4-azido-3-(S)-(2-(S)-{3-methyl-2-(S)-[(naphthalene-2-carbonyl)-amino]-butyrylamino}-propionylamino)-butyric acid | 912357-84-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 4-azido-3-(S)-(2-(S)-{3-methyl-2-(S)-[(naphthalene-2-carbonyl)-amino]-butyrylamino}-propionylamino)-butyric acid
• 英文别名: (3S)-4-azido-3-[[(2S)-2-[[(2S)-3-methyl-2-(naphthalene-2-carbonylamino)butanoyl]amino]propanoyl]amino]butanoic acid
• CAS: 912357-84-7
• 化学式: C₂₃H₂₈N₆O₅
• 分子量: 468.513
• InChiKey: WDMNRYZDTZMQOS-DCPHZVHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-azido-3-(S)-(2-(S)-{3-methyl-2-(S)-[(naphthalene-2-carbonyl)-amino]-butyrylamino}-propionylamino)-butyric acid 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 氨 、 N,N-二异丙基乙胺 作用下， 生成 4-azido-3-(S)-(2-(S)-{3-methyl-2-(S)-[(naphthalene-2-carbonyl)-amino]-butyrylamino}-propionylamino)-butyric acid amide
  参考文献：
  名称：

  Organic Azide Inhibitors of Cysteine Proteases

  摘要：

  Cysteine proteases are crucial regulatory enzymes in human physiology and disease. Inhibitors are usually designed with reactive electrophiles to covalently bond to the catalytic cysteinyl sulfur, and consequently they also indiscriminately interact with biological thiolates and other nucleophiles, leading to toxic side effects in vivo. Here we describe an alternative to using reactive electrophiles, demonstrating the use of a much less reactive azidomethylene substituent (-CH2-N3) that confers potent inhibition of cysteine proteases. This new approach resulted in potent, reversible, competitive inhibitors of caspase-1 (IC50 < 10 nM), with significant advantages over aldehydes such as high stability in vitro to thiols (10 mM dithiothreitol (pH 7.2), 20 mM glutathione (pH 7.2, 9, 11)) and aqueous media, as well as some highly desirable druglike features. It was also demonstrated that azides can be incorporated into inhibitors of other caspases (e.g. 3, 8) and cathepsins (e.g. K, S, B), indicating the versatility of this valuable new approach to cysteine protease inhibition.

  DOI：

  10.1021/ja0637649
• 作为产物：
  描述：

  在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 2.0h， 生成 4-azido-3-(S)-(2-(S)-{3-methyl-2-(S)-[(naphthalene-2-carbonyl)-amino]-butyrylamino}-propionylamino)-butyric acid
  参考文献：
  名称：

  WO2007/41775

  摘要：

  公开号：