2-fluoro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)benzoic acid | 1538605-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-fluoro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)benzoic acid
• 英文别名: 2-Fluoro-4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]benzoic acid
• CAS: 1538605-86-5
• 化学式: C₁₈H₁₆F₄N₂O₂
• 分子量: 368.331
• InChiKey: MZTKVCZRYKYXAI-UHFFFAOYSA-N

物化性质

• 沸点：
  517.1±50.0 °C(predicted)
• 密度：
  1.378±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  8

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 、 2-fluoro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)benzoic 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61%的产率得到(R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-2-fluoro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)benzamide 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：

  2-氟-4-溴苯甲酸甲酯 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 50.0h， 生成 2-fluoro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)benzoic 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

• [EN] HDAC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA HDAC ET SES UTILISATIONS
  申请人：ENVIVO PHARMACEUTICALS INC

  公开号：WO2009137503A1

  公开（公告）日：2009-11-12

  Inhibitors of histone deacetylase, including compounds having a diazabicyclo[2.2.1]heptan-2-yl moiety are described together with methods for treating various disorders with such compounds.

  抑制组蛋白去乙酰化酶的抑制剂，包括具有二氮杂双环[2.2.1]庚烷-2-基基团的化合物，以及使用这些化合物治疗各种疾病的方法被描述。
• Dibenzo[b,f][1,4]oxazepine derivatives as inhibitors of histone deacetylase
  申请人：Methylgene, Inc.

  公开号：EP2343286A1

  公开（公告）日：2011-07-13

  This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula (I) wherein (B), Q, J, L and Z are as defined in the specification.

  本发明涉及抑制组蛋白去乙酰化酶的化合物。更具体地说，本发明提供了式 (I) 的化合物，其中 (B)、Q、J、L 和 Z 如说明书中所定义。
• Inhibitors of histone deacetylase
  申请人：MethylGene Inc.

  公开号：EP2489657A2

  公开（公告）日：2012-08-22

  This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula (I) wherein (B), Q, J, L and Z are as defined in the specification.

  本发明涉及抑制组蛋白去乙酰化酶的化合物。更具体地说，本发明提供了式 (I) 的化合物，其中 (B)、Q、J、L 和 Z 如说明书中所定义。
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：METHYGENE INC

  公开号：WO2008055068A2

  公开（公告）日：2008-05-08

  (EN) This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula (I) wherein (B), Q, J, L and Z are as defined in the specification.(FR) La présente invention concerne des composés permettant l'inhibition de l'histone désacétylase. L'invention concerne plus particulièrement des composés de formule (I) dans laquelle (B), Q, J, L et Z sont tels que définis dans le mémoire descriptif.
• <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.