(1-{3-[(1-methyl-1H-imidazol-2-yl)sulfanyl]propyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate | 568591-89-9

• 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: (1-{3-[(1-methyl-1H-imidazol-2-yl)sulfanyl]propyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate
• 英文别名: [1-[3-(1-methylimidazol-2-yl)sulfanylpropyl]cyclobutyl]methyl N-[(3S)-2-hydroxy-1-oxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate
• CAS: 568591-89-9
• 化学式: C₂₈H₄₂N₄O₄S
• 分子量: 530.732
• InChiKey: NAMYVGVEZNVELA-RZVHPXSESA-N

物化性质

• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1-{3-[(1-methyl-1H-imidazol-2-yl)sulfanyl]propyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate 在 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 [1-(1-Phenyl-ethylaminooxalyl)-pentyl]-carbamic acid 1-[3-(1-methyl-1H-imidazol-2-ylsulfanyl)-propyl]-cyclobutylmethyl ester
  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：

  环丁烷甲酸乙酯 在 palladium on activated charcoal 咪唑 、 lithium aluminium tetrahydride 、 偶氮二甲酸二叔丁酯 、 四丁基氟化铵 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 90.33h， 生成 (1-{3-[(1-methyl-1H-imidazol-2-yl)sulfanyl]propyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate
  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：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。
• US7282512B2
  申请人：——

  公开号：US7282512B2

  公开（公告）日：2007-10-16
• Ketoamide-Based Inhibitors of Cysteine Protease, Cathepsin K:  P3 Modifications
  作者：Francis X. Tavares、David N. Deaton、Larry R. Miller、Lois L. Wright

  DOI：10.1021/jm040107n

  日期：2004.10.1

  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.