3-benzyloxy-4-difluoromethoxyphenylacetonitrile | 577968-61-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-benzyloxy-4-difluoromethoxyphenylacetonitrile
• 英文别名: 2-[4-(Difluoromethoxy)-3-phenylmethoxyphenyl]acetonitrile
• CAS: 577968-61-7
• 化学式: C₁₆H₁₃F₂NO₂
• 分子量: 289.282
• InChiKey: UZTFGEJDHRNJIE-UHFFFAOYSA-N

物化性质

• 沸点：
  406.8±40.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-benzyloxy-4-difluoromethoxyphenylacetonitrile 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 臭氧 、 溶剂黄146 、 三苯基膦 、 lithium hexamethyldisilazane 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 24.92h， 生成 methyl {4-cyano-4-[4-(difluoromethoxy)-3-(2,3-dihydro-1H-inden-2-yloxy)phenyl]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：

  4-二氟甲氧基-3-羟基苯甲醛 在 甲醇 、 sodium tetrahydroborate 、 potassium carbonate 、 sodium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 3-benzyloxy-4-difluoromethoxyphenylacetonitrile
  参考文献：
  名称：

  一种新型哌啶衍生物及其药物用途

  摘要：

  本公开涉及一种新型哌啶衍生物及其药物用途。具体而言，提供式I所示化合物或其可药用盐或其立体异构体、旋转异构体或互变异构体或氘代物，该类化合物具有PDE4B1或PDE4D3抑制活性，可用于治疗或预防与PDE4相关疾病，如炎症性疾病、糖尿病或变应性疾病，式I各基团定义与说明中一致。

  公开号：

  CN113121417A

文献信息

• 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 DERIVATIVE COMPOUNDS AND DRUGS CONTAINING THE COMPOUNDS AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1481969B1

  公开（公告）日：2011-01-19
• US7425567B2
  申请人：——

  公开号：US7425567B2

  公开（公告）日：2008-09-16
• 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.
• 一种新型哌啶衍生物及其药物用途
  申请人：苏州盛迪亚生物医药有限公司

  公开号：CN113121417A

  公开（公告）日：2021-07-16

  本公开涉及一种新型哌啶衍生物及其药物用途。具体而言，提供式I所示化合物或其可药用盐或其立体异构体、旋转异构体或互变异构体或氘代物，该类化合物具有PDE4B1或PDE4D3抑制活性，可用于治疗或预防与PDE4相关疾病，如炎症性疾病、糖尿病或变应性疾病，式I各基团定义与说明中一致。