7-trityloxycarbamoyl-heptanoic acid methyl ester | 449729-22-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 7-trityloxycarbamoyl-heptanoic acid methyl ester
• 英文别名: Methyl 8-oxo-8-(trityloxyamino)octanoate
• CAS: 449729-22-0
• 化学式: C₂₈H₃₁NO₄
• 分子量: 445.558
• InChiKey: WPDFCFKPRHNGPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-trityloxycarbamoyl-heptanoic acid methyl ester 在 N-甲基吗啉 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 生成 (S)-3-(4-nitro-phenyl)-2-(7-trityloxycarbamoyl-heptanoylamino)propionic acid methyl ester
  参考文献：
  名称：

  Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells

  摘要：

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.

  DOI：

  10.1021/jm0208119
• 作为产物：
  描述：

  2-[三(苯基)甲氧基]异吲哚-1,3-二酮 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 氯仿 为溶剂， 反应 0.5h， 生成 7-trityloxycarbamoyl-heptanoic acid methyl ester
  参考文献：
  名称：

  结构多样的组蛋白脱乙酰酶光反应探针：活细胞和组织中的设计、合成和光标记研究。

  摘要：

  通过翻译后修饰和多蛋白复合物的形成在体内调节组蛋白脱乙酰酶 (HDAC) 活性。需要新的化学工具来研究这些因素如何影响细胞和组织中 HDAC 抑制剂 (HDACi) 对 HDAC 亚型的参与。在这项研究中，开发了一种获取化学多样性光反应探针 (PRP) 的合成策略，并用于制备七种新型 HDAC PRP 9-15。在活 SET-2、HepG2、HuH7 和 HEK293T 细胞系以及小鼠肝组织中的生化分析和光标记实验中确定了 PRP 与 I 类 HDAC 亚型的结合。与针对重组 HDAC 的 HDAC 蛋白丰度和生化活性不同，PRP 的化学型和细胞类型是定义 HDAC 同种型在活细胞中的参与的关键。

  DOI：

  10.1002/cmdc.201900114

文献信息

• Oxidation/Alkylation of Amino Acids with α-Bromo Carbonyls Catalyzed by Copper and Quick Access to HDAC Inhibitor
  作者：Yuqiong Tan、Huan Xiang、Jiayan Jin、Xingrui He、Shijun Li、Yang Ye

  DOI：10.1021/acs.joc.3c02218

  日期：2023.12.15

  A facile and efficient method was reported for Cu-catalyzed selective α-alkylation processes of amino acids/peptides and α-bromo esters/ketones through a radical–radical coupling pathway. The reaction displays an excellent functional group tolerance and broad substrate scope, allowing access to desired products in moderate to excellent yields. Notably, this method is distinguished by site-specificity

  据报道，通过自由基-自由基偶联途径，铜催化氨基酸/肽和α-溴酯/酮的选择性α-烷基化过程，这是一种简便有效的方法。该反应表现出优异的官能团耐受性和广泛的底物范围，能够以中等至优异的产率获得所需的产物。值得注意的是，该方法的特点是位点特异性，并且与其他氨基酸单元相比，对芳基甘氨酸基序表现出完全选择性。此外，新型SAHA含苯丙氨酸类似物（SPACA）的有效合成证明了该策略的实用性。
• 3-(异羟肟酸)-孕烯醇酮类缀合物及其制备方法和应用
  申请人：南宁师范大学

  公开号：CN114835770A

  公开（公告）日：2022-08-02

  本发明公开了一种酯基链接的3‑(异羟肟酸)‑孕烯醇酮类缀合物，其化学结构如下式所示： 本发明的3‑酯基链接的孕甾类缀合物对人宫颈癌细胞(HeLa)和人乳腺癌细胞(T47d)具有显著的抑制作用，可以用于制备抗肿瘤药物。
• 20-酰胺-(异羟肟酸)-孕烯醇酮类缀合物及其制备方法
  申请人：南宁师范大学

  公开号：CN114835769A

  公开（公告）日：2022-08-02

  本发明公开了一种酰胺键链接的20‑酰胺‑(异羟肟酸)‑孕烯醇酮类缀合物，其化学结构如下式所示： 本发明的20‑酰胺‑(异羟肟酸)‑孕烯醇酮类缀合物对人乳腺癌细胞(T47d)和人卵巢癌细胞(SKOV3)有显著的抑制作用，可以用于制备抗肿瘤药物。
• Design and synthesis of parthenolide-SAHA hybrids for intervention of drug-resistant acute myeloid leukemia
  作者：Weizhi Ge、Zhongquan Liu、Yu Sun、Tianpeng Wang、Hongyu Guo、Xinyi Chen、Shengzu Li、Mengmeng Wang、Yue Chen、Yahui Ding、Quan Zhang

  DOI：10.1016/j.bioorg.2019.03.056

  日期：2019.6

  A series of parthenolide-SAHA hybrids were synthesized and evaluated for their anti-AML activities against HL-60 and HL-60/ADR cell lines. The most active compound 26 exhibited high activity against HL-60/ADR cell line with IC50 value of 0.15 mu M, which demonstrated 16.8-fold improvement compared to that of the parent compound PTL (IC50, = 2.52 mu M). Moreover, it was six times more potent than the reference drug SAHA (IC50 = 0.90 mu M) and fifty-one times more potent than ADR (IC50 , = 7.72 mu M). The preliminary molecular mechanism of 26 indicated that compound 26 could significantly induce apoptosis of HL-60/ADR cells. The effect of compound 26 was mainly through mitochondria pathway. Further investigation revealed that the protein level of HDAC1 and HDAC6 were reduced after the treatment of compound 26 with a dose-dependent manner. Compound 26 could significantly decrease ABCC1 expression, which increased the accumulation of intracellular drug for overcoming the drug resistance. On the base of these results, compound 26 might be considered as a promising candidate for further evaluation as a potential anti-AML drug.
• Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs)
  作者：Stefan Schäfer、Laura Saunders、Elena Eliseeva、Alfredo Velena、Mira Jung、Andreas Schwienhorst、Anja Strasser、Achim Dickmanns、Ralf Ficner、Sonja Schlimme

  DOI：10.1016/j.bmc.2007.10.092

  日期：2008.2.15

  We synthesized biarylalanine-containing hydroxamic acids and tested them on immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that was confirmed in cells by Western blot (tubulin vs histones). We obtained an X-ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models. Antiproliferative activity was shown on cancer cells for selected compounds.