1-(3-benzyloxy-4-methoxyphenyl)cyclopen-3-ene-1-carbonitrile | 763109-95-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(3-benzyloxy-4-methoxyphenyl)cyclopen-3-ene-1-carbonitrile
• 英文别名: 1-(4-methoxy-3-phenylmethoxyphenyl)cyclopent-3-ene-1-carbonitrile
• CAS: 763109-95-1
• 化学式: C₂₀H₁₉NO₂
• 分子量: 305.376
• InChiKey: ZKHSTPHQJZOBQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  457.3±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.39
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42.25
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(3-benzyloxy-4-methoxyphenyl)cyclopen-3-ene-1-carbonitrile 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 臭氧 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 7.42h， 生成 ethyl [4-cyano-4-(3-hydroxy-4-methoxyphenyl)piperidin-1-yl]acetate
  参考文献：
  名称：

  Highly potent PDE4 inhibitors with therapeutic potential

  摘要：

  The hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system prompted us to design and synthesize a hydrophilic piperidine analog to improve the side effect profile of Ariflo(TM) 1, which is an orally active second-generation PDE4 inhibitor. During evaluation of various water-soluble piperidine analogs, 2a-b, 11b-14b, and 17a showed therapeutic potential in cross-species comparison studies. The following three findings were obtained: (1) The hydroxamic acid group, a well known metal chelator, caused a marked increase of inhibitory activity. (2) Water-soluble piperidine analogs lacked the configurational isomerism of Ariflo 1 without loss of inhibitory activity. (3) Replacement of the 4-methoxy residue with a difluoromethoxy residue led to an increase of in vivo potency. Structure-activity relationships are presented. Single-dose rat pharmacokinetic data for 11b, 12b, and 17a are also presented. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.032
• 作为产物：
  描述：

  顺式-1,4-二氯-2-丁烯 、 (3-苄氧基-4-甲氧基苯基)-乙腈 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以93%的产率得到1-(3-benzyloxy-4-methoxyphenyl)cyclopen-3-ene-1-carbonitrile
  参考文献：
  名称：

  Highly potent PDE4 inhibitors with therapeutic potential

  摘要：

  The hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system prompted us to design and synthesize a hydrophilic piperidine analog to improve the side effect profile of Ariflo(TM) 1, which is an orally active second-generation PDE4 inhibitor. During evaluation of various water-soluble piperidine analogs, 2a-b, 11b-14b, and 17a showed therapeutic potential in cross-species comparison studies. The following three findings were obtained: (1) The hydroxamic acid group, a well known metal chelator, caused a marked increase of inhibitory activity. (2) Water-soluble piperidine analogs lacked the configurational isomerism of Ariflo 1 without loss of inhibitory activity. (3) Replacement of the 4-methoxy residue with a difluoromethoxy residue led to an increase of in vivo potency. Structure-activity relationships are presented. Single-dose rat pharmacokinetic data for 11b, 12b, and 17a are also presented. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.032