[4-(4-phenoxybenzoyl)phenyl]acetonitrile | 876611-19-7

• 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: [4-(4-phenoxybenzoyl)phenyl]acetonitrile
• 英文别名: 2-[4-(4-Phenoxybenzoyl)phenyl]acetonitrile
• CAS: 876611-19-7
• 化学式: C₂₁H₁₅NO₂
• 分子量: 313.356
• InChiKey: DENLCSPARHKHSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [4-(4-phenoxybenzoyl)phenyl]acetonitrile 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以63%的产率得到[4-(4-phenoxybenzoyl)phenyl]acetic acid
  参考文献：
  名称：

  Novel 5α-Reductase Inhibitors:  Synthesis, Structure−Activity Studies, and Pharmacokinetic Profile of Phenoxybenzoylphenyl Acetic Acids

  摘要：

  Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5 alpha- reductase isozymes I and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC50 values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC50 = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm050728w
• 作为产物：
  描述：

  (4-methylphenyl)(4-phenoxyphenyl)methanone 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 1,4-二氧六环 、 四氯化碳 、 水 为溶剂， 反应 5.0h， 生成 [4-(4-phenoxybenzoyl)phenyl]acetonitrile
  参考文献：
  名称：

  Novel 5α-Reductase Inhibitors:  Synthesis, Structure−Activity Studies, and Pharmacokinetic Profile of Phenoxybenzoylphenyl Acetic Acids

  摘要：

  Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5 alpha- reductase isozymes I and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC50 values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC50 = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm050728w

文献信息

• Novel 5α-Reductase Inhibitors:  Synthesis, Structure−Activity Studies, and Pharmacokinetic Profile of Phenoxybenzoylphenyl Acetic Acids
  作者：Ola I. A. Salem、Martin Frotscher、Christiane Scherer、Alexander Neugebauer、Klaus Biemel、Martina Streiber、Ruth Maas、Rolf W. Hartmann

  DOI：10.1021/jm050728w

  日期：2006.1.1

  Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5 alpha- reductase isozymes I and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC50 values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC50 = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.