4-(N,N-diphenylamino)-4-oxobutanoic acid | 77778-94-0

• 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-(N,N-diphenylamino)-4-oxobutanoic acid
• 英文别名: 3-(diphenylaminocarbonyl)propionic acid；N,N-diphenyl-succinamic acid；N,N-Diphenyl-succinamidsaeure；Bernsteinsaeure-mono-diphenylamid；4-(Diphenylamino)-4-oxobutanoic acid；4-oxo-4-(N-phenylanilino)butanoic acid
• CAS: 77778-94-0
• 化学式: C₁₆H₁₅NO₃
• mdl: MFCD01174855
• 分子量: 269.3
• InChiKey: RNLOQAOTFNQIHN-UHFFFAOYSA-N

物化性质

• 熔点：
  218 °C (decomp)
• 沸点：
  541.2±33.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(N,N-diphenylamino)-4-oxobutanoic acid 在 rhodium(II) acetate dimer 、 三乙胺 、 氯甲酸甲酯 作用下， 以 氯仿 为溶剂， 反应 0.5h， 生成 6-(N,N-diphenylamino)-2H-pyran-3(4H)-one
  参考文献：
  名称：

  A Novel Cycloaddition Reaction of α-Diazo-γ-amido Ketones Catalyzed by Rhodium(II) Acetate. Scope and Mechanistic Details of the Process

  摘要：

  alpha-Diazo ketones containing an amido group in the gamma-position have been found to undergo a novel rhodium(II)-catalyzed cycloaddition reaction. Intramolecular cyclization of the keto carbenoid onto the oxygen atom of the amide group generates a carbonyl ylide dipole as a transient species. This highly stabilized dipole does not readily undergo 1,3-dipolar cycloaddition but rather transfers a proton to produce a cyclic ketene N,O-acetal. The ketene acetal is unstable to moisture and upon standing is readily hydrolyzed to a gamma-keto delta-lactone and an amine. In the absence of any significant amount of water, the ketene N,O-acetal undergoes conjugate addition with the activated st-bond of the dipolarophile to give a zwitterion intermediate. The anionic portion of the zwitterion adds to the neighboring carbonyl group. This is followed by epoxide ring formation with charge dissipation leading to an amido-substituted spiro cyclopentyl epoxide. In certain cases a hydroxy lactone was also isolated and its formation can be attributed to the competitive hydrolysis of the zwitterionic intermediate. The Rh(II)-catalyzed reaction of the diazo ketoamide derived from N-benzylpiperidone with DMAD afforded two different types of cycloadducts. In addition to the spiro cyclopentyl epoxide, a product derived from trapping of the carbonyl ylide dipole was also obtained, thereby providing additional support for the proposed mechanism.

  DOI：

  10.1021/jo952078h
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以92%的产率得到4-(N,N-diphenylamino)-4-oxobutanoic acid
  参考文献：
  名称：

  Psychotropic derivatives of 5-phenyl-7-chloro-1,3-dihydro-1,4-benzodiazepin-2-one and contribution to the synthesis of its 5-(2-chlorophenyl) analogue

  摘要：

  将7-氯-5-苯基-1,3-二氢-1,4-苯二氮杂环己-2-酮（I）与2,5-二甲氧基苯乙酰溴和3-(4-苯基哌嗪基)丙基氯烷基化，得到了诺多西泮（III）和（IV）的N-取代衍生物；化合物（IV）表现出潜在催眠药物的特性。4-氯硝基苯与(2-氯苯基)乙腈在碱性氢氧化物甲醇溶液中反应，得到混合物，从中分离出以下化合物：5-氯-3-(2-氯苯基)-2,1-苯并异噁唑（VII）、O-甲氧基肟（X）、5-氯-2,3-双(2-氯苯基)吲哚（XI）、2-氯-4'-硝基苯基酮（XVII）和2-氯-9-氰基喹啉-N-氧化物（XX）。4-氯硝基苯与(2-氟苯基)乙腈进行类似反应，得到化合物XX作为主要产物；少量得到4-硝基苯甲醚、2-氟-4'-硝基苯基酮（XVIII）和2-氯喹啉-9-碳腈（XXIV）。化合物VII还原为氨基苯基酮衍生物V，经过邻苯二甲酰亚乙酸酰衍生物VI转化为氯代甲基二氮杂西泮II。

  DOI：

  10.1135/cccc19803593

文献信息

• Design, synthesis and biological evaluation of anilide (dicarboxylic acid) shikonin esters as antitumor agents through targeting PI3K/Akt/mTOR signaling pathway
  作者：Yingying Ma、Xiaorong Yang、Hongwei Han、Zhongling Wen、Minkai Yang、Yahan Zhang、Jiangyan Fu、Xuan Wang、Tongming Yin、Guihua Lu、Jinliang Qi、Hongyan Lin、Xiaoming Wang、Yonghua Yang

  DOI：10.1016/j.bioorg.2021.104872

  日期：2021.6

  In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results

  三阴性乳腺癌（TNBC）因其分化低、增殖快和远处转移率高而预后不良。PI3K/Akt/mTOR 作为细胞内信号通路在细胞增殖、迁移、侵袭、代谢和再生中起关键作用。在这项工作中，我们设计并合成了一系列针对 PI3K/Akt/mTOR 信号通路的苯胺（二羧酸）紫草素酯，并评估了它们的抗肿瘤作用。通过计算机辅助药物设计方法（CADD）的三轮筛选，我们初步获得了十六种新型苯胺（二羧酸）紫草素酯，并鉴定为优良化合物。CCK-8 测定结果表明化合物 M9 对 MDA-MB-231、A549 和 HeLa 细胞系表现出比紫草素（SK）更好的抗增殖活性，50 = 4.52 ± 0.28 μM；SK：IC 50= 7.62 ± 0.26 μM）。此外，M9的抗增殖活性优于紫杉醇。进一步的药理研究表明，M9 可以诱导 MDA-MB-231 细胞凋亡并在 G2/M 期阻滞细胞周期。M9 还通过抑制 Wnt/β-catenin
• Synthesis and 1H NMR titration study of 7-deoxycholic amide or cholane ionophores containing different ion-recognizing groups at C3 and C12
  作者：Hyunju Oh、Sang Keun Han、Byeong Hyo Kim

  DOI：10.1002/hc.21002

  日期：——

  Tweezer-type ionophores containing C3-carbamoylpropanamidoacetoxy and C12-dithiocarbamoyl groups on a 7-deoxycholic amide or cholane derivative were designed and synthesized. A representative 1H NMR titration study indicated that newly synthesized ionophores form 1:1 complexes with the Ca2 + ion. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:187–194, 2012; View this article online at wileyonlinelibrary

  设计并合成了含有 C3-氨基甲酰丙酰胺乙酰氧基和 C12-二硫代氨基甲酰基在 7-脱氧胆酰胺或胆烷衍生物上的镊子型离子载体。代表性的 1H NMR 滴定研究表明，新合成的离子载体与 Ca2+ 离子形成 1:1 的复合物。© 2012 Wiley Periodicals, Inc. 杂原子化学 23:187–194, 2012; 在 wileyonlinelibrary.com 上在线查看这篇文章。DOI 10.1002/hc.21002
• Piutti, Gazzetta Chimica Italiana, 1884, vol. 14, p. 473
  作者：Piutti

  DOI：——

  日期：——
• Auwers, Justus Liebigs Annalen der Chemie, 1896, vol. 292, p. 185
  作者：Auwers

  DOI：——

  日期：——
• VEJDELEK Z.; RAJSNER M.; DLABAC A.; RYSKA M.; HOLUBEK J.; SVATEK E.; PROT+, COLLECT. CZECH. CHEM. COMMUN., 1980, 45, NO 12, 3593-3615
  作者：VEJDELEK Z.、 RAJSNER M.、 DLABAC A.、 RYSKA M.、 HOLUBEK J.、 SVATEK E.、 PROT+

  DOI：——

  日期：——