{1-[(1,3-thiazol-2-ylthio)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate | 787604-45-9

• 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-[(1,3-thiazol-2-ylthio)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate
• 英文别名: [1-(1,3-thiazol-2-ylsulfanylmethyl)cyclobutyl]methyl N-[(3S)-2-hydroxy-1-oxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate
• CAS: 787604-45-9
• 化学式: C₂₅H₃₅N₃O₄S₂
• 分子量: 505.703
• InChiKey: HYAOLZAUVPQHQO-LGWYJFNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  {1-[(1,3-thiazol-2-ylthio)methyl]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-(1,3-thiazol-2-ylsulfanylmethyl)cyclobutyl]methyl N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate
  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 、 偶氮二甲酸二叔丁酯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 27.08h， 生成 {1-[(1,3-thiazol-2-ylthio)methyl]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

• 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.