tert-butyl 4-cyano-4-(3,4-dimethoxyphenyl)piperidine-1-carboxylate | 666179-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-cyano-4-(3,4-dimethoxyphenyl)piperidine-1-carboxylate
• 英文别名: 1-Boc-4-cyano-4-(3,4-dimethoxyphenyl)-piperidine
• CAS: 666179-93-7
• 化学式: C₁₉H₂₆N₂O₄
• 分子量: 346.426
• InChiKey: LAWWVLUAUGYBSD-UHFFFAOYSA-N

物化性质

• 沸点：
  483.2±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-cyano-4-(3,4-dimethoxyphenyl)piperidine-1-carboxylate 在 盐酸 、 sodium hydroxide 、 茴香硫醚 、 potassium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.58h， 生成 2-[4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]-N-hydroxyacetamide hydrochloride
  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：

  N-叔丁氧羰基二乙胺 在 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.17h， 生成 tert-butyl 4-cyano-4-(3,4-dimethoxyphenyl)piperidine-1-carboxylate
  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

文献信息

• Highly potent PDE4 inhibitors with therapeutic potential
  作者：Hiroshi Ochiai、Tazumi Ohtani、Akiharu Ishida、Kensuke Kusumi、Masashi Kato、Hiroshi Kohno、Yoshihiko Odagaki、Katuya Kishikawa、Susumu Yamamoto、Hiroshi Takeda、Takaaki Obata、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2004.06.032

  日期：2004.9

  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.