phenyl (3-acetylphenyl)carbamate | 405905-06-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenyl (3-acetylphenyl)carbamate
• 英文别名: N-(3-acetylphenyl)-phenylcarbamate；Cambridge id 6943235；phenyl N-(3-acetylphenyl)carbamate
• CAS: 405905-06-8
• 化学式: C₁₅H₁₃NO₃
• mdl: MFCD00430563
• 分子量: 255.273
• InChiKey: VVPGDYGBBPJWFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.066
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl (3-acetylphenyl)carbamate 、 4-甲基苯硼酸酐 在 [Rh(OH)(cod)]2 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以83%的产率得到N-(3-acetylphenyl)-4-methylbenzamide
  参考文献：
  名称：

  铑催化的功能化封端异氰酸酯合成酰胺

  摘要：

  异氰酸酯是酰胺合成的有用组成部分，尽管它们的广泛使用受到其高反应性的限制，这通常导致较差的官能团耐受性和低聚倾向。在本文中，描述了铑催化的酰胺的合成，其将环硼氧烷与封闭的（被掩蔽的）异氰酸酯偶联。反应的成功取决于原位形成异氰酸酯和有机铑中间体的能力。依赖于掩蔽的异氰酸酯前体和有机铑中间体的高反应性，可实现宽泛的官能团耐受性，包括质子亲核基团（如胺，苯胺和醇）。

  DOI：

  10.1021/acscatal.9b02641
• 作为产物：
  描述：

  间氨基苯乙酮 、 氯甲酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 phenyl (3-acetylphenyl)carbamate
  参考文献：
  名称：

  Discovery of CC Chemokine Receptor-3 (CCR3) Antagonists with Picomolar Potency

  摘要：

  Starting with our previously described(20) class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase 1 clinical trials.

  DOI：

  10.1021/jm049530m

文献信息

• Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile, nonleaving group, and nucleofuge
  作者：Enrique A. Castro、María Cubillos、Rocío Iglesias、José G. Santos

  DOI：10.1002/kin.20700

  日期：2012.9

  (βN) in the range of 0.69–0.78 and 0.45–0.48, respectively, attributed to a concerted mechanism. The negative values found for the sensitivity of log kN to the basicity of the nonleaving (βnlg) and leaving (βlg) groups are discussed. Anilines are more reactive than isobasic SA amines, probably because of the greater steric hindrance offered by the latter. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet

  4-甲基苯基，苯基和4-氯苯基-2,4,6-三硝基苯碳酸酯（的反应的动力学1，2，和3，分别地）与一系列苯胺和仲脂环族（SA）的胺已经进行了用分光光度法在44重量％的乙醇-水，在25.0℃下，离子强度0.2 M的布朗斯台德图（统计学校正）为碳酸盐的反应中1 - 3与苯胺和SA胺是线性的与斜率（β ñ在的范围内）分别归因于协调机制，分别为0.69–0.78和0.45–0.48。对于log k N对非离开的碱性（βNLG）和离开（β LG）基团进行了讨论。苯胺比等压SA胺更具反应性，这可能是由于后者提供的更大的位阻。©2012 Wiley Periodicals，Inc.国际化学杂志Kinet 44：604–611，2012
• Anilinolysis of reactive aryl 2,4-dinitrophenyl carbonates: Kinetics and mechanism
  作者：Enrique A. Castro、Claudia Domecq、José G. Santos

  DOI：10.1002/kin.20544

  日期：2011.4

  at constant pH are linear, with slopes kN. The Brønsted plots (log kN vs. anilinium pKa) for the anilinolysis of 1–3 are linear, with slope (β) values of 0.52, 0.61, and 0.63, respectively. The values of these slopes and other considerations suggest that these reactions are ruled by a concerted mechanism. For these reactions, the kN values follow the reactivity sequence: 3 > 2 > 1. Namely, the reactivity

  一系列苯胺与碳酸2,4-二硝基苯基（1），4-硝基苯基2,4-二硝基苯基（2）和双（2,4-二硝基苯基）（3）碳酸酯的反应在在25.0±0.1°C时，乙醇-水为44 wt％，离子强度为0.2M。在胺下，获得了过量的拟一级反应速率系数（k obs）。的曲线ķ OBS针对在恒定pH游离胺的浓度是线性的，与斜坡ķ Ñ。苯胺分解1 – 3的布朗斯台德图（log k N vs.苯胺p K a）是线性的，斜率（β）值分别为0.52、0.61和0.63。这些斜率的值和其他考虑因素表明，这些反应是由协调机制决定的。对于这些反应，k N值遵循反应序列：3 > 2 > 1。即，反应性随着与非离去基团连接的硝基的数目增加而增加。与碳酸酯的逐步pyridinolysis这项工作的反应的比较1 - 3表明两性离子四面体中间体（T ±在吡啶分解反应中形成的α）通过等位苯胺基的吡啶部分的改变而不稳定。这归因于相对于等位吡啶，苯胺的T
• Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3
  作者：Yingxiu Li、Tianyu Ye、Le Xu、Yuhong Dong、Yong Luo、Chu Wang、Yufei Han、Ke Chen、Mingze Qin、Yajing Liu、Yanfang Zhao

  DOI：10.1016/j.ejmech.2019.111590

  日期：2019.11

  Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the "A" phenyl ring and "B" phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G(1)/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor. (C) 2019 Elsevier Masson SAS. All rights reserved.
• [EN] N-UREIDOALKYL-AMINO COMPOUNDS AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY<br/>[FR] COMPOSES DE N-UREIDOALKYL-AMINO EN TANT QUE MODULATEURS DE L'ACTIVITE DE RECEPTEURS DE LA CHIMIOKINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005048932A3

  公开（公告）日：2006-09-14
• Discovery of CC Chemokine Receptor-3 (CCR3) Antagonists with Picomolar Potency
  作者：George V. De Lucca、Ui Tae Kim、Brian J. Vargo、John V. Duncia、Joseph B. Santella、Daniel S. Gardner、Changsheng Zheng、Ann Liauw、Zhang Wang、George Emmett、Dean A. Wacker、Patricia K. Welch、Maryanne Covington、Nicole C. Stowell、Eric A. Wadman、Anuk M. Das、Paul Davies、Swamy Yeleswaram、Danielle M. Graden、Kimberly A. Solomon、Robert C. Newton、George L. Trainor、Carl P. Decicco、Soo. S. Ko

  DOI：10.1021/jm049530m

  日期：2005.3.1

  Starting with our previously described(20) class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase 1 clinical trials.