methyl 4-(phenethylcarbamoyl)butanoate | 242134-53-8

• 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 4-(phenethylcarbamoyl)butanoate
• 英文别名: Methyl 5-oxo-5-(2-phenylethylamino)pentanoate；methyl 5-oxo-5-(2-phenylethylamino)pentanoate
• CAS: 242134-53-8
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: SIXRTCXBUYYXAH-UHFFFAOYSA-N

物化性质

• 沸点：
  439.4±38.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(phenethylcarbamoyl)butanoate 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以90%的产率得到N¹-hydroxy-N⁵-phenethylglutaramide
  参考文献：
  名称：

  [EN] SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE
  [FR] COMPOSITIONS DE SANTACRUZAMATE A ET ANALOGUES ET PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2014018913A3
• 作为产物：
  描述：

  戊二酸单甲酯 、 2-苯乙胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到methyl 4-(phenethylcarbamoyl)butanoate
  参考文献：
  名称：

  Santacruzamate A, a Potent and Selective Histone Deacetylase Inhibitor from the Panamanian Marine Cyanobacterium cf. Symploca sp.

  摘要：

  A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a structurally intriguing hybrid molecule, which blends aspects of both agents (1 and 2), were achieved and evaluated for their HDAC activity and specificity.

  DOI：

  10.1021/np400198r

文献信息

• Marine Cytotoxin Santacruzamate A Derivatives as Potent HDAC1-3 Inhibitors and Their Synergistic Anti-Leukemia Effects with Venetoclax
  作者：Wanting Hao、Leyan Wang、Tongqiang Xu、Geng Jia、Yuqi Jiang、Chong Qin、Xiaoyang Li

  DOI：10.3390/md22060250

  日期：——

  Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.