{1-[(benzyloxy)methyl]cyclobutyl}acetonitrile | 568591-41-3

• 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: {1-[(benzyloxy)methyl]cyclobutyl}acetonitrile
• 英文别名: 2-[1-(phenylmethoxymethyl)cyclobutyl]acetonitrile
• CAS: 568591-41-3
• 化学式: C₁₄H₁₇NO
• 分子量: 215.295
• InChiKey: OOVYHFBBEYCNSS-UHFFFAOYSA-N

物化性质

• 沸点：
  344.1±15.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  {1-[(benzyloxy)methyl]cyclobutyl}acetonitrile 在 二硫代磷酸二乙酯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以71%的产率得到2-{1-[(benzyloxy)methyl]cyclobutyl}ethanethioamide
  参考文献：
  名称：

  Ketoamide-Based Inhibitors of Cysteine Protease, Cathepsin K:  P3 Modifications

  摘要：

  Osteoporosis is a disease characterized by skeletal fragility. Cathepsin K, a lysosomal cysteine protease, has been implicated in the osteoclast mediated bone resorption. Inhibitors of this protease could potentially treat this skeletal disease. The present work describes exploration of the spatial requirements of the S3 subsite by the use of various sterically demanding P3 substituents. Sulfur and oxygen linked heterocycles as well as those without heteroatom linkers were found to provide potent inhibitors of cathepsin K. Representative examples from these series also afforded quite good selectivity ratios against most cathepsins tested. The tolerability of the S3 subsite for sterically demanding groups that provide potency and selectivity enhances the attractiveness of P3 changes to improve the physiochemical properties of inhibitors in the developments of compounds for the treatment of osteoporosis.

  DOI：

  10.1021/jm040107n
• 作为产物：
  描述：

  1,1-环丁烷-乙二酸二乙酯 在 lithium aluminium tetrahydride 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 {1-[(benzyloxy)methyl]cyclobutyl}acetonitrile
  参考文献：
  名称：

  Ketoamide-Based Inhibitors of Cysteine Protease, Cathepsin K:  P3 Modifications

  摘要：

  Osteoporosis is a disease characterized by skeletal fragility. Cathepsin K, a lysosomal cysteine protease, has been implicated in the osteoclast mediated bone resorption. Inhibitors of this protease could potentially treat this skeletal disease. The present work describes exploration of the spatial requirements of the S3 subsite by the use of various sterically demanding P3 substituents. Sulfur and oxygen linked heterocycles as well as those without heteroatom linkers were found to provide potent inhibitors of cathepsin K. Representative examples from these series also afforded quite good selectivity ratios against most cathepsins tested. The tolerability of the S3 subsite for sterically demanding groups that provide potency and selectivity enhances the attractiveness of P3 changes to improve the physiochemical properties of inhibitors in the developments of compounds for the treatment of osteoporosis.

  DOI：

  10.1021/jm040107n

文献信息

• Cycloalkyl ketoamides derivatives useful as cathepsin k inhibitors
  申请人：Catalano George John

  公开号：US20050054819A1

  公开（公告）日：2005-03-10

  Cycloalkyl ketoamide derivatives, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such cycloalkyl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文介绍了环状酰胺类酮衍生物，其作为卡他普星K抑制剂具有用途。所述发明还包括制备这种环状酰胺类酮衍生物的方法，以及使用它们治疗与增强骨转换相关的疾病（包括骨质疏松症），最终可导致骨折的方法。
• CYCLOALKYL KETOAMIDES DERIVATIVES USEFUL AS CATHEPSIN K INHIBITORS
  申请人：Catalano George John

  公开号：US20080058333A1

  公开（公告）日：2008-03-06

  Cycloalkyl ketoamide derivatives, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such cycloalkyl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文描述了环状烷基酮酰胺衍生物，其作为猫hepsin K抑制剂具有用途。所述发明还包括制备这种环状烷基酮酰胺衍生物的方法，以及使用它们治疗与增强骨转换相关的疾病的方法，包括骨质疏松症，最终可能导致骨折。
• Cycloalkyl ketoamides derivatives useful as cathepsin K inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US07282512B2

  公开（公告）日：2007-10-16

  Cycloalkyl ketoamide derivatives, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such cycloalkyl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文描述了用作cathepsin K抑制剂的环状酰胺衍生物。所述的发明还包括制备这种环状酰胺衍生物的方法，以及在治疗与增强骨转换有关的疾病，包括骨质疏松症，最终可能导致骨折的方法。
• US7282512B2
  申请人：——

  公开号：US7282512B2

  公开（公告）日：2007-10-16
• [EN] CYCLOALKYL KETOAMIDES DERIVATIVES USEFUL AS CATHEPSIN K INHIBITORS<br/>[FR] DERIVES DE CETOAMIDES A SUBSTITUTION CYCLOALKYLE, UTILES COMME INHIBITEURS DE CATHEPSINE K
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003062192A1

  公开（公告）日：2003-07-31

  Cycloalkyl ketoamide derivatives, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such cycloalkyl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.