiKey: NOOUQDGDPDWELZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-2-amino-3-(1H-indol-3-yl)-N-(pyridin-4-yl)propanamide hydrochloric acid 、 3,3'-difluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid 、 三氟乙酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 二氯甲烷 、 甲醇 、 水 、 乙腈 为溶剂， 反应 1.25h， 以72%的产率得到(R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-3,3'-difluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxamide trifluoroacetate
  参考文献：
  名称：

  R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi

  摘要：

  Sterol 14 alpha-demethylase (CYP51) is an important therapeutic target for fungal and parasitic infections due to its key role in the biosynthesis of ergosterol, an essential component of the cell membranes of these pathogenic organisms. We report the development of potent and selective D-tryptophan-derived inhibitors of T. cruzi CYP51. Structural information obtained from the cocrystal structure of CYP51 and (R)-2, which is >1000-fold more potent than its enantiomer (S)-1, was used to guide design of additional analogues. The in vitro efficacy data presented here for (R)-2 (R)-8, together with preliminary in vitro pharmacokinetic data suggest that this new CYP51 inhibitor scaffold series has potential to deliver drug candidates for treatment of T. cruzi infections.

  DOI：

  10.1021/ml500010m
• 作为产物：
  描述：

  4-溴-2-氟苯甲酸 、 3-氟-4-(三氟甲基)苯硼酸 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三环己基膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以90%的产率得到3,3'-difluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid
  参考文献：
  名称：

  R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi

  摘要：

  Sterol 14 alpha-demethylase (CYP51) is an important therapeutic target for fungal and parasitic infections due to its key role in the biosynthesis of ergosterol, an essential component of the cell membranes of these pathogenic organisms. We report the development of potent and selective D-tryptophan-derived inhibitors of T. cruzi CYP51. Structural information obtained from the cocrystal structure of CYP51 and (R)-2, which is >1000-fold more potent than its enantiomer (S)-1, was used to guide design of additional analogues. The in vitro efficacy data presented here for (R)-2 (R)-8, together with preliminary in vitro pharmacokinetic data suggest that this new CYP51 inhibitor scaffold series has potential to deliver drug candidates for treatment of T. cruzi infections.

  DOI：

  10.1021/ml500010m

文献信息

• <i>R</i>-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against <i>Trypanosoma cruzi</i>
  作者：Jun Yong Choi、Claudia M. Calvet、Debora F. Vieira、Shamila S. Gunatilleke、Michael D. Cameron、James H. McKerrow、Larissa M. Podust、William R. Roush

  DOI：10.1021/ml500010m

  日期：2014.4.10

  Sterol 14 alpha-demethylase (CYP51) is an important therapeutic target for fungal and parasitic infections due to its key role in the biosynthesis of ergosterol, an essential component of the cell membranes of these pathogenic organisms. We report the development of potent and selective D-tryptophan-derived inhibitors of T. cruzi CYP51. Structural information obtained from the cocrystal structure of CYP51 and (R)-2, which is >1000-fold more potent than its enantiomer (S)-1, was used to guide design of additional analogues. The in vitro efficacy data presented here for (R)-2 (R)-8, together with preliminary in vitro pharmacokinetic data suggest that this new CYP51 inhibitor scaffold series has potential to deliver drug candidates for treatment of T. cruzi infections.