ethyl [4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]acetate | 401518-15-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl [4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]acetate
• 英文别名: 2-(4-(3,4-dimethoxyphenyl)-4-cyanopiperidin-1-yl)acetic acid ethyl ester；Ethyl 4-cyano-4-(3,4-dimethoxyphenyl)-1-piperidineacetate；ethyl 2-[4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]acetate
• CAS: 401518-15-8
• 化学式: C₁₈H₂₄N₂O₄
• 分子量: 332.4
• InChiKey: SCFFGOMSEAJQEO-UHFFFAOYSA-N

物化性质

• 沸点：
  473.7±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl [4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]acetate 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.58h， 生成
  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：

  3,4-二甲氧基苯乙腈 在 茴香硫醚 、 potassium carbonate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl [4-cyano-4-(3,4-dimethoxyphenyl)piperidin-1-yl]acetate
  参考文献：
  名称：

  Highly potent PDE4 inhibitors with therapeutic potential

  摘要：

  Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo(TM) 1. Water-soluble piperidine derivatives were found to possess therapeutic potential. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.087

文献信息

• Piperidine derivatives and drugs containing these derivatives as active ingredient
  申请人：——

  公开号：US20040044036A1

  公开（公告）日：2004-03-04

  Piperidine derivatives represented by formula (I) or nontoxic salts thereof (wherein symbols are defined in the description): 1 Since the compound represented by formula (I) has a PDE4 inhibitory activity, it is useful for preventing and/or treating inflammatory diseases, diabetic diseases, allergic diseases, autoimmune diseases, osteoporosis, bone fracture, obesity, depression, Parkinson's disease, dementia, ischemia-reperfusion injury, leukemia and the like.

  Piperidine衍生物由公式(I)代表，或其无毒盐（其中符号在描述中定义）：由于公式(I)代表的化合物具有PDE4抑制活性，因此对于预防和/或治疗炎症性疾病、糖尿病、过敏性疾病、自身免疫疾病、骨质疏松症、骨折、肥胖症、抑郁症、帕金森病、痴呆症、缺血再灌注损伤、白血病等疾病是有用的。
• Piperidine derivatives and agent comprising the derivative as active ingredient
  申请人：Nakai Hisao

  公开号：US20060189656A1

  公开（公告）日：2006-08-24

  Piperidine derivatives represented by formula (I) or nontoxic salts thereof (wherein symbols are defined in the description): Since the compound represented by formula (I) has a PDE4 inhibitory activity, it is useful for preventing and/or treating inflammatory diseases, diabetic diseases, allergic diseases, autoimmune diseases, osteoporosis, bone fracture, obesity, depression, Parkinson's disease, dementia, ischemia-reperfusion injury, leukemia and the like.

  式(I)所代表的吡啶衍生物或其无毒盐（其中符号在描述中定义）：由于式(I)所代表的化合物具有PDE4抑制活性，因此对于预防和/或治疗炎症性疾病、糖尿病、过敏性疾病、自身免疫性疾病、骨质疏松症、骨折、肥胖症、抑郁症、帕金森病、痴呆症、缺血再灌注损伤、白血病等疾病具有用处。
• PIPERIDINE DERIVATIVES AND DRUGS CONTAINING THESE DERIVATIVES AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1308440B1

  公开（公告）日：2009-05-06
• US7109342B2
  申请人：——

  公开号：US7109342B2

  公开（公告）日：2006-09-19
• US7649095B2
  申请人：——

  公开号：US7649095B2

  公开（公告）日：2010-01-19