4'-氟-3-联苯乙酸 | 327107-49-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4'-氟-3-联苯乙酸
• 英文名称: 3-(4-fluorophenyl)phenylacetic acid
• 英文别名: 2-(4'-Fluoro-[1,1'-biphenyl]-3-yl)acetic acid；2-[3-(4-fluorophenyl)phenyl]acetic acid
• CAS: 327107-49-3
• 化学式: C₁₄H₁₁FO₂
• 分子量: 230.239
• InChiKey: KEHXYIKRLCYNJX-UHFFFAOYSA-N

物化性质

• 沸点：
  381.9±22.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  3
• 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：
  3

反应信息

• 作为反应物：
  描述：

  4'-氟-3-联苯乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 3-(4-fluorophenyl)phenylacetic acid chloride
  参考文献：
  名称：

  Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the Trypanosoma brucei Soluble Vacuolar Pyrophosphatase

  摘要：

  Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from similar to 2 to 850 mu M. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R-2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC(50) error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of similar to 2.6 error in IC50 prediction. For CoMSIA, the rms pIC(50) error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.

  DOI：

  10.1021/jm058220g

文献信息

• [EN] 3,4-DIARYLPYRAZOLES AND THEIR USE IN THE THERAPY OF CANCER<br/>[FR] 3,4-DIARYLPYRAZOLES ET LEUR UTILISATION EN THERAPIE ANTI-CNCEREUSE
  申请人：RIBOTARGETS LTD

  公开号：WO2003055860A1

  公开（公告）日：2003-07-10

  The present invention pertains to the use of certain 3,4-diarylpyrazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar3 is independently: a C5-20aryl group, and is optionally substituted; Ar4 is independently: a C5-20aryl group, and is optionally substituted; R5 is independently: hydrogen; halo; hydroxy; ether; formyl; acyl; carboxy; ester; acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamido; C1-7alkyl; C3-20heterocycyl; or C5-20aryl; RN is independently: -H; C1-7alkyl; C3-20heterocycyl; or, C5-20aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, such compounds for medical use, such compounds for use in the treatment of conditions mediated by HSP90, including, for example, cancer, and use of such compounds in the preparation of medicaments for such treatments.

  本发明涉及使用式(I)的特定3,4-二芳基吡唑化合物，无论是体外还是体内，以抑制热休克蛋白90（HSP90）的作用，并用于治疗由HSP90介导的疾病，例如癌症；其中：Ar3独立地表示：C5-20芳基基团，且可选地被取代；Ar4独立地表示：C5-20芳基基团，且可选地被取代；R5独立地表示：氢；卤素；羟基；醚；甲酰基；酰基；羧基；酯基；酰氧基；氧羰基氧基；酰胺基；酰胺氧基；氨基羰氧基；四唑基；氨基；硝基；氰基；偶氮基；硫醇基；硫醚基；磺酰胺基；C1-7烷基；C3-20杂环基；或C5-20芳基；RN独立地表示：-H；C1-7烷基；C3-20杂环基；或C5-20芳基；以及其药学上可接受的盐，溶剂化合物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及这些化合物，包含这些化合物的制药组合物，用于医疗用途的这些化合物，用于治疗由HSP90介导的疾病，例如癌症的这些化合物，以及使用这些化合物制备此类治疗药物的用途。
• 3,4-diarylpyrazoles and their use in the therapy of cancer
  申请人：Drysdale James Martin

  公开号：US20050222230A1

  公开（公告）日：2005-10-06

  The present invention pertains to the use of certain 3,4-diarylpyrazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar 3 is independently: a C 5-20 aryl group, and is optionally substituted; Ar 4 is independently: a C 5-20 aryl group, and is optionally substituted; R 5 is independently: hydrogen; halo; hydroxy; ether; formyl; acyl; carboxy; ester, acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamido; C 1-7 alkyl; C 3-20 heterocycyl; or C 5-20 aryl; RN is independently: —H; C 1-7 alkyl; C 3-20 heterocycyl; or, C 5-20 aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, such compounds for medical use, such compounds for use in the treatment of conditions mediated by HSP90, including, for example, cancer, and use of such compounds in the preparation of medicaments for such treatments.

  本发明涉及使用公式（I）中的某些3,4-二芳基吡唑化合物，无论是在体内还是体外，用于抑制热休克蛋白90（HSP90），以及用于治疗由HSP90介导的疾病，包括癌症等；其中：Ar3独立地表示：C5-20芳基基团，可选地取代；Ar4独立地表示：C5-20芳基基团，可选地取代；R5独立地表示：氢；卤素；羟基；醚；甲酰基；酰基；羧基；酯，酰氧基；氧羰酰氧基；酰胺；酰胺基；氨基羰酰氧基；四唑基；氨基；硝基；氰基；偶氮基；磺酰基；硫醚基；磺酰胺基；C1-7烷基；C3-20杂环基；或C5-20芳基；R N 独立地表示：-H；C1-7烷基；C3-20杂环基；或C5-20芳基；以及其药学上可接受的盐，溶剂化合物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及这种化合物，包含这种化合物的制药组合物，用于医学用途的这种化合物，用于治疗由HSP90介导的疾病，包括癌症的这种化合物，以及使用这种化合物制备这种治疗药物的用途。
• 3,4-DIARYLPYRAZOLES AND THEIR USE IN THE THERAPY OF CANCER
  申请人：Vernalis (Oxford) Ltd

  公开号：EP1456180A1

  公开（公告）日：2004-09-15
• 3-(2,4)DIHYDROXYPHENYL-4-PHENYLPYRAZOLES AND THEIR MEDICAL USE
  申请人：Vernalis (Cambridge) Limited

  公开号：EP1456180B1

  公开（公告）日：2007-10-03
• US7247734B2
  申请人：——

  公开号：US7247734B2

  公开（公告）日：2007-07-24