4-乙氧基-3-硝基苯甲酸甲酯 | 1021292-52-3

• 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: 4-乙氧基-3-硝基苯甲酸甲酯
• 英文名称: methyl 4-ethoxy-3-nitrobenzoate
• 英文别名: methyl 3-nitro-4-ethoxybenzoate
• CAS: 1021292-52-3
• 化学式: C₁₀H₁₁NO₅
• mdl: MFCD12172427
• 分子量: 225.201
• InChiKey: QXCUGYPKDRAMSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-乙氧基-3-硝基苯甲酸甲酯 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 4-乙氧基-3-硝基苯甲酸
  参考文献：
  名称：

  双靶点机制抗SARS-CoV-2联芳酰胺衍生物的设计、合成及生物学评价

  摘要：

  COVID-19 大流行凸显了开发有效小分子抗病毒药物的迫切需要。合成了 33 种新型联芳酰胺衍生物，并评估了其抗冠状病毒活性。一些重要的 SAR 被发现，并且深入的结构修饰产生了最活跃的化合物8b和8h 。 8h的广谱抗冠状病毒作用在RNA和蛋白质水平上得到了验证。 8h在多个阶段抑制冠状病毒复制，从病毒进入到病毒dsRNA 合成。作用机制表明8h可能同时作用于3CL pro和TMPRSS2而发挥抗冠状病毒作用。 8h与RdRp抑制剂联用对冠状病毒表现出协同抑制活性。该研究证实联芳酰胺衍生物可能是一类具有多靶点作用的新型潜在抗冠状病毒治疗药物，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2023.115978
• 作为产物：
  描述：

  对乙氧基苯甲酸 在 氯化亚砜 、 硫酸 、 硝酸 作用下， 反应 1.5h， 生成 4-乙氧基-3-硝基苯甲酸甲酯
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis

  摘要：

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

  DOI：

  10.1021/acs.jmedchem.5b01478

文献信息

• N-(3-硝基-4-烷氧基苯甲酰基)氨基酸类化合物、制备方法及其用途
  申请人：中国医科大学

  公开号：CN110183348B

  公开（公告）日：2022-06-03

  本发明公开了一种N‑（3‑硝基‑4‑烷氧基苯甲酰基）氨基酸类化合物及其制备方法与应用，属于医药领域。通过以4‑羟基‑3‑硝基苯甲酸经甲醇酯化，溴代烷烃取代，水解，氯化，再与L‑苯甘氨酸酰化得得到R2为L‑苯甘氨酸钠盐，水解后得N‑（3‑硝基‑4‑烷氧基苯甲酰基）氨基酸类化合物。本发明公开的N‑（3‑硝基‑4‑烷氧基苯甲酰基）氨基酸类化合物具有新颖的化学结构，在体外黄嘌呤氧化酶抑制活性测试中显现出了良好的效果，可用于痛风疾病的治疗和预防。
• 3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G AND OTHER A3 FAMILY MEMBERS
  申请人：Northwestern University

  公开号：US20160052870A1

  公开（公告）日：2016-02-25

  Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds include 3 -benzamide compounds that may be administered to treat an HIV-1 infection or cancer in a patient.

  本发明涉及一种新型苯甲酰胺化合物及其用途，通过增加患者体内A3G和/或A3家族蛋白的细胞水平来治疗患者需要的疾病和障碍。所披露的化合物包括3-苯甲酰胺化合物，可用于治疗患者的HIV-1感染或癌症。
• [EN] 3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G<br/>[FR] 3-AMIDOBENZAMIDES ET LEURS UTILISATIONS POUR AUGMENTER LES TAUX CELLULAIRES D'A3G
  申请人：UNIV NORTHWESTERN

  公开号：WO2016029136A8

  公开（公告）日：2016-07-07
• US9688637B2
  申请人：——

  公开号：US9688637B2

  公开（公告）日：2017-06-27
• Discovery of 4‐(isopentyloxy)‐3‐nitrobenzamide derivatives as xanthine oxidase inhibitors through a non‐anthraquinone exploration
  作者：Shuai Guo、Qi Sun、Xu Zhang、Song‐ye Li、Hong‐ye Liu、Gong‐hui Ge、Jing Wang、Xing‐yang Liu、Ben Xu、Ting‐ting Li、Xian‐feng Zhou、Yan‐ping Wang、Fan‐hao Meng、Ting‐jian Zhang

  DOI：10.1002/ardp.202400137

  日期：2024.10

  In our previous study, we reported a series of N‐(9,10‐anthraquinone‐2‐carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug‐like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure–activity relationship (SAR) studies, we identified a series of 4‐(isopentyloxy)‐3‐nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4‐isopentyloxy‐N‐(1H‐pyrazol‐3‐yl)‐3‐nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 μM. Compound 6k showed favorable drug‐like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24‐fold improvement in IC50, along with a 1.6‐fold enhancement in LE and a 3.7‐fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug‐like characteristics, thereby warranting further exploration.