5-methoxybiphenyl-3-carboxylic acid | 1214369-81-9

• 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: 5-methoxybiphenyl-3-carboxylic acid
• 英文别名: 5-Methoxy-3-phenylbenzoic acid；3-methoxy-5-phenylbenzoic acid
• CAS: 1214369-81-9
• 化学式: C₁₄H₁₂O₃
• 分子量: 228.247
• InChiKey: RJNXRRZKLNCRKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methoxybiphenyl-3-carboxylic acid 在 氯化亚砜 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.5h， 生成
  参考文献：
  名称：

  Bifunctional Organocatalysts for the Enantioselective Synthesis of Axially Chiral Isoquinoline N-Oxides

  摘要：

  Bifunctional catalysts bearing amino and urea functional groups have been applied for a novel, highly enantioselective synthesis of axially chiral isoquinoline N-oxides, which are promising chiral ligands or organocatalysts in organic synthesis. This is the first example of highly enantioselective synthesis of axially chiral biaryls by bifunctional organocatalysts. Good-to-excellent enantioselectivities were obtained with a range of substrates.

  DOI：

  10.1021/jacs.5b04151
• 作为产物：
  描述：

  3-溴-5-甲氧基-苯甲酸乙酯 在 四(三苯基膦)钯 、 lithium hydroxide monohydrate 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 5-methoxybiphenyl-3-carboxylic acid
  参考文献：
  名称：

  Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections

  摘要：

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.

  DOI：

  10.1021/jm400416u

文献信息

• Development of 4,5-dihydro-benzodiazepinone derivatives as a new chemical series of BRD4 inhibitors
  作者：Jie Li、Peiqi Wang、Bihui Zhou、Jianyou Shi、Jie Liu、Xiangrong Li、Limei Fan、Yaxin Zheng、Liang Ouyang

  DOI：10.1016/j.ejmech.2016.05.057

  日期：2016.10

  two BRDs termed BD1 and BD2, has emerged as an attractive candidate for the development of inhibitors targeting gene transcription in several types of cancers. In this study, we made structural modifications of previously reported BRD4 inhibitors, to develop new chemical scaffold 3,4-dihydroquinoxalin-2(1H)-one. Four series of compounds (compounds 7–10) were synthesized, and the BRD4-inhibitory activity

  溴结构域（BRD）是蛋白质相互作用模块，可选择性识别ε-N-赖氨酸残基，充当关键的表观遗传读取器，并在基因转录的表观遗传调控中发挥关键作用。含溴结构域的蛋白质4（BRD4）是一种含有两个称为BD1和BD2的BRD的蛋白质，已成为在几种类型的癌症中开发靶向基因转录的抑制剂的诱人候选物。在这项研究中，我们对先前报道的BRD4抑制剂进行了结构修饰，以开发新的化学支架3,4-dihydroquinoxalin-2（1H）-one。合成了四个系列的化合物（化合物7-10），并评估了这些化合物的BRD4抑制活性和抗增殖作用。我们找到化合物10d对白血病细胞具有显着的抗增殖活性，并可以通过线粒体途径诱导细胞凋亡。值得注意的是，分子对接的分析表明，疏水性相互作用对于化合物10d与BD1的结合至关重要。总之，这些结果证明了化合物10d在将来的白血病治疗中可用作具有凋亡诱导作用的BRD4抑制剂的潜力。
• Polymyxin Derivates Useful As Antibacterial Agents
  申请人：Magee Thomas Victor

  公开号：US20120316105A1

  公开（公告）日：2012-12-13

  The present invention provides a new class of polymyxin derivates useful for treating bacterial infections, especially Gram-negative infections, that have reduced renal cytotoxicity.

  本发明提供了一种新的聚霉素衍生物类别，用于治疗细菌感染，特别是革兰氏阴性菌感染，并且具有降低肾细胞毒性的特性。
• Inhibiting fatty acid synthase (FASN)
  申请人：FORMA Therapeutics, Inc.

  公开号：US11299484B2

  公开（公告）日：2022-04-12

  The present disclosure is directed to inhibitors of FASN. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of FASN. For instance, the disclosure is concerned with compounds and compositions for inhibition of FASN, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of FASN, and methods of synthesis of these compounds.

  本公开涉及FASN抑制剂。所述化合物可用于治疗与FASN抑制相关的疾病或紊乱。例如，本公开涉及用于抑制FASN的化合物和组合物、治疗、预防或改善与FASN抑制相关的疾病或紊乱的方法，以及这些化合物的合成方法。
• Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design
  作者：Bryan C. Duffy、Shuang Liu、Gregory S. Martin、Ruifang Wang、Ming Min Hsia、He Zhao、Cheng Guo、Michael Ellis、John F. Quinn、Olesya A. Kharenko、Karen Norek、Emily M. Gesner、Peter R. Young、Kevin G. McLure、Gregory S. Wagner、Damodharan Lakshminarasimhan、Andre White、Robert K. Suto、Henrik C. Hansen、Douglas B. Kitchen

  DOI：10.1016/j.bmcl.2015.04.107

  日期：2015.7

  Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low mu M level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). (C) 2015 Elsevier Ltd. All rights reserved.
• INHIBITING FATTY ACID SYNTHASE (FASN)
  申请人：FORMA Therapeutics, Inc.

  公开号：US20200115368A1

  公开（公告）日：2020-04-16

  The present disclosure is directed to inhibitors of FASN. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of FASN. For instance, the disclosure is concerned with compounds and compositions for inhibition of FASN, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of FASN, and methods of synthesis of these compounds.