methyl (2S,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate | 134359-72-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (2S,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate
• 英文别名: methyl (2R,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate；methyl (2RS,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate
• CAS: 134359-72-1；134359-91-4
• 化学式: C₁₂H₂₃NO₅
• 分子量: 261.318
• InChiKey: CDZJKNXJNNQMDW-IENPIDJESA-N

物化性质

• 沸点：
  377.8±32.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.07
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl (2S,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma

  摘要：

  Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.

  DOI：

  10.1021/jm501102h
• 作为产物：
  描述：

  ((S)-2-cyano-2-hydroxy-1-isopropylethyl)carbamic acid benzyl ester 在 盐酸 、 水 、 苯甲醚 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 反应 39.0h， 生成 methyl (2S,3S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-methylpentanoate
  参考文献：
  名称：

  The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma

  摘要：

  Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.

  DOI：

  10.1021/jm501102h

文献信息

• Synthesis and biological activity of angiotensin II analog containing a Val-His replacement, Val.psi.[CH(CONH2)HN]His
  作者：Raju Mohan、Yuo Ling Chou、Ron Bihovsky、William C. Lumma、Paul W. Erhardt、Kenneth J. Shaw

  DOI：10.1021/jm00112a014

  日期：1991.8

  The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea

  将二肽模拟物Val psi [CH（CONH2）NH] His（4）掺入血管紧张素II（AII）类似物中，以提供八肽aralasin衍生物（29）以及四肽类似物19。三个C端四肽（21，25 （和28）也已准备好。测试了所有化合物从兔肾上腺匀浆中置换3H-AII的能力以及在豚鼠回肠上作为AII和AI的拮抗剂的能力。八肽类似物29的活性比亲本肽30低700倍。所有C末端片段19、21、25和28均没有可测量的AII拮抗剂活性。在四个四肽片段中，只有21个显示出任何明显的结合活性。
• Total synthesis of Myxoprincomide, a secondary metabolite from <i>Myxococcus xanthus</i>
  作者：Michael Kohr、Christine Walt、Jan Dastbaz、Rolf Müller、Uli Kazmaier

  DOI：10.1039/d2ob02021a

  日期：——

  Myxoprincomide, a secondary metabolite of the myxobacterium Myxococcus xanthus DK 1622, is synthesised for the first time. The central, unusual α-ketoamide is generated at the end of the synthesis to avoid side reactions during the synthesis of this rather reactive subunit. Nevertheless, the synthetic natural product is obtained as an isomeric mixture. Detailed analytical investigations show that the

  Myxoprincomide 是粘杆菌 Myxococcus xanthus DK 1622 的次级代谢产物，首次合成。中心的、不寻常的 α-酮酰胺是在合成结束时产生的，以避免在合成这种相当活泼的亚基过程中发生副反应。然而，合成天然产物是作为异构混合物获得的。详细的分析研究表明，在分离的天然产物中发现了相同的异构体混合物。