5-氯-N-(3,4-二甲氧基苯基)-2-羟基苯甲酰胺 | 634186-43-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-氯-N-(3,4-二甲氧基苯基)-2-羟基苯甲酰胺
• 英文名称: 5-chloro-N-(3,4-dimethoxyphenyl)-2-hydroxybenzamide
• CAS: 634186-43-9
• 化学式: C₁₅H₁₄ClNO₄
• 分子量: 307.733
• InChiKey: MZPYUKJNSRUBMW-UHFFFAOYSA-N

物化性质

• 沸点：
  394.5±42.0 °C(Predicted)
• 密度：
  1.357±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 、 3,4-二甲氧基苯胺 在 4-二甲氨基吡啶 、 1,2-二氯乙烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以24.1 %的产率得到5-氯-N-(3,4-二甲氧基苯基)-2-羟基苯甲酰胺
  参考文献：
  名称：

  N-苯基苯甲酰胺类似物对被忽视的疾病病原体曼氏血吸虫的活性

  摘要：

  对于曼氏血吸虫扁虫病原体，我们报告了N-苯基苯甲酰胺化合物1 ( MMV687807 ) 的 25 种衍生物的结构-活性关系，该化合物是一种疟疾风险药物药物化合物，最初于 2018 年鉴定出其生物活性。合成的化合物经过交叉筛选针对 HEK 293 哺乳动物细胞。化合物9和11被鉴定为速效杀血吸虫化合物，成虫完整性在 1 小时内受到严重损害。针对 HEK 293 哺乳动物细胞，两种化合物均表现出高 CC 50值（分别为 9.8 ± 1.6 和 11.1 ± 0.2 µM），这可以转化为舒适的选择性。当以浓度-反应形式进行评估时，化合物9在纳摩尔范围内具有活性 (EC 50 = 80 nM)，相对于 HEK 293 细胞，选择性指数为 123。这些数据鼓励进一步研究N-苯基苯甲酰胺作为抗血吸虫药。

  DOI：

  10.1016/j.bmcl.2023.129164

文献信息

• <p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>
  作者：Jens Hagenow、Stefanie Hagenow、Kathrin Grau、Mohammad Khanfar、Lena Hefke、Ewgenij Proschak、Holger Stark

  DOI：10.2147/dddt.s236586

  日期：——

  Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors.Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results.Results: N-(2,4-Dinitrophenyl)benzo [d] [1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC50 = 56 nM, K-i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites.Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.
• Salicylanilide Inhibitors of Toxoplasma gondii
  作者：Alina Fomovska、Richard D. Wood、Ernest Mui、Jitenter P. Dubey、Leandra R. Ferreira、Mark R. Hickman、Patricia J. Lee、Susan E. Leed、Jennifer M. Auschwitz、William J. Welsh、Caroline Sommerville、Stuart Woods、Craig Roberts、Rima McLeod

  DOI：10.1021/jm3007596

  日期：2012.10.11

  Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose antiapicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles.
• Identification and synthesis of low-molecular weight cholecystokinin B receptor (CCKBR) agonists as mediators of long-term synaptic potentiation
  作者：Yanmei Zhang、Yican Wang、Yiping Guo、Jinxi Liao、Zhengchao Tu、Yongzhi Lu、Ke Ding、Micky D. Tortorella、Jufang He

  DOI：10.1007/s00044-019-02292-x

  日期：2019.3

  Recently, He et al. reported that CCKB receptors located in the neocortex of the brain when bound to their bound natural ligand, CCK peptides, enhance memory, bringing up the possibility that agonists targeting the CCKB receptor may act as therapeutic agents in diseases in which memory loss is marked as observed in dementia and Alzheimer's. In this report, we describe the synthesis of novel low-molecular weight benzoamine CCKB receptor agonists. The compounds made in this series were determined to be mostly partial agonists, although some antagonists were identified, as well, capable of triggering calcium release in a cell line that overexpresses the CCKB receptor. Compound 35 demonstrated an EC50 of 0.15 mu M in the cell-based assay, but more importantly, several of the compounds, including 35, demonstrated a physiological effect, inducing long-term potentiation in rat brains comparable to the CCK-8 peptide albeit at much higher concentrations. Based on these findings, benzoamines may be the basis for a new series of CCKB receptor agonists in drug-discovery efforts that seek to develop therapeutics to prevent memory loss.
• [EN] GLUTAMATE RECEPTOR MODULATORS AND THERAPEUTIC AGENTS<br/>[FR] MODULATEURS DES RÉCEPTEURS AU GLUTAMATE ET AGENTS THÉRAPEUTIQUES
  申请人：WOOD RICHARD D

  公开号：WO2010101648A1

  公开（公告）日：2010-09-10

  The present invention discloses methods of modulating the activity of Group I mGluRs using a defined class of benzamide compounds. In one embodiment, methods of modulating the activity of mGluR1 are provided. In another embodiment, methods of modulating the activity of mGluR5 are provided. In still another embodiment, methods of simultaneously modulating the activities of both mGluR1 and mGluR5 are provided. The present invention also provides methods of treating diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of benzamide compounds. The present invention further provides methods of preventing diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of compounds. Diseases and disorders contemplated include, inter alia, diseases and disorders of the central nervous system, the peripheral nervous system, the gastrointestinal system, the circulatory system, skin, retina, brain, heart, and lungs.