| 1121703-11-4

• 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
• CAS: 1121703-11-4
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: HFHOQIVCMVZDBT-ZENAZSQFSA-N

物化性质

• 沸点：
  595.0±50.0 °C(predicted)
• 密度：
  1.169±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.28
• 重原子数：
  24.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84.58
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  在 1-羟基苯并三唑 、 sodium thiosulfate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S,E)-N-benzyl-3-(3-(3,4-bis(methoxymethoxy)phenyl)acrylamido)-2-oxo-4-phenylbutanamide
  参考文献：
  名称：

  作为抗利什曼病药物的迷迭香酸-β-氨基-α-酮酰胺杂化物的设计、合成和再利用

  摘要：

  合成了一系列迷迭香酸-β-氨基-α-酮酰胺杂化物，并合理地重新用于鉴定新的抗利什曼尼命中化合物。两种杂交体 2g 和 2h 显示出良好的活性（针对杜氏利什曼原虫前鞭毛体的 IC50 值分别为 9.5 和 8.8 μM）。它们的活性与 erufosine 相当。此外，使用人THP-1细胞的细胞毒性评估显示，两种杂交体2g和2h在高达100μM时不具有细胞毒性作用，而erufosine具有细胞毒性，CC50值为19.4μM。计算机对接提供了对结构-活性关系的见解，强调了肉桂酰基羰基的 α-碳上的脂肪链的重要性，在杂种 2g 和 2h 中与 LdCALP 和 LARG 建立了有利的结合相互作用。根据这些发现，杂种 2g 和 2h 被建议作为潜在安全的抗利什曼病化合物，用于进一步开发抗利什曼病药物。

  DOI：

  10.3390/ph16111594

文献信息

• Design and synthesis of 4-aryl-4-oxobutanoic acid amides as calpain inhibitors
  作者：Yong Zhang、Seo Yoon Jung、Changbae Jin、Nam Doo Kim、Ping Gong、Yong Sup Lee

  DOI：10.1016/j.bmcl.2008.11.030

  日期：2009.1

  The involvement of mu-calpain in neurological disorders, such as stroke and Alzheimer's disease has attracted considerable interest in the use of calpain inhibitors as therapeutic agents. 4-Aryl-4-oxobutanoic acid amide derivatives 4 were designed as acyclic variants of mu-calpain inhibitory chromone and quinolinone derivatives. Of the compounds synthesized, 4c-2, which possesses a 2-methoxymethoxy group at the phenyl ring and a primary amide at the warhead region most potently inhibited mu-calpain (IC50 = 0.34 mu M). Our findings suggest that the 4-aryl-4-oxobutanoic acid amide derivatives should be considered as a new family of mu-calpain inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
• Design and synthesis of calpain inhibitory 6-pyridone 2-carboxamide derivatives
  作者：Ki Yong Lee、Kwang Seob Lee、Changbae Jin、Yong Sup Lee

  DOI：10.1016/j.ejmech.2008.02.023

  日期：2009.3

  Excessive calpain activation contributes to serious cellular damage in many pathological conditions. The involvement of mu-calpain in neurological disorders such as, stroke and Alzheimer's disease has attracted considerable interest in the use of calpain inhibitors as therapeutic agents. 6-Pyridone 2-carboxamides derived from ketoamides were synthesized as conformationally constrained structures resembling the well known peptidic mu-calpain inhibitor, MDL 28,170, and their mu-calpain inhibitory activities were evaluated. Of the compounds synthesized, compound 2a, which has a primary amide at warhead region of the inhibitor most potently inhibited mu-calpain with an IC50 value of 2.81 +/- 1.26 mu M, which is ca. 40-fold less than that of MDL 28,170. (C) 2008 Elsevier Masson SAS. All rights reserved.