{4-cyano-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]piperidine-1-yl}acetic acid | 401518-45-4

• 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: {4-cyano-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]piperidine-1-yl}acetic acid
• 英文别名: 2-(4-(3-cyclopentyloxy-4-difluoromethoxyphenyl)-4-cyanopiperidin-1-yl)acetic acid；1-(2-Oxo-2-hydroxyethyl)-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]piperidine-4-carbonitrile；2-[4-cyano-4-[3-cyclopentyloxy-4-(difluoromethoxy)phenyl]piperidin-1-yl]acetic acid
• CAS: 401518-45-4
• 化学式: C₂₀H₂₄F₂N₂O₄
• 分子量: 394.418
• InChiKey: VSYNYAJTQPDCJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  82.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  {4-cyano-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]piperidine-1-yl}acetic acid 在 盐酸 、 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 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-{4-cyano-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]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：

  (3-cyclopentyloxy-4-difluoromethoxyphenyl) acetonitrile 在 sodium hydroxide 、 茴香硫醚 、 potassium carbonate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 {4-cyano-4-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]piperidine-1-yl}acetic acid
  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 derivative compounds and drugs containing the compounds as the active ingredient
  申请人：Ochiai Hiroshi

  公开号：US20050080107A1

  公开（公告）日：2005-04-14

  A piperidine derivative of formula (I) (wherein all symbols are as described in the specification.) and an intermediate for the preparation thereof. The compound of formula (I) has phosphodiesterase 4 inhibitory activity, and it is useful for the prevention and/or treatment of inflammatory diseases, diabetic diseases, allergic diseases, autoimmune diseases, ocular diseases, osteoporosis, bone fracture, osteoarthritis, obesity, bulimia, depression, Parkinson's disease, dementia, ischemia-reperfusion injury, leukemia, acquired immunodeficiency deficiency syndrome (AIDS), shock, systemically inflammatory responsive diseases (SIRS), etc.

  公式（I）的哌啶衍生物（其中所有符号如说明书所述）及其制备的中间体。公式（I）化合物具有磷酸二酯酶4抑制活性，可用于预防和/或治疗炎症性疾病，糖尿病性疾病，过敏性疾病，自身免疫性疾病，眼部疾病，骨质疏松症，骨折，骨关节炎，肥胖症，暴食症，抑郁症，帕金森病，痴呆症，缺血再灌注损伤，白血病，获得性免疫缺陷综合症（AIDS），休克，全身炎症反应性疾病（SIRS）等。
• 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。
• REMEDY FOR PRURITUS COMPRISING PIPERIDINE DERIVATIVE AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1647274A1

  公开（公告）日：2006-04-19

  It is intended to find out a novel pharmacological effect of a piperidine derivative (I). Because of having an excellent antipruritic effect, the piperidine derivative (1) is useful as a therapeutic agent for itching of any types such as eye itching, skin itching and systemic itching.

  本研究旨在发现一种哌啶衍生物（I）的新药理作用。由于哌啶衍生物（1）具有极佳的止痒效果，因此可用作任何类型瘙痒（如眼部瘙痒、皮肤瘙痒和全身瘙痒）的治疗剂。
• ｛４−シアノ−４−［３−（シクロペンチルオキシ）−４−（ジフルオロメトキシ）フェニル］ピペリジン−１−イル｝酢酸の結晶形
  申请人：小野薬品工業株式会社

  公开号：JP2007217349A

  公开（公告）日：2007-08-30

  【課題】本発明の目的は、医薬品として有用な｛４−シアノ−４−［３−（シクロペンチルオキシ）−４−（ジフルオロメトキシ）フェニル］ピペリジン−１−イル｝酢酸の保存安定性に優れた新規な結晶形を提供すること。【解決手段】 ｛４−シアノ−４−［３−（シクロペンチルオキシ）−４−（ジフルオロメトキシ）フェニル］ピペリジン−１−イル｝酢酸の新規な結晶形が、約２ヶ月保存後においても変化せず、優れた保存安定性を有するため、医薬品として有用である。【選択図】なし

  本发明的目的是提供一种药物有用的4-氰基-4-[3-(环戊基氧基)-4-(二氟甲氧基)苯基]哌啶-1-基}乙酸，它可作为药物产品，并提供新的晶体形式。(3-(环戊基氧基)-4-(二氟甲氧基)苯基]哌啶-1-基}乙酸，它是一种有用的医药产品，并提供一种具有优异储存稳定性的新晶形。解决方法] 4-氰基-4-[3-（环戊氧基）-4-（二氟甲氧基）苯基]哌啶4-氰基-4-[3-(环戊基氧基)-4-(二氟甲氧基)苯基]哌啶-1-基}乙酸的新晶型在贮存约 2 个月后仍保持不变，具有极佳的贮存稳定性，因此可用作医药产品。无。