3,4,5-trihydroxy-N-hexyl-benzamide | 99504-50-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,4,5-trihydroxy-N-hexyl-benzamide
• 英文别名: hexyl gallamide；HGA；N-Hexyl-3,4,5-trihydroxybenzamide
• CAS: 99504-50-4
• 化学式: C₁₃H₁₉NO₄
• 分子量: 253.298
• InChiKey: YCWCKSIMYUUPKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4,5-trihydroxy-N-hexyl-benzamide 、 3-甲氧基儿茶酚 在 双氧水 、 horseradish peroxidase 作用下， 以 aq. phosphate buffer 、 丙酮 为溶剂， 以42%的产率得到N-hexyl-3,4,6-trihydroxy-2-methoxy-5-oxo-5H-benzo[7]annulene-8-carboxamide
  参考文献：
  名称：

  发现 TLR1/TLR2 复合物的小分子抑制剂

  摘要：

  作为先天免疫的重要调节剂， Toll 样受体 1 和 2 (TLR1/TLR2) 的蛋白质复合物为治疗各种免疫疾病提供了一个有吸引力的靶点。新型化合物 CU-CPT22 可以与特异性脂蛋白配体竞争结合 TLR1/TLR2（见图），具有高抑制活性和特异性。还观察到来自 TNF-α 和 IL-1β 的下游信号受到抑制。

  DOI：

  10.1002/anie.201204910
• 作为产物：
  描述：

  没食子酸 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 3,4,5-trihydroxy-N-hexyl-benzamide
  参考文献：
  名称：

  发现 TLR1/TLR2 复合物的小分子抑制剂

  摘要：

  作为先天免疫的重要调节剂， Toll 样受体 1 和 2 (TLR1/TLR2) 的蛋白质复合物为治疗各种免疫疾病提供了一个有吸引力的靶点。新型化合物 CU-CPT22 可以与特异性脂蛋白配体竞争结合 TLR1/TLR2（见图），具有高抑制活性和特异性。还观察到来自 TNF-α 和 IL-1β 的下游信号受到抑制。

  DOI：

  10.1002/anie.201204910

文献信息

• Synthesis and evaluation of novel benzotropolones as Atg4B inhibiting autophagy blockers
  作者：Muhammet Tanc、Matthias Cleenewerck、Ammar Kurdi、Ria Roelandt、Wim Declercq、Guido De Meyer、Koen Augustyns、Wim Martinet、Pieter Van der Veken

  DOI：10.1016/j.bioorg.2019.03.021

  日期：2019.6

  treatments for these diseases. Inhibitors of autophagy have been proposed as a therapeutic intervention in, e.g., advanced cancer, and inhibiting the cysteine protease Atg4B has been put forward as a main strategy to block autophagy. We recently identified and demonstrated -both in vitro and in vivo - that compounds with a benzotropolone basic structure targeting Atg4B, can significantly slow down tumor

  自噬是一种细胞内降解/再循环途径，可为细胞代谢提供营养和构成要素，并使细胞质清除过时的蛋白质和细胞器。近年来，据报道自噬活性失调是许多不同疾病类型的特征，包括癌症和神经退行性疾病。这为开发自噬调节化合物作为这些疾病的潜在治疗方法提供了有力的依据。已经提出自噬抑制剂作为例如晚期癌症的治疗干预，并且已提出抑制半胱氨酸蛋白酶Atg4B作为阻断自噬的主要策略。我们最近在体内和体外鉴定并证明了-具有针对Atg4B的苯并马酚基础结构的化合物可以显着减慢肿瘤的生长并增强经典化学疗法的作用。在这项研究中，我们报告了在6个不同位置具有其他结构修饰的新苯并三氮杂环丙烷衍生物的合成和抑制作用。为了获得固体抑制谱，对所有化合物进行了三个水平的评估，包括两次基于细胞的测定以确认自噬和细胞内Atg4B抑制作用，以及一次基于SDS-PAGE的实验以评估体外Atg4B亲和力。鉴定了几种具有良好前景的分子。
• Synthesis and Anticancer Effect of 3,4,5-N-Alkyl-Benzamides on Colon Carcinoma HCT- 116 Cells
  作者：Jilly Octaria Tagore Chan、Ade Arsianti、Maurin Marcelia、Stevano Julio Wijoyo、Fadilah Fadilah、Rista Putrianingsih、Norma Nur Azizah、Hiroki Tanimoto、Kiyomi Kakiuchi

  DOI：10.13005/ojc/340323

  日期：2018.6.28

  The natural phenolic gallic acid has demonstrated a significant inhibition of cell proliferation in a series of cancer cell lines, as well as induced apoptosis in  HCT-116 colon cancer cells. This research aims to synthesize six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide derivatives of  gallic acid, and investigate its anticancer effect on colon carcinoma HCT-116 cells.Six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide, namely 3,4,5-trihydroxy-N-methyl-benzamide (2); 3,4,5-trihydroxy-N-ethyl-benzamide (3); 3,4,5-trihydroxy-N-butyl-benzamide (4); 3,4,5-trihydroxy-N-sec-butyl-benzamide (5); 3,4,5-trihydroxy-N-tert-butyl-benzamide (6) and 3,4,5-trihydroxy-N-hexyl-benzamide (7), have been successfully synthesized by amidation of carboxyl group of gallic acid with six corresponding alkylamines, respectively. Furthermore, anticancer effect of these six synthesized derivatives on colon HCT-116 cells were examined by MTT assay. Data were analyzed by linear regression method to generate IC50 value. The results will be compared with gallic acid as an original compound and doxorubicine as a positive control.Amidation of gallic acid with six corresponding alkylamines gave desired -N-methyl-, -N-ethyl-, -N-butyl-, -N-sec-butyl-, -N-ters-butyl-, and –N-hexyl benzamide with yield ranging from 18% to 84%. Compared to gallic acid (IC50: 0.05 µM) and doxorubicine (IC50: 0.001 µM), all these six synthesized derivatives showed a lower anticancer effect on colon HCT-116 cells. The strongest anticancer and inhibitory effect on HCT-116 cells has shown by 3,4,5-trihydroxy-N-hexyl benzamide (7) with IC50 value of 0.07 µM. Our results suggested that 3,4,5-trihydroxy-N-hexyl benzamide (7) is a potential to be developed as a promising anti-colon cancer agent.

  16细胞。
• Antiproliferative and apoptosis-inducing activities of alkyl gallate and gallamide derivatives related to (−)-epigallocatechin gallate
  作者：Kosuke Dodo、Taro Minato、Tomomi Noguchi-Yachide、Masami Suganuma、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2008.07.063

  日期：2008.9

  Green tea and (-)-epigallocatechin gallate (EGCG: one of the main components of green tea) are reported to have cancer-preventive activity in humans. A previous SAR study of EGCG and derivatives indicated that a galloyl group is essential for the activity. To test this hypothesis, we synthesized various alkyl gallate and gallamide derivatives and evaluated their antiproliferative effects on human leukemia HL-60 cells. Dodecyl 3,4,5-trihydroxybenzoate (6c) showed the most potent activity, being more potent than EGCG. To clarify the molecular mechanism of the antiproliferative action, we investigated the effects of 6c on various factors. Compound 6c was found to induce apoptosis mediated by endoplasmic reticulum (ER)-stress-related caspase-12. Upregulation of gadd-153, an ER-stress marker protein, was also observed. These results indicate that 6c induced apoptosis via the ER-stress-related pathway. (C) 2008 Elsevier Ltd. All rights reserved.
• OGATA, JOSITAKEH;TANAKA, ISAO;IKEHDA, MAKOTO;XARADA, KOKITI;FUDZIMORI, TO+
  作者：OGATA, JOSITAKEH、TANAKA, ISAO、IKEHDA, MAKOTO、XARADA, KOKITI、FUDZIMORI, TO+

  DOI：——

  日期：——
• JPS60199850A
  申请人：——

  公开号：JPS60199850A

  公开（公告）日：1985-10-09