2-[(4-苯基苯基)甲氧基]异吲哚-1,3-二酮 | 1885-53-6

• 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: 2-[(4-苯基苯基)甲氧基]异吲哚-1,3-二酮
• 英文名称: N-(4-Phenylbenzyloxy)phthalimide
• 英文别名: 2-([1,1'-biphenyl]-4-ylmethoxy)isoindoline-1,3-dione；N-(4-Phenyl-benzyloxy)-phthalimid；2-(biphenyl-4-ylmethoxy)isoindoline-1,3-dione；N-biphenyl-4-ylmethoxy-phthalimide；2-[(4-phenylphenyl)methoxy]isoindole-1,3-dione
• CAS: 1885-53-6
• 化学式: C₂₁H₁₅NO₃
• 分子量: 329.355
• InChiKey: JYUSHNFOXUEQIH-UHFFFAOYSA-N

物化性质

• 沸点：
  516.6±53.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(4-苯基苯基)甲氧基]异吲哚-1,3-二酮 在 碳酸氢钠 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-(2-Amino-ethyl)-O-biphenyl-4-ylmethyl-hydroxylamine
  参考文献：
  名称：

  1-Benzyloxy-4,5-dihydro-1H-imidazol-2-yl-amines, a novel class of NR1/2B subtype selective NMDA receptor antagonists

  摘要：

  Screening of the Roche compound depository led to the identification of (1-benzyloxy-4,5-dihydro-1H-imidazol-2-yl)-butyl amine 4, a structurally novel NR1/2B Subtype selective NMDA receptor antagonist. The structure-activity relationships developed in this series resulted in the discovery of a novel class of potent and selective NMDA receptor blockers displaying activity in vivo. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00713-3
• 作为产物：
  描述：

  对苯基苯甲醛 在 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 2-[(4-苯基苯基)甲氧基]异吲哚-1,3-二酮
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028

文献信息

• Rh(III)-Catalyzed C–H Amidation of Arenes with <i>N</i>-Methoxyamide as an Amidating Reagent
  作者：Guodong Ju、Guobao Li、Guanwen Qian、Jingyu Zhang、Yingsheng Zhao

  DOI：10.1021/acs.orglett.9b02625

  日期：2019.9.20

  The Rh(III)-catalyzed amidation of C(sp2)-H bonds has been reported by employing the N-methoxyamide as a novel amino source. An excellent level of functional group tolerance can be achieved when N-methoxyamide derivatives are used as the amidating reagents. Importantly, several known bioactive compounds such as Aminalon, Pregabalin, Gabapentin, and Probenecid can be transformed to effective amidating

  通过使用N-甲氧基酰胺作为新型氨基源，已经报道了Rh（III）催化的C（sp2）-H键的酰胺化反应。当使用N-甲氧基酰胺衍生物作为酰胺化试剂时，可以达到极好的官能团耐受性。重要的是，可以将几种已知的生物活性化合物（例如阿米那隆，普瑞巴林，加巴喷丁和丙磺舒）转化为有效的酰胺化试剂，以利于开发新的生物活性分子。
• Benzylic C–H heteroarylation of <i>N</i>-(benzyloxy)phthalimides with cyanopyridines enabled by photoredox 1,2-hydrogen atom transfer
  作者：Long-Jin Zhong、Hong-Yu Wang、Xuan-Hui Ouyang、Jin-Heng Li、De-Lie An

  DOI：10.1039/d0cc03619f

  日期：——

  A visible light initiated α-C(sp3)–H arylation of N-(benzyloxy)phthalimides with cyanopyridines for the construction of highly valuable pyridinyl-containing diarylmethanols, including bioactive motif-based analogues, is reported. This method enables arylation of the C(sp3)–H bonds adjacent to an oxygen atom through alkoxy radical formation by O–N bond cleavage, 1,2-hydrogen atom transfer (HAT), arylation

  据报道，可见光引发了N-（苄氧基）邻苯二甲酰亚胺与氰基吡啶的α-C（sp 3）-H芳基化反应，用于构建高度有价值的含吡啶基二芳基甲醇，包括基于生物活性基序的类似物。这种方法通过O-N键裂解，1,2-氢原子转移（HAT），芳基化和C-CN键裂解级联，通过与烷氧基基团相邻的氧原子进行C（sp 3）-H键芳基化，并提供了一种利用1,2-HAT模式并入官能团以构建官能化醇的方法。
• Alkylation of Allyl/Alkenyl Sulfones by Deoxygenation of Alkoxyl Radicals
  作者：Jia-Bin Han、Ao Guo、Xiang-Ying Tang

  DOI：10.1002/chem.201806138

  日期：2019.2.26

  challenging deoxygenation of alkoxyl radicals from readily accessible alcohol derivatives was developed, affording facile synthesis of functionalized alkenes with good functional group tolerance under mild reaction conditions. Because alkoxyl radicals can easily undergo β‐fragmentations or hydrogen abstractions, this new strategy for deoxygenation of alkoxyl radicals is highly valuable. Moreover, mechanistic

  从容易获得的醇衍生物开发了具有挑战性的烷氧基自由基脱氧剂，可在温和的反应条件下轻松合成具有良好官能团耐受性的官能化烯烃。由于烷氧基自由基很容易发生β片段分解或夺氢现象，因此这种使烷氧基自由基脱氧的新策略非常有价值。此外，机理研究表明，电子中性膦可作为脱氧剂。
• Toward the rational development of peptidomimetic analogs of the C-terminal endothelin hexapeptide: development of a theoretical model
  作者：M. Macchia、S. Barontini、F. Ceccarelli、C. Galoppini、L. Giusti、M. Hamdan、A. Lucacchini、A. Martinelli、E. Menchini、M.R. Mazzoni、R.P. Revoltella、F. Romagnoli、P. Rovero

  DOI：10.1016/s0014-827x(98)00064-0

  日期：1998.8

  C-terminal hexapeptide ET(16-21), His-Leu-Asp-Ile-Ile-Trp, is the minimum ET fragment which maintains biological activity in some, but not all the tissues responding to ETs. Subsequently, other authors described a series of analogs of this peptide, in which the His 16 residue was replaced by non-natural amino acids, characterized by bulky aromatic side chains. Among them, two well-characterized non-selective

  在有关内皮素（ET）肽的结构-活性关系的早期报道中，据报道C端六肽ET（16-21）His-Leu-Asp-Ile-Ile-Trp是最小的ET片段在某些但并非所有对ETs有反应的组织中保持生物活性。随后，其他作者描述了该肽的一系列类似物，其中His 16残基被非天然氨基酸取代，其特征是庞大的芳香族侧链。其中，两种很好表征的非选择性ETA / ETB拮抗剂为PD 142893和PD 145065；但是，由于它们的肽结构降低了对这些有效的ET拮抗剂的兴趣，这可能导致不良的特性，例如不良的生物利用度和短的作用时间。在这些前提的基础上，我们以前的研究基于以（E）-N-（苄氧基）亚氨基酰基部分取代ET（16-21）的His 16残基，开发了ET受体的拟肽配体（化合物3）；化合物3被证明对ET受体具有一定的亲和力，尽管比PD 142893和PD 145065所显示的亲和力低。我们在这里报道了化合物4-12的ETA
• Binding Inhibitors of the Bacterial Sliding Clamp by Design
  作者：Gene Wijffels、Wynona M. Johnson、Aaron J. Oakley、Kathleen Turner、V. Chandana Epa、Susan J. Briscoe、Mitchell Polley、Andris J. Liepa、Albert Hofmann、Jens Buchardt、Caspar Christensen、Pavel Prosselkov、Brian P. Dalrymple、Paul F. Alewood、Philip A. Jennings、Nicholas E. Dixon、David A. Winkler

  DOI：10.1021/jm2004333

  日期：2011.7.14

  The bacterial replisome is a target for the development of new antibiotics to combat drug resistant strains. The beta(2) sliding clamp is an essential component of the replicative machinery, providing a platform for recruitment and function of other replisomal components and ensuring polymerase processivity during DNA replication and repair. A single binding region of the clamp is utilized by its binding partners, which all contain conserved binding motifs. The C-terminal Leu and Phe residues of these motifs are integral to the binding interaction. We acquired three-dimensional structural information on the binding site in beta(2) by a study of the binding of modified peptides. Development of a three-dimensional pharmacophore based on the C-terminal dipeptide of the motif enabled identification of compounds that on further development inhibited alpha-beta(2) interaction at low micromolar concentrations. We report the crystal structure of the complex containing one of these inhibitors, a biphenyl oxime, bound to beta(2), as a starting point for further inhibitor design.