2-phenyl-4-(2'-acetoxybenzal)oxazolone | 52900-70-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2-phenyl-4-(2'-acetoxybenzal)oxazolone
• 英文别名: 4-(2'-Acetoxy-benzyliden)-2-phenyl-oxazolin-5-on；4-((E)-2-acetoxy-benzylidene)-2-phenyl-4H-oxazol-5-one；[2-[(5-Oxo-2-phenyl-1,3-oxazol-4-ylidene)methyl]phenyl] acetate
• CAS: 52900-70-6
• 化学式: C₁₈H₁₃NO₄
• 分子量: 307.306
• InChiKey: CKVAALAFCQXIGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-phenyl-4-(2'-acetoxybenzal)oxazolone 在 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3-[3-{(5-chloro-1H-benzimidazole-2-yl)amino}propoxy]coumarin
  参考文献：
  名称：

  Inhibition of iNOS by Benzimidazole Derivatives: Synthesis, Docking, and Biological Evaluations

  摘要：

  背景：可诱导型一氧化氮合酶（iNOS）通过加速NO的产生在炎症性疾病的进展中发挥关键作用，因此，寻找开发选择性iNOS抑制剂的分子成为治疗复杂疾病炎症的有趣目标。 目的：本研究旨在通过计算机模拟和药理学研究设计、合成和评价苯并咪唑-香豆素偶联分子作为抗iNOS剂。 方法：对iNOS抑制剂的文献报告进行了关键研究，选择了（不）取代的香豆素核、2-氨基苯并咪唑和4原子连接器作为iNOS抑制的重要结构组成部分。设计并合成了两个系列的化合物（7-16和17-26）通过耦合这些组分。将这些化合物作为靶点进行iNOS（1QW4）和nNOS（1QW6）的对接。所有化合物均在体外评估了NO和iNOS的抑制活性。最终选定的化合物通过使用卡拉蓝诱导的大鼠爪水肿模型在体内评估其抗炎活性。 结果：所有化合物在体外显示出中等到良好的NO和iNOS抑制作用。化合物12是NO和iNOS最有效的抑制剂。因此，对其进行了毒性和抗炎活性评估。研究结果发现，它在急性毒性研究中是安全的，并且能够显著减少大鼠爪水肿。其抗炎行为类似于选择性iNOS抑制剂氨基胍。 结论：新合成的苯并咪唑-香豆素杂化物可能成为开发新型抗iNOS剂的潜在前导化合物。

  DOI：

  10.2174/1573406417666210927123137
• 作为产物：
  描述：

  C₃₆H₂₆N₂O₈Pd₂ 、 溶剂黄146 在 碘苯二乙酸 作用下， 反应 18.0h， 以56.5%的产率得到2-phenyl-4-(2'-acetoxybenzal)oxazolone
  参考文献：
  名称：

  Ortho-Palladation of (Z)-2-Aryl-4-Arylidene-5(4H)-Oxazolones. Structure and Functionalization

  摘要：

  Ortho-palladated complexes of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared through oxidative addition. The reaction of (Z)-2-phenyl-4-(2-bromobenzylidene)-5(4H)-oxazolone (4) with Pd-2(dba)(3)center dot CHCl3 gives the six-membered cyclopalladated dinuclear complex [Pd(mu-Br)(o-C6H4CH=CNC(O)OCPh)](2) (7). The reaction of 7 with PPh3 gives dinuclear 9, which incorporates one phosphine per Pd atom through cleavage of the Pd-N bond, and preserves the bromide bridging system. However, reaction with PPh2Me gives mononuclear 8, which incorporates two phosphines as a results of the cleavage of the mu-Br system and N displacement. In contrast, the reaction of 7 with pyridine gives complex 12 due to Simple cleavage of the Br bridge, leaving the N-bonding intact. Therefore, three different reaction pathways have been characterized. The reactivity of the Pd-C bond in 7 has also been examined, and functionalized oxazolones can be obtained. The reaction of 7 With PhI(OAc)(2) in acetic acid gives the starting oxazolone C6H4-2-Br-CH=CNC(O)OCPh (4), through the presumed oxidation of the Pd center and C-Br bond formation by reductive coupling. In contrast, the reaction of the acetate dimer 14 with PhI(OAc)(2) in acetic acid gives C6H4-2-OAc-CH=CNC(O)OCPh (20) through C-O coupling. When treatment of 7 with PhI(OAc)(2) is performed in MeOH or EtOH, the oxazolones C6H4-2-OR-CH=CNC(O)OCPh (R = Me (18), Et (19)) are obtained. The reaction of 7 with CO in alcohols ROH gives cleanly the oxazolones C6H4-2-CO2R-CH=CNC(O)OCPh (R = Me (21), Pr-i (22)) through CO migratory insertion into the Pd-C bond and further nucleophilic attack of the RO- fragment.

  DOI：

  10.1021/om901068f

文献信息

• Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as Immunosuppressants
  作者：Richa Minhas、Gulshan Bansal、Yogita Bansal

  DOI：10.2174/1573406415666190409111459

  日期：2020.5.20

  Nitric oxide (NO) is an important mediator in the pathogenesis and control of immune system-related disorders and its levels are modulated by inducible NO synthase (iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders. The present study aims at the development of coupled molecules via selection of pharmacophores for both immunomodulatory and antioxidant activities through iNOS inhibition.

  Variedly substituted coumarin moieties are coupled with naturally occurring phenols through an amide linkage and were predicted for activities using computer-based program PASS. The compounds predicted to have dual activities were synthesized. Docking studies were carried out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory and antioxidant activities.

  The synthesized compounds were found to be pure and were obtained in good yields. Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of NBT dye and showed maximum % iNOS inhibition. In DPPH assay, compound YR4e was observed as the most potent antioxidant (EC50 0.33 µM/mL). Based on these studies, compounds YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and lower HAT value of 3.5.

  Compound YR2e can be utilized as a pharmacological agent in the prevention or treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis, organ transplant and other autoimmune disorders.

  介绍：一氧化氮（NO）是免疫系统相关疾病发病和控制的重要介质，其水平受诱导型NO合酶（iNOS）调节。氧化应激是大多数自身免疫性疾病的另一个病理指标。本研究旨在通过选择对免疫调节和抗氧化活性均具有药效团的耦合分子的开发，通过iNOS抑制来实现。 方法：通过酰胺键将不同取代的香豆素基团与天然存在的酚偶联，并使用基于计算机的程序PASS预测其活性。合成了预测具有双重活性的化合物。进行了针对iNOS（PDB 1R35）的对接研究，评估了对接分数较高的化合物的免疫调节和抗氧化活性。 结果：合成的化合物纯度高，产率良好。具有最高对接得分（YR1a、YR2e、YR2c和YR4e）的化合物被选中用于体外模型评估。化合物YR2e和YR2c明显抑制了NBT染料的还原，并显示出最大的iNOS抑制率。在DPPH测定中，化合物YR4e被观察为最有效的抗氧化剂（EC50为0.33 μM/mL）。基于这些研究，化合物YR2e和YR2c被选择用于血凝试验。化合物YR2e被观察为最活跃的免疫抑制剂，具有最大的iNOS和NBT还原抑制能力，HAT值为3.5。 结论：化合物YR2e可以作为药理学试剂用于预防或治疗肿瘤、类风湿性关节炎、溃疡性结肠炎、器官移植和其他自身免疫性疾病。
• Karade; Shirodkar; Dhoot, Journal of Chemical Research, 2005, # 1, p. 46 - 47
  作者：Karade、Shirodkar、Dhoot、Waghmare

  DOI：——

  日期：——
• Khodaei, Mohammad Mehdi; Khosropour, Ahmad Reza; Jomor, Saied Jabar Hoseini, Journal of Chemical Research - Part S, 2003, # 10, p. 638 - 641
  作者：Khodaei, Mohammad Mehdi、Khosropour, Ahmad Reza、Jomor, Saied Jabar Hoseini

  DOI：——

  日期：——