3'-氟-4'-甲酰基-[1,1'-联苯]-4-腈 | 869767-75-9

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 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: 3'-氟-4'-甲酰基-[1,1'-联苯]-4-腈
• 英文名称: 3'-fluoro-4'-formylbiphenyl-4-carbonitrile
• 英文别名: 3'-fluoro-4'-formyl-[1,1'-biphenyl]-4-carbonitrile；4-(3-fluoro-4-formylphenyl)benzonitrile
• CAS: 869767-75-9
• 化学式: C₁₄H₈FNO
• 分子量: 225.222
• InChiKey: LDQOANSAUQUPKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3'-氟-4'-甲酰基-[1,1'-联苯]-4-腈 在 盐酸羟胺 、 potassium tert-butylate 、 sodium hydrogensulfite 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[3-fluoro-4'-(N-hydroxyamidino)biphenyl-4-yl]-1H-benzimidazole-5-(N-hydroxy)amidine
  参考文献：
  名称：

  Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents

  摘要：

  A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling reaction of the appropriate haloarylcarbonitriles la-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a-h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as judged by high Delta T-m values with poly(dA.dT)(2). The compounds were quite active in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3 to 37 nM. These compounds were even more active versus Plasmodium falciparum, exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate to good activity in vivo in the STIB900 model for acute African trypanosomiasis. The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.024
• 作为产物：
  描述：

  4-氰基苯硼酸 、 4-溴-2-氟苯甲醛 在 potassium carbonate 、 palladium dichloride 作用下， 以 水 为溶剂， 反应 3.0h， 以94%的产率得到3'-氟-4'-甲酰基-[1,1'-联苯]-4-腈
  参考文献：
  名称：

  基于手性羟基取代的联苯-二芳基嘧啶非核苷HIV-1逆转录酶抑制剂的基于生物立体异构的设计和对映体分析。

  摘要：

  七个羟基取代的联苯-二芳基嘧啶的单一对映体是通过生物立体异构策略设计和合成的，作为新型HIV-1非核苷逆转录酶抑制剂（NNRTIs）。细胞和酶促测定表明，新获得的化合物具有显着的活性和相对较低的细胞毒性。外消旋化合物的超临界流体色谱（SFC）对映体分离和对映体分析表明，（S）形式通常比（R）对应物更有效。在所有手性衍生物中，（S）-（-）- 12a在低纳摩尔浓度范围内，对野生型（WT）和单个突变菌株（L100I，K103N，Y181C，E138K；特别是Y188L）和RT酶具有最佳的抗病毒活性。对双重突变病毒株（F227L + V106A，RES056），（S）-（-）- 12a具有亚微摩尔抗病毒活性。此外，（S）-（-）- 12a显示出高的基于细胞的选择性指数（SI WT= 5822），并且在体内急性毒性试验和心电图中未观察到明显的毒性。分子对接研究预测了化合物与RT的结合模式，并解释了

  DOI：

  10.1016/j.ejmech.2020.112549

文献信息

• Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents
  作者：Mohamed A. Ismail、Adalgisa Batista-Parra、Yi Miao、W. David Wilson、Tanja Wenzler、Reto Brun、David W. Boykin

  DOI：10.1016/j.bmc.2005.07.024

  日期：2005.12

  A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling reaction of the appropriate haloarylcarbonitriles la-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a-h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as judged by high Delta T-m values with poly(dA.dT)(2). The compounds were quite active in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3 to 37 nM. These compounds were even more active versus Plasmodium falciparum, exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate to good activity in vivo in the STIB900 model for acute African trypanosomiasis. The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg. (c) 2005 Elsevier Ltd. All rights reserved.
• Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors
  作者：Xiaomei Chen、Li Ding、Yuan Tao、Christophe Pannecouque、Erik De Clercq、Chunlin Zhuang、Fen-Er Chen

  DOI：10.1016/j.ejmech.2020.112549

  日期：2020.9

  The single enantiomers of seven hydroxyl-substituted biphenyl-diarylpyrimidines were designed and synthesized by a bioisosterism strategy as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). The cellular and enzymatic assays indicated that the novel obtained compounds had significant activities and relatively low cytotoxicity. The supercritical fluid chromatography (SFC) enantioseparations

  七个羟基取代的联苯-二芳基嘧啶的单一对映体是通过生物立体异构策略设计和合成的，作为新型HIV-1非核苷逆转录酶抑制剂（NNRTIs）。细胞和酶促测定表明，新获得的化合物具有显着的活性和相对较低的细胞毒性。外消旋化合物的超临界流体色谱（SFC）对映体分离和对映体分析表明，（S）形式通常比（R）对应物更有效。在所有手性衍生物中，（S）-（-）- 12a在低纳摩尔浓度范围内，对野生型（WT）和单个突变菌株（L100I，K103N，Y181C，E138K；特别是Y188L）和RT酶具有最佳的抗病毒活性。对双重突变病毒株（F227L + V106A，RES056），（S）-（-）- 12a具有亚微摩尔抗病毒活性。此外，（S）-（-）- 12a显示出高的基于细胞的选择性指数（SI WT= 5822），并且在体内急性毒性试验和心电图中未观察到明显的毒性。分子对接研究预测了化合物与RT的结合模式，并解释了