4-acetamido-2-hydroxy-5-nitrobenzoic acid | 82378-91-4

• 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: 4-acetamido-2-hydroxy-5-nitrobenzoic acid
• CAS: 82378-91-4
• 化学式: C₉H₈N₂O₆
• 分子量: 240.172
• InChiKey: ANBFDFJFJMWULJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-acetamido-2-hydroxy-5-nitrobenzoic acid 在 盐酸 、 硫酸 、 水 、 铁粉 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 cesium fluoride 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 56.5h， 生成 2-((2,6-dichlorophenyl)amino)-7-methyl-N-(4-(trifluoromethyl)phenyl)-1H-benzofuro[4,5-d]imidazole-5-carboxamide
  参考文献：
  名称：

  Discovery of furan and dihydrofuran-fused tricyclic benzo[ d ]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1

  摘要：

  This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE(2) production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having <50 nM potencies in the A549 cellular assay and adequate metabolic stability in liver microsomes. Lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokinetic properties over other compounds. In particular, 8m revealed satisfactory oral pharmacokinetics and bioavailability in multiple species like rat, guinea pig, dog and cynomolgus monkey. In addition, the representative compound 8m showed in vivo efficacy by inhibiting LPS-induced thermal hyperalgesia with an ED50 of 14.3 mg/kg in guinea pig. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.062
• 作为产物：
  描述：

  4-氨基水杨酸 在 sodium nitrate 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 4-acetamido-2-hydroxy-5-nitrobenzoic acid
  参考文献：
  名称：

  氟化唑类抗结核药物的设计、合成和药理学评价

  摘要：

  描述了作为抗结核药物的 2,2-二甲基-2,3-二氢苯并呋喃系留 1,3,4-恶二唑衍生物的设计、合成和生物筛选。目标化合物的合成通过一系列反应方案进行。所有合成的化合物均通过IR、1H NMR、13C NMR和质谱进行表征。分子对接研究证实了合成化合物的治疗潜力。在合成的化合物中，发现 12a、12c、12d、12e、12g 和 12j 在体外和体外对非复制性结核分枝杆菌 H37Ra 的复制培养物比对复制培养物更有活性。这些化合物的最低抑菌浓度 (MIC) 值在 2.31–23.91 μg/mL 范围内。针对细胞系 THP-1、A549 和 PANC-1 进行细胞毒性研究，并且观察到这些化合物对宿主细胞无毒。用 InhA (FabI/ENR) 进行分子对接，并表明合成化合物的抗分枝杆菌潜力。发现这里提出的调查对于开发针对分枝杆菌感染的新治疗剂是偶然的。

  DOI：

  10.1002/ardp.201700294

文献信息

• HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
  申请人：McCall John M.

  公开号：US20140128392A1

  公开（公告）日：2014-05-08

  Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

  本文披露了新的Formula IIa的杂环化合物及其组合物，以及它们作为治疗疾病的药物的应用。还提供了在人类或动物主体中抑制PAS激酶（PASK）活性的方法，用于治疗糖尿病等疾病。
• 4,5-Diamino-3-Halo-2-Hydroxybenzoic Acid Derivatives and Preparations Thereof
  申请人：LEE AN-RONG

  公开号：US20120101157A1

  公开（公告）日：2012-04-26

  Disclosed are 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives and manufactures thereof. The 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives are presented by formula (I): wherein R 1 group is H, CH 3 , or C 2 H 5 ; R 2 group is H, or Br; R 3 group is CH 3 , or C 3 H 7 ; and R 4 group is H, or C(═NH)—NH 2 . 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives provided here were non-toxic to MDCK cells, particularly compounds 6 a , 6 b , 6 c , 6 e , 6 f , 7 a , 7 b and 8 had better anti-H1N1 activity. In the future, these compounds can be used to focus on viral neuraminidases as targets to develop effective anti-influenza drugs.

  本文披露了4,5-二氨基-3-卤代-2-羟基苯甲酸衍生物及其制备方法。所述4,5-二氨基-3-卤代-2-羟基苯甲酸衍生物由下式（I）表示：其中R1基团为H、CH3或C2H5；R2基团为H或Br；R3基团为 或C3H7；R4基团为H或C(═NH)—NH2。本文提供的4,5-二氨基-3-卤代-2-羟基苯甲酸衍生物对MDCK细胞无毒，特别是化合物6a、6b、6c、6e、6f、7a、7b和8具有更好的抗H1N1活性。未来，这些化合物可以用于将病毒神经氨酸酶作为靶点，开发有效的抗流感药物。
• Heterocyclic compounds for the inhibition of PASK
  申请人：BioEnergenix, LLC

  公开号：US09370522B2

  公开（公告）日：2016-06-21

  Disclosed herein are new heterocyclic compounds having structural Formula IIa and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

  本文披露了具有结构式IIa的新杂环化合物及其组合物，并将其应用于治疗疾病的制药。还提供了抑制人类或动物体内PAS激酶（PASK）活性的方法，用于治疗糖尿病等疾病。
• Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[ d ]imidazole series – Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2
  作者：Nagarajan Muthukaman、Sanjay Deshmukh、Macchindra Tambe、Dnyandeo Pisal、Shital Tondlekar、Mahamadhanif Shaikh、Neelam Sarode、Vidya G. Kattige、Pooja Sawant、Monali Pisat、Vikas Karande、Srinivasa Honnegowda、Abhay Kulkarni、Dayanidhi Behera、Satyawan B. Jadhav、Ramchandra R. Sangana、Girish S. Gudi、Neelima Khairatkar-Joshi、Laxmikant A. Gharat

  DOI：10.1016/j.bmcl.2018.02.048

  日期：2018.4

  In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d] imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED50: 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED50: 106 mg/kg). (C) 2018 Elsevier Ltd. All rights reserved.
• van der Stelt et al., Arzneimittel-Forschung/Drug Research, 1954, vol. 4, p. 544,546
  作者：van der Stelt et al.

  DOI：——

  日期：——