benzyl 1-{4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl}cyclopropanecarboxylate | 401518-89-6

• 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: benzyl 1-{4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl}cyclopropanecarboxylate
• 英文别名: 1-(4-(3-cyclopropylmethoxy-4-methoxyphenyl)-4-cyanopiperidin-1-yl)cyclopropanecarboxylic acid benzyl ester；Benzyl 1-[4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl]cyclopropane-1-carboxylate
• CAS: 401518-89-6
• 化学式: C₂₈H₃₂N₂O₄
• 分子量: 460.573
• InChiKey: XLBVNEPXGPKDAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  benzyl 1-{4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl}cyclopropanecarboxylate 在 palladium on activated charcoal 盐酸 、 氢气 、 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 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 1-{4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl}-N-hydroxycyclopropanecarboxamide 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：

  1-(3-methoxymethoxy-4-methoxyphenyl)cyclopen-3-ene-1-carbonitrile 在 盐酸 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 臭氧 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.92h， 生成 benzyl 1-{4-cyano-4-[3-(cyclopropylmethoxy)-4-methoxyphenyl]piperidin-1-yl}cyclopropanecarboxylate
  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

• 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