1,3-二氟-4-碘-2-甲氧基苯 | 220353-18-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 1,3-二氟-4-碘-2-甲氧基苯
• 英文名称: 1,3-difluoro-4-iodo-2-methoxybenzene
• 英文别名: 2,6-Difluoro-3-iodoanisole
• CAS: 220353-18-4
• 化学式: C₇H₅F₂IO
• 分子量: 270.017
• InChiKey: SDPBQRPKIIKJLV-UHFFFAOYSA-N

物化性质

• 熔点：
  28-29 °C
• 沸点：
  252.1±35.0 °C(Predicted)
• 密度：
  1.876±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-二氟-4-碘-2-甲氧基苯 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 2,4-二氟-3-甲氧基苄胺
  参考文献：
  名称：

  2,6-Difluorophenol as a Bioisostere of a Carboxylic Acid:  Bioisosteric Analogues of γ-Aminobutyric Acid

  摘要：

  3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2,6-difluorophenol (7) were synthesized in eight and four steps, respectively, starting from 2,6-difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain gamma-aminobutyric acid aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme, indicating that the 2,6-difluorophenol moiety appears to be able to substitute for a carboxylic acid to increase the lipophilicity of drug candidates.

  DOI：

  10.1021/jm980435l
• 作为产物：
  描述：

  2,6-二氟苯酚 在 palladium on activated charcoal 硫酸 、 氢气 、 碘 、 硝酸 、 铜 、 碳酸氢钠 、 potassium carbonate 、 sodium nitrite 作用下， 以 溶剂黄146 、 乙酸乙酯 、 丙酮 为溶剂， 反应 9.5h， 生成 1,3-二氟-4-碘-2-甲氧基苯
  参考文献：
  名称：

  2,6-Difluorophenol as a Bioisostere of a Carboxylic Acid:  Bioisosteric Analogues of γ-Aminobutyric Acid

  摘要：

  3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2,6-difluorophenol (7) were synthesized in eight and four steps, respectively, starting from 2,6-difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain gamma-aminobutyric acid aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme, indicating that the 2,6-difluorophenol moiety appears to be able to substitute for a carboxylic acid to increase the lipophilicity of drug candidates.

  DOI：

  10.1021/jm980435l

文献信息

• TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
  申请人：Arvinas, Inc.

  公开号：US20180155322A1

  公开（公告）日：2018-06-07

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作雌激素受体（目标蛋白）的调节剂。特别是，本公开涉及包含在一段至少有一种Von Hippel-Lindau配体、一种cereblon配体、凋亡抑制蛋白配体、小鼠双分钟同源2配体或其组合的双功能化合物，这些配体与相应的E3泛素连接酶结合，在另一端有一个与目标蛋白结合的部分，使得目标蛋白被置于泛素连接酶附近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白降解/抑制相关的广泛药理活性。可以通过本公开的化合物和组合物治疗或预防由目标蛋白聚集或积累引起的疾病或障碍。
• N-substituted Pyrrole-based Scaffolds as Potential Anticancer and Antiviral Lead Structures
  作者：Kyriaki Pegklidou、Nikolaos Papastavrou、Petros Gkizis、Dimitrios Komiotis、Jan Balzarini、Ioannis Nicolaou

  DOI：10.2174/1573406411666150313161225

  日期：2015.7.24

  Undoubtedly, efficient cancer treatment has been a significant challenge for the scientific community over the last decades. Despite tremendous progress made towards this direction, there are still efforts needed to discover new anticancer drugs. In this work, a series of N-substituted pyrrolebased scaffolds have been synthesized and evaluated for antiproliferative activity against a panel of cancer cell lines (L1210, CEM and HeLa). Furthermore, in order to discover new scaffolds as antiviral agents, all the examined compounds were evaluated for activity against different types of DNA and RNA viruses. The key feature of the above structures is the existence of an aromatic ring with at least one hydrogen-bonding donor and acceptor group. Results have shown noteworthy cytostatic activity for three of the synthesized compounds (1, 3 and 9). Especially, compound 1, containing a tropolone ring, proved to be the most promising scaffold (IC50:10-14 µM ) for the development of novel potential anticancer agents. In addition, compound 1 has shown modest anti-HSV-1, -HSV2 activity in HEL cell cultures (EC50: 27-40 µM).

  毫无疑问，高效的癌症治疗在过去几十年里一直是科学界面临的重大挑战。尽管在这方面取得了巨大的进展，但仍需要努力发现新的抗癌药物。在这项研究中，合成了一系列N取代吡咯基框架，并评估其对一组癌细胞系（L1210、CEM和HeLa）的抗增殖活性。此外，为了发现新的作为抗病毒剂的框架，所有被检验的化合物都被评估了对不同类型的DNA和RNA病毒的活性。这些结构的一个关键特征是存在一个含有至少一个氢键供体和受体基团的芳香环。结果显示，合成的三种化合物（1、3和9）具有显著的细胞静止活性。特别是，含有特罗波隆环的化合物1被证明是最有前景的框架（IC50：10-14 μM），适用于开发新的潜在抗癌药物。此外，化合物1在HEL细胞培养中表现出中等的抗HSV-1和HSV-2活性（EC50：27-40 μM）。
• Structure–activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity
  作者：Maria Chatzopoulou、Eduard Mamadou、Maria Juskova、Cathrine Koukoulitsa、Ioannis Nicolaou、Milan Stefek、Vassilis J. Demopoulos

  DOI：10.1016/j.bmc.2011.01.009

  日期：2011.2

  Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b–c and 5a–c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order

  基于我们以前的工作，我们研究了甲氧基取代的影响以及4a [（1-（3,5-difluoro-4-hydroxyphenyl）-1 H -pyrrol-3-yl ）（苯基）甲酮]。在此基础上，合成了化合物4b–c和5a–c，并测定了醛糖和醛还原酶的抑制活性。此外，研究了4，6-二氟-5-羟基苯基图案（9），以验证酚部分的最佳位置。化合物5b成为最有效和选择性的抑制剂。此外，进一步的分析证明了5b作为有效的抗氧化剂和山梨糖醇在离体大鼠晶状体中的抑制剂。结合以上属性，5b可以作为针对长期糖尿病并发症的先导化合物。
• ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS
  申请人：Thomas Abraham

  公开号：US20080182851A1

  公开（公告）日：2008-07-31

  The present invention provides Stearoyl CoA Desaturase (SCD) inhibitors. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase 1 (SCD1) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase (SCD) inhibitors.

  本发明提供了硬脂酰辅酶A脱饱和酶（SCD）抑制剂。特别地，本文描述的化合物对于治疗或预防由硬脂酰辅酶A脱饱和酶1（SCD1）抑制剂调节的疾病、症状和/或疾病具有用处。本文还提供了制备上述化合物的过程、用于其合成的中间体、其制药组合物以及治疗或预防由硬脂酰辅酶A脱饱和酶（SCD）抑制剂调节的疾病、症状和/或疾病的方法。
• [EN] ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS<br/>[FR] DÉRIVÉS D'ACÉTYLÈNE COMME INHIBITEURS DE LA STÉAROYL COA DÉSATURASE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2008062276A3

  公开（公告）日：2009-03-05