santacruzamate A | 1477949-42-0

• 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: santacruzamate A
• 英文别名: Cay10683；ethyl 3-(phenethylcarbamoyl)propylcarbamate；Santacruzamate A；ethyl N-[4-oxo-4-(2-phenylethylamino)butyl]carbamate
• CAS: 1477949-42-0
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: HTOYBIILVCHURC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  -20℃

制备方法与用途

Santa Cruz Amate A 是一类天然产物，是一种高效且具选择性的组蛋白去乙酰化酶抑制剂。

反应信息

• 作为产物：
  描述：

  4-(乙氧基羰基氨基)丁酸 、 2-苯乙胺 在 N-甲基吗啉 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 四氢呋喃 为溶剂， 反应 14.25h， 以70%的产率得到santacruzamate A
  参考文献：
  名称：

  基于圣克鲁斯酸酯-A的类似物的合成和生物学评估

  摘要：

  合成了Santacruzamate-A（一种与SAHA结构相关的天然产物）的几种衍生物，以探索氨基甲酸酯和草酰酰胺作为靶向锌依赖性组蛋白脱乙酰基酶（HDAC）催化位点的新型偏向元件的潜力。合成了另一类Santacruzamate-A衍生物，以研究帽基和连接子元素对HDAC抑制活性的影响。在HCT116细胞中的MTT分析中，对所有化合物的体外细胞毒性活性进行剂量反应评估。通过蛋白质印迹分析在体外评估HDAC抑制活性，以进行组蛋白超乙酰化分析，并通过生化方法评估代表性的人HDAC同工型。鉴定出两种新颖的化合物表现出有效的时间依赖性抗增殖活性。然而，与异羟肟酸类似物不同，所测试的Santacruzamate-A衍生物没有明显的HDAC抑制活性。氨基甲酸乙酯部分作为不常见的锌结合基团，不具有协调锌离子的能力，因此，推测不能与HDAC催化位点重现已知的抑制剂-底物锌结合基团的相互作用。这项研究证实，

  DOI：

  10.1016/j.bmc.2017.10.026

文献信息

• Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents
  作者：Qi Liu、Wenhua Lu、Mingzhe Ma、Jianwei Liao、A. Ganesan、Yumin Hu、Shijun Wen、Peng Huang

  DOI：10.1039/c4ra13889a

  日期：——

  Santacruzamate A, a recently discovered natural product from a Panamanian marine cyanobacterium Symploca sp., features a similar structure to the clinically used histone deacetylase (HDAC) inhibitor vorinostat (SAHA). We have synthesized the natural product and a small set of analogues for SAR studies. To our surprise, the synthetic natural product santacruzamate A (1a) and the analogues did not show

  SAntacruzamate A是巴拿马海洋蓝藻Symploca sp。最近发现的天然产物，其结构与临床使用的组蛋白脱乙酰基酶（HDAC）抑制剂伏立诺他（vorastat）（SAHA）类似。我们已经合成了天然产物和少量类似物用于SAR研究。令我们惊讶的是，在HDAC酶测定中，合成的天然产物圣克鲁斯酸酯A（1a）及其类似物即使在2μM时也没有表现出明显的抑制作用，而原始报告中的IC 50值为0.12 nM。然而，发现一种含有末端硫脲基序的新型化合物5可以抑制亚微摩尔浓度的恶性细胞的生长。而且5CCD841对正常人结肠上皮细胞CCD841没有细胞毒性，表明其细胞毒性对癌细胞具有特异性。进一步的研究表明，该化合物诱导细胞凋亡，影响细胞周期进程并增加ROS的产生。我们认为其作用机理与HDAC抑制无关，因此报告中有关甜菊酸酯的原始活性需要重新评估。
• [EN] SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE<br/>[FR] COMPOSITIONS DE SANTACRUZAMATE A ET ANALOGUES ET PROCÉDÉS D'UTILISATION
  申请人：UNIV CONNECTICUT

  公开号：WO2014018913A3

  公开（公告）日：2014-07-03
• Santacruzamate A, a Potent and Selective Histone Deacetylase Inhibitor from the Panamanian Marine Cyanobacterium cf. <i>Symploca</i> sp.
  作者：Christopher M. Pavlik、Christina Y. B. Wong、Sophia Ononye、Dioxelis D. Lopez、Niclas Engene、Kerry L. McPhail、William H. Gerwick、Marcy J. Balunas

  DOI：10.1021/np400198r

  日期：2013.11.22

  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.
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.