L-valinyl-L-aspartyl-β-(tert-butyl ester) methyl ester | 77284-99-2

• 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: L-valinyl-L-aspartyl-β-(tert-butyl ester) methyl ester
• 英文别名: L-valyl-L-aspartyl-β-(tert-butyl ester) methyl ester；N-(valinyl)aspartic acid β-tert-butyl α-methyl ester；4-O-tert-butyl 1-O-methyl (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]butanedioate
• CAS: 77284-99-2
• 化学式: C₁₄H₂₆N₂O₅
• 分子量: 302.371
• InChiKey: CKSGSZCPRHGNID-ONGXEEELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-valinyl-L-aspartyl-β-(tert-butyl ester) methyl ester 在 N-甲基吗啉 、 potassium fluoride 、 lithium hydroxide 、 氢溴酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.83h， 生成 (S)-3-{(S)-3-Methyl-2-[2-(naphthalen-1-yloxy)-acetylamino]-butyrylamino}-4-oxo-5-(quinolin-8-yloxy)-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Structure–activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads

  摘要：

  Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.036
• 作为产物：
  描述：

  Z-VD(tBu)-OMe 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 L-valinyl-L-aspartyl-β-(tert-butyl ester) methyl ester
  参考文献：
  名称：

  (Substituted)acyl dipeptidyl inhibitors of the ICE/ced-3 family of cysteine proteases

  摘要：

  这项发明涉及新型（取代）酰基二肽酶ICE/ced-3家族抑制剂化合物。该发明还涉及含有这些化合物的药物组合物，以及将这些组合物用于治疗患有炎症、自身免疫和神经退行性疾病的患者，预防缺血性损伤，并保护即将进行移植手术的器官。

  公开号：

  US20030232788A1

文献信息

• Structure–Activity relationships within a series of caspase inhibitors: effect of leaving group modifications
  作者：Brett R. Ullman、Teresa Aja、Thomas L. Deckwerth、Jose-Luis Diaz、Julia Herrmann、Vincent J. Kalish、Donald S. Karanewsky、Steven P. Meduna、Kip Nalley、Edward D. Robinson、Silvio P. Roggo、Robert O. Sayers、Albert Schmitz、Robert J. Ternansky、Kevin J. Tomaselli、Joe C. Wu

  DOI：10.1016/s0960-894x(03)00755-8

  日期：2003.10

  Various aryloxy methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A systematic study of their structure-activity relationship (SAR) related to caspases 1, 3, 6, and 8 is reported. Highly potent irreversible broad-spectrum caspase inhibitors have been identified. Their efficacy in cellular models of cell death and inflammation are also discussed. (C) 2003 Elsevier Ltd. All rights reserved.
• US7157430B2
  申请人：——

  公开号：US7157430B2

  公开（公告）日：2007-01-02
• (Substituted)acyl dipeptidyl inhibitors of the ICE/ced-3 family of cysteine proteases
  申请人：Idun Pharmaceuticals, Inc.

  公开号：US20030232788A1

  公开（公告）日：2003-12-18

  This invention is directed to novel (substituted)acyl dipeptidyl ICE/ced-3 family inhibitor compounds. The invention is also directed to pharmaceutical compositions containing these compounds, as well as the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, for the prevention of ischemic injury, and for the preservation of organs that are to undergo a transplantation procedure.

  这项发明涉及新型（取代）酰基二肽酶ICE/ced-3家族抑制剂化合物。该发明还涉及含有这些化合物的药物组合物，以及将这些组合物用于治疗患有炎症、自身免疫和神经退行性疾病的患者，预防缺血性损伤，并保护即将进行移植手术的器官。
• Structure–activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads
  作者：Brett R. Ullman、Teresa Aja、Ning Chen、Jose-Luis Diaz、Xin Gu、Julia Herrmann、Vincent J. Kalish、Donald S. Karanewsky、Lalitha Kodandapani、Joseph J. Krebs、Steven D. Linton、Steven P. Meduna、Kip Nalley、Edward D. Robinson、Silvio P. Roggo、Robert O. Sayers、Albert Schmitz、Robert J. Ternansky、Kevin J. Tomaselli、Joe C. Wu

  DOI：10.1016/j.bmcl.2005.05.036

  日期：2005.8

  Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified. (c) 2005 Elsevier Ltd. All rights reserved.