toluene-4-sulfonic acid 3-azido-4-phenyl-2-(tetrahydropyran-2-yloxy)butyl ester | 1190630-73-9

• 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: toluene-4-sulfonic acid 3-azido-4-phenyl-2-(tetrahydropyran-2-yloxy)butyl ester
• 英文别名: [(2S,3S)-3-azido-2-(oxan-2-yloxy)-4-phenylbutyl] 4-methylbenzenesulfonate
• CAS: 1190630-73-9
• 化学式: C₂₂H₂₇N₃O₅S
• 分子量: 445.539
• InChiKey: FZDRUUGSVJCDEQ-UGGDCYSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  toluene-4-sulfonic acid 3-azido-4-phenyl-2-(tetrahydropyran-2-yloxy)butyl ester 在 palladium on activated charcoal 、 氢气 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 水 为溶剂， 反应 78.0h， 生成 (2R,3S)-3-Cbz-amino-2-hydroxy-4-phenyl-1-benzylaminobutane
  参考文献：
  名称：

  Nonpeptidic Lysosomal Modulators Derived from Z-Phe-Ala-Diazomethylketone for Treating Protein Accumulation Diseases

  摘要：

  Lysosomes are involved in protein turnover and removing misfolded species, and their enzymes have the potential to offset the defect in proteolytic clearance that contributes to the age-related dementia Alzheimer's disease (AD). The weak cathepsin B and L inhibitor Z-Phe-Ala-diazomethylketone (PADK) enhances lysosomal cathepsin levels at low concentrations, thereby eliciting protective clearance of PHF-tau and A beta 42 in the hippocampus and other brain regions. Here, a class of positive modulators is established with compounds decoupled from the cathepsin inhibitory properties. We utilized PADK as a departure point to develop nonpeptidic structures with the hydroxyethyl isostere. The first-in-class modulators SD1002 and SD1003 exhibit: : improved levels of cathepsin up-regulation but almost complete removal of cathepsin inhibitory properties as compared to PADK. Isomers of the lead compound SD1002 were synthesized, and the modulatory activity was determined to be stereoselective. In addition, the lead compound was tested in transgenic mice with results indicating protection against AD-type protein accumulation pathology.

  DOI：

  10.1021/ml300197h
• 作为产物：
  描述：

  (2S,3S)-2-azido-1-phenyl-butane-3,4-diol 在 4-甲基苯磺酸吡啶 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 toluene-4-sulfonic acid 3-azido-4-phenyl-2-(tetrahydropyran-2-yloxy)butyl ester
  参考文献：
  名称：

  Nonpeptidic Lysosomal Modulators Derived from Z-Phe-Ala-Diazomethylketone for Treating Protein Accumulation Diseases

  摘要：

  Lysosomes are involved in protein turnover and removing misfolded species, and their enzymes have the potential to offset the defect in proteolytic clearance that contributes to the age-related dementia Alzheimer's disease (AD). The weak cathepsin B and L inhibitor Z-Phe-Ala-diazomethylketone (PADK) enhances lysosomal cathepsin levels at low concentrations, thereby eliciting protective clearance of PHF-tau and A beta 42 in the hippocampus and other brain regions. Here, a class of positive modulators is established with compounds decoupled from the cathepsin inhibitory properties. We utilized PADK as a departure point to develop nonpeptidic structures with the hydroxyethyl isostere. The first-in-class modulators SD1002 and SD1003 exhibit: : improved levels of cathepsin up-regulation but almost complete removal of cathepsin inhibitory properties as compared to PADK. Isomers of the lead compound SD1002 were synthesized, and the modulatory activity was determined to be stereoselective. In addition, the lead compound was tested in transgenic mice with results indicating protection against AD-type protein accumulation pathology.

  DOI：

  10.1021/ml300197h

文献信息

• [EN] COMPOUNDS FOR LYSOSOMAL MODULATION AND METHODS OF USE<br/>[FR] COMPOSÉS POUR MODULATION LYSOSOMALE ET PROCÉDÉS D'UTILISATION
  申请人：UNIV CONNECTICUT

  公开号：WO2009129532A1

  公开（公告）日：2009-10-22

  Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by Aβ and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative diseases that involve protein accumulation and aggregation in the brain, such as Alzheimer's, Parkinson's and Huntington's Disease, are also provided.

  提供了用于促进溶酶体过程并从而改善由Aβ和其他蛋白质和糖蛋白物种引起的细胞和功能完整性破坏的化合物。还提供了用于治疗涉及蛋白质在大脑中积累和聚集的神经退行性疾病的方法，如阿尔茨海默病、帕金森病和亨廷顿病。
• MATERIALS FOR POSITIVE CATHEPSIN B MODULATION AND METHODS OF USE FOR TREATING MILD COGNITIVE IMPAIRMENT (MCI), EARLY DEMENTIA, A-SYNUCLEINOPATHY, TRAUMATIC BRAIN INJURY, CARDIOMYOPATHY, EYE DISEASE AND SKIN DAMAGE
  申请人：Bahr Ben A.

  公开号：US20160136229A1

  公开（公告）日：2016-05-19

  The present invention provides methods for treating a subject afflicted with i) Mild Cognitive Impairment (MCI), ii) early dementia, iii) early α-synucleinopathy, iv) traumatic brain injury, v) cardiomyopathy, vi) eye disease, or vii) skin damage, comprising administering to the subject at least one compound that increases the level of active cathepsin B in cells of the subject, or a pharmaceutically acceptable salt or ester thereof, in an amount that is effective to treat the subject. The present invention also provides compositions for treating a subject afflicted with i) Mild Cognitive Impairment (MCI), ii) early dementia, iii) early α-synucleinopathy, iv) traumatic brain injury, v) cardiomyopathy, vi) eye disease, or vii) skin damage.