N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide
• 英文别名: N-(6-Hydroxyhexyl)-3,4,5-trimethoxybenzamide
• 化学式: C₁₆H₂₅NO₅
• 分子量: 311.378
• InChiKey: WYCPHSOARJMNCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide 在 碳酸氢钠 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.17h， 生成 α-5-(3,4,5-trimethoxybenzamido)pentyl-N-cyclohexylnitrone
  参考文献：
  名称：

  苯甲酸衍生的硝酮：一类潜在的乙酰胆碱酯酶抑制剂和神经保护剂

  摘要：

  赋予有效和选择性乙酰胆碱酯酶（AChE）和/或丁酰胆碱酯酶（BChE）抑制活性的新化学实体的发现仍然是阿尔茨海默氏病治疗的相关主题。因此，合成了一个小的苯甲酰胺基硝酮文库（化合物24至42），并针对胆碱酯酶进行了筛选。SAR研究表明，叔丁基部分是最有利的硝酮样式。通常，叔丁基衍生物可有效抑制AChE，是最有效的化合物33（IC 50  = 8.3±0.3μM；Ki5.2μM）。数据指出了非竞争性的抑制作用机制，对于标准多奈哌齐也观察到了这种作用。没有化​​合物显示出BChE抑制活性。分子模型研究提供了对酶-抑制剂相互作用的见解，并使实验数据合理化，从而确认了硝酮33和38与AChE的结合模式具有最有利的结合自由能。 的叔-butylnitrones 33和38均不能在不同的细胞系（SH-SY5Y和HepG2）细胞毒性的。此外，化合物33能够预防t -BHP诱导的SH-SY5Y分化细胞中的氧化应激。

  DOI：

  10.1016/j.ejmech.2019.04.026
• 作为产物：
  描述：

  6-氨基-1-己醇 、 3,4,5-三甲氧基苯甲酰氯 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 24.5h， 以93%的产率得到N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide
  参考文献：
  名称：

  Design and synthesis of pyrrolobenzodiazepine-gallic hybrid agents as p53-dependent and -independent apoptogenic signaling in melanoma cells

  摘要：

  A new class of pyrrolo[2,1-c][1,4]benzodiazepine-Gallic hybrid agents (PBD-GA) conjugated through alkyl spacers has been designed and synthesized. The combination of these two core pharmacophores with modification in the C-8 position of the PBD ring with alkyl spacers afforded oxygen-tethered compounds 5a-5d and amide-tethered analogues 11a-11d with improved anticancer activity for two melanoma cell lines, A375 and RPMI7951, differing in their p53 status. The agents 5a-5d were cytotoxic in melanoma compared to agents 11a-11d. In particular, compounds 5b and 5c were found to possess the most potent activity compared with other hybrid agents and were proved with the help of quantitative structure activity relationship studies (QSAR). These PBD conjugates caused S phase arrest for the A375 cell line via increased reactive oxygen species (ROS) generation, deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (ATM)/ATM-Rad3-related (ATR) and checkpoint kinases 1 (Chk1) activation. Moreover, the PBD-GA induced A375 apoptotic cell death followed through p53 (ATM downstream target) increase, B-cell leukemia-xL (Bcl-xL) and mitochondria! membrane potential (Delta Psi(mt)) decrease, cytochrome c release, and caspase-3/Poly Adp Ribose Polymerase (PARP) cleavage. On the other hand, mutant p53 RPMI7951 cell death occurred by PBD-GA-mediated mitochondria- and caspase-dependent pathways via lysosomal membrane permeabilization (LMP), but not through p53 signaling. Finally, compound 5b was shown to reduce murine melanoma size in a mouse model. These results suggest that the PBD-GA could be used as a useful chemotherapeutic agent in melanoma with activated p53 or mutant p53. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.039

文献信息

• Structural elucidation of a series of benzamide derivatives
  作者：Catarina Oliveira、Alexandra Gaspar、Ligia R. Gomes、John N. Low、Fernanda Borges、Fernando Cagide

  DOI：10.1002/mrc.4682

  日期：2018.3

  aliphatic chain with a variable number of carbon atoms, is one of the strategies often used to improve their hydrophobicity and overcome some of the limitations. Within this framework, a complete structural elucidation by one‐ and two‐dimensional (1D and 2D, respectively) NMR, mass spectroscopy, and X‐ray techniques of a series of bromobenzamides of our library containing different spacer length (6‐, 8‐ and

  苯甲酸及其衍生物是对人类健康具有显着益处的化合物，因为它们具有抗氧化、抗炎、抗癌和神经保护等生物学和药理特性。苯甲酸化合物存在于人类日常饮食中，例如水果和蔬菜中。然而，据描述，当摄入这些天然化合物时，这些天然化合物会分布在我们的全身，导致高度可变性或与临床无关的反应，因此难以跨越生物屏障并在特定目标中积累。酚酸的亲脂化，即通过引入由具有可变碳原子数的脂肪链构成的间隔基，是经常用于提高其疏水性并克服一些限制的策略之一。在此框架内，通过一维和二维（分别为 1D 和 2D）核磁共振、质谱和 X 射线技术对我们文库中含有不同间隔长度（6-、8-和 10 个碳脂肪族链）和芳香环中的不同取代基（方案 1）被发现是相关的。最后，为了完成研究，进行了化合物 8（N-(6-溴己基)-3,4,5-三甲氧基苯甲酰胺）的单晶 X 射线晶体学分析。
• [EN] HYDROXYBENZOIC ACID DERIVATIVES, METHODS AND USES THEREOF<br/>[FR] DÉRIVÉS D'ACIDE HYDROXYBENZOÏQUE, PROCÉDÉS ET UTILISATIONS ASSOCIÉS
  申请人：UNIV DO PORTO

  公开号：WO2018122789A1

  公开（公告）日：2018-07-05

  The present disclosure relates to the design and synthesis of new mitochondriotropic antioxidant compounds based on hydroxybenzoic acids and analogues. Furthermore, this disclosure is also related to the methods and uses of the hydroxybenzoic based derivatives and analogues, for example, in the field of human and animal diseases, for instance to treat mitochondrial dysfunction or mitochondrial deficiencies, and cosmetics, for instance to prevent or delay skin aging.

  本公开涉及基于羟基苯甲酸及其类似物的新型线粒体靶向抗氧化剂化合物的设计和合成。此外，本公开还涉及基于羟基苯甲酸衍生物和类似物的方法和用途，例如在人类和动物疾病领域中，例如用于治疗线粒体功能障碍或线粒体缺陷，以及在化妆品领域中，例如用于预防或延缓皮肤衰老。
• Hydroxybenzoic acid derivatives, methods and uses thereof
  申请人：UNiVERSIDADE DO PORTO

  公开号：US11078222B2

  公开（公告）日：2021-08-03

  The present disclosure relates to the design and synthesis of new mitochondriotropic antioxidant compounds based on hydroxybenzoic acids and analogues. Furthermore, this disclosure is also related to the methods and uses of the hydroxybenzoic based derivatives and analogues, for example, in the field of human and animal diseases, for instance to treat mitochondrial dysfunction or mitochondrial deficiencies, and cosmetics, for instance to prevent or delay skin aging.

  本公开涉及基于羟基苯甲酸及其类似物的新型线粒体抗氧化化合物的设计和合成。此外，本公开还涉及基于羟基苯甲酸的衍生物和类似物的方法和用途，例如，在人类和动物疾病领域，例如治疗线粒体功能障碍或线粒体缺陷，以及化妆品领域，例如防止或延缓皮肤老化。
• Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction
  作者：S. Benfeito、C. Oliveira、C. Fernandes、F. Cagide、J. Teixeira、R. Amorim、J. Garrido、C. Martins、B. Sarmento、R. Silva、F. Remião、E. Uriarte、P.J. Oliveira、F. Borges

  DOI：10.1016/j.ejmech.2019.01.055

  日期：2019.4

  Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained. Overall, mitochondriotropic antioxidants showed remarkable antioxidant and chelating properties, presenting low cytotoxic effects on human differentiated neuronal (SH-SY5Y) and hepatocarcinoma (HepG2) cells and exhibited neuroprotective properties on SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2) oxidative insults. Moreover, compounds 58, 59, 62, 63, 66 and 67 were able to permeate a layer of hCMEC/D3 cells in a time-dependent manner. Mitochondriotropic antioxidant 67 stands out by its remarkable iron chelating and neuroprotective properties toward both H2O2 and 6-OHDA-induced oxidative damage, drug-like properties and BBB permeability. (C) 2019 Elsevier Masson SAS. All rights reserved.
• HYDROXYBENZOIC ACID DERIVATIVES, METHODS AND USES THEREOF
  申请人：Universidade do Porto

  公开号：EP3562830A1

  公开（公告）日：2019-11-06