N-benzyl-O-(4-bromobenzoyl)hydroxylamine

• 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: N-benzyl-O-(4-bromobenzoyl)hydroxylamine
• 英文别名: N-(p-bromobenzoyl)-O-benzylhydroxylamine；N-(benzyloxy)-4-bromobenzamide；4-bromo-N-phenylmethoxybenzamide
• 化学式: C₁₄H₁₂BrNO₂
• mdl: MFCD13526265
• 分子量: 306.159
• InChiKey: MQJLBFUTXICIQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzyl-O-(4-bromobenzoyl)hydroxylamine 在 叔丁基过氧化氢 、 四(三苯基膦)钯 、 palladium diacetate 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 24.0h， 生成 2-(benzyloxy)-5-(3,5-dimethylisoxazol-4-yl)-3-(4-fluorophenyl)-3-hydroxyisoindolin-1-one
  参考文献：
  名称：

  3-Hydroxyisoindolin-1-one derivates: Synthesis by palladium-catalyzed C H activation as BRD4 inhibitors against human acute myeloid leukemia (AML) cells

  摘要：

  Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family, which plays a key role in transcriptional regulation. Recent biological and pharmacological studies have enabled linking of the BET bromodomains with diseases, including inflammation and cancer, suggesting that bromodomains are druggable targets. In this study, we made further structural modifications of our previously reported BRD4 inhibitors, to develop new chemical scaffold 3-Hydroxyisoindolin-1-One. Then a series of compounds (10a-q) were synthesized via palladium-catalyzed C-H activation and BRD4-inhibitory activities and anti-proliferative effects of these compounds were evaluated. Compound 10e exhibited excellent BRD4-inhibitory activity with IC50 value of 80 nM and anti-proliferation potency with IC50 value of 365 nM in HL-60 (human promyelocytic leukemia) cancer cell lines. We have demonstrated compound 10e modulated the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 10e could be utilized as a BRD4 inhibitor for further leukemia treatment.

  DOI：

  10.1016/j.bioorg.2019.01.034
• 作为产物：
  描述：

  4-溴苯甲酸 在 草酰氯 、 sodium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 N-benzyl-O-(4-bromobenzoyl)hydroxylamine
  参考文献：
  名称：

  通过芳烃的插入无过渡金属合成N-芳基异羟肟酸

  摘要：

  描述了通过将芳烃插入N-烷氧基酰胺的NH键中的一种有效且无过渡金属的酰胺N-芳基化反应。发现各种反应性官能团，包括反应性醛羰基，呋喃环，碳-碳双键和吲哚的游离NH键均与该过程兼容。特别地，该方案可用于合成结构多样的N-芳基异羟肟酸酯和衍生自N-保护氨基酸和肽的异羟肟酸。在存在多个酰胺N–H键的情况下，N-芳基化反应可以在末端N -OBn酰胺的N–H键中选择性进行，从而产生所需的N-芳基异羟肟酸酯。

  DOI：

  10.1021/acs.joc.6b00111

文献信息

• Inhibition of Glyoxalase I: The First Low-Nanomolar Tight-Binding Inhibitors
  作者：Swati S. More、Robert Vince

  DOI：10.1021/jm900382u

  日期：2009.8.13

  -based glyoxalase I inhibitors culminated in the discovery of the first single-digit nanomolar inhibitor. This study makes available key information about possible means to address the issues of metabolic instability, low potency, and synthetic complexicity that have plagued the area of glyoxalase I inhibition. Knowledge garnered from this study has implications in the design of inhibitors with higher

  对已知的基于S-（N-芳基-N-羟基氨基甲酰基）谷胱甘肽的乙二醛酶I抑制剂的结构进行了一系列合理的修改，最终发现了第一个个位数的纳摩尔抑制剂。这项研究提供了有关解决困扰乙二醛酶I抑制区域的代谢不稳定，药效低和合成复杂性问题的可能手段的关键信息。从这项研究中获得的知识对具有更高构象定义和更低肽特性的抑制剂的设计具有重要意义。
• Design, synthesis and utilization of a novel coupling reagent for the preparation of O-alkyl hydroxamic acids
  作者：Nagnnath D. Kokare、Rahul R. Nagawade、Vipul P. Rane、Devanand B. Shinde

  DOI：10.1016/j.tetlet.2007.04.058

  日期：2007.6

  An efficient novel reagent, phosphoric acid diethyl ester 2-phenyl-benzimidazol-1-yl ester, was designed, and synthesized and its applicability was demonstrated for the preparation of O-alkyl hydroxamic acids. The O-alkyl hydroxamic acids of N-protected amino acids were also synthesized. The enantiomeric purity of the synthesized compounds were measured using chiral HPLC and the degree of racemization

  设计合成了一种高效的新型试剂磷酸二乙酯2-苯基-苯并咪唑-1-基酯，证明了其在制备O-烷基异羟肟酸中的适用性。还合成了N-保护的氨基酸的O-烷基异羟肟酸。使用手性HPLC测量合成化合物的对映体纯度，发现外消旋度可忽略不计。
• Design, synthesis, and biological evaluation of aryl N-methoxyamide derivatives as GPR119 agonists
  作者：Yoon Kyung Jang、Kyu Myung Lee、Kwan-Young Jung、Seung Kyu Kang、Suvarna H. Pagire、Jun Mi Lee、Haushabhau S. Pagire、Kwang Rok Kim、Myung Ae Bae、Hohjai Lee、Sang Dal Rhee、Jin Hee Ahn

  DOI：10.1016/j.bmcl.2017.06.032

  日期：2017.8

  A series of N-methoxyamide derivatives was identified and evaluated as GPR119 agonists. Several N-methoxyamides with thienopyrimidine and pyridine scaffolds showed potent GPR119 agonistic activities. Among them, compound 9c displayed good in vitro activity and potency. Moreover, compound 9c lowered glucose excursion in mice in an oral glucose tolerance test and increased GLP-1 secretion in intestinal

  鉴定出一系列N-甲氧基酰胺衍生物，并将其评估为GPR119激动剂。几种带有噻吩并嘧啶和吡啶骨架的N-甲氧基酰胺显示出强效的GPR119激动活性。其中，化合物9c表现出良好的体外活性和效力。此外，化合物9c在口服葡萄糖耐量试验中降低了小鼠的葡萄糖偏移，并增加了肠道细胞中的GLP-1分泌。
• A Cascade Dehydrogenative Cross-Coupling/Annulation Reaction of Benzamides with β-Keto Esters for the Synthesis of Isoquinolinone Derivatives
  作者：Guo-Dong Xu、Zhi-Zhen Huang

  DOI：10.1021/acs.orglett.7b02978

  日期：2017.12.1

  A novel cascade DCC/annulation reaction of N-alkoxybenzamides with β-keto esters has been developed for the synthesis of isoquinolinone derivatives under palladium catalysis. A plausible mechanism involving α-C(sp2)–H activation and a Pd(II)/Pd(IV) catalytic cycle is also proposed.

  已经开发了新颖的N-烷氧基苯甲酰胺与β-酮酸酯的级联DCC /环化反应，用于在钯催化下合成异喹啉酮衍生物。还提出了一个可行的机制，涉及α-C（sp 2）–H活化和Pd（II）/ Pd（IV）催化循环。
• Visible-light-promoted N–H functionalization of O-substituted hydroxamic acid with diazo esters
  作者：Shuangshuang Xia、Yongchan Jian、Liwen Zhang、Cheng Zhang、Yuanyuan An、Yubin Wang

  DOI：10.1039/d3ra02407e

  日期：——

  Herein we report an N–H functionalization of O-substituted hydroxamic acid with diazo esters under blue LED irradiation conditions. The present transformations could be performed efficiently under mild conditions without use of catalyst, additive and N2 atmosphere. Interestingly, when THF and 1,4-dioxane were employed as the reaction solvents, an active oxonium ylide involved three-component reaction

  在此，我们报道了在蓝色 LED 照射条件下 O-取代异羟肟酸与重氮酯的 N-H 官能化。在不使用催化剂、添加剂和 N 2气氛的情况下，本转化可以在温和条件下有效地进行。有趣的是，当使用 THF 和 1,4-二恶烷作为反应溶剂时，活性氧鎓叶立德分别涉及三组分反应和卡宾物种向异羟肟酸酯中的 N-H 插入。