2-phenyl-4-(cinnamylidene)-2-oxazolin-5-one | 5438-08-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-phenyl-4-(cinnamylidene)-2-oxazolin-5-one
• 英文别名: 2-Phenyl-4-cinnamyliden-oxazolon-5；4-Cinnamyliden-2-phenyl-oxazolon-(5)；2-phenyl-4-(3-phenyl-allylidene)-4H-oxazol-5-one；4-Cinnamyliden-2-phenyl-4H-oxazol-5-on；4-Cinnamylidene-2-phenyl-1,3-oxazol-5-one
• CAS: 5438-08-4
• 化学式: C₁₈H₁₃NO₂
• mdl: MFCD00030561
• 分子量: 275.307
• InChiKey: AYHSMADDXZUZBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-phenyl-4-(cinnamylidene)-2-oxazolin-5-one 在 盐酸 、 水 、 sodium methylate 、 氢化钾 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 4-Methoxy-5-[(E)-3-phenyl-prop-2-en-(E)-ylidene]-1,5-dihydro-pyrrol-2-one
  参考文献：
  名称：

  Stachel, Hans-Dietrich; Harigel, K. Klaus; Poschenrieder, Hermann, Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1195 - 1199

  摘要：

  DOI：
• 作为产物：
  描述：

  2-benzoylamino-5-phenyl-penta-2,4-dienoic acid 在 乙酸酐 作用下， 生成 2-phenyl-4-(cinnamylidene)-2-oxazolin-5-one
  参考文献：
  名称：

  Erlenmeyer; Matter, Justus Liebigs Annalen der Chemie, 1904, vol. 337, p. 273

  摘要：

  DOI：

文献信息

• Base Induced Condensation of Malononitrile with Erlenmeyer Azlactones: An Unexpected Synthesis of Multi‐Substituted Δ ² ‐Pyrrolines and Their Cytotoxicity
  作者：Seegehalli M. Anil、Muddenahalli S. Sudhanva、Toreshettahally R. Swaroop、Ajjampura C. Vinayaka、Narasimhamurthy Rajeev、Kuppalli R. Kiran、Rangappa Shobith、Maralinganadoddi P. Sadashiva

  DOI：10.1002/cbdv.202000014

  日期：2020.5

  synthesized products were screened for cytotoxic properties on different cancer cell lines such as A549 (Human lung adenocarcinoma cells), HeLa (Human cervical adenocarcinoma cells), Jurkat (Human chronic myeloid leukemia cells) and K562 (Human leukemic T cell Lymphoblast cells). Among the synthesized library of compounds, 6f and 6q displayed potent cytotoxic activity.

  开发了一种有效的、无金属的方法，通过 1,2 加成使丙二腈与 Erlenmeyer azlactones 的弱碱催化环缩合反应来合成多取代的 Δ2-吡咯啉衍生物。该反应的模块化用于组装一系列多取代吡咯啉。此外，还筛选了合成产品对 A549（人肺腺癌细胞）、HeLa（人宫颈腺癌细胞）、Jurkat（人慢性粒细胞白血病细胞）和 K562（人白血病 T 细胞淋巴母细胞）等不同癌细胞系的细胞毒性特性。 . 在合成的化合物库中，6f 和 6q 显示出强大的细胞毒活性。
• Sonochemical Hot-spot Assisted One-pot Synthesis of 4-arylmethylidene - 2-phenyl-4H-oxazol-5-ones Using Nano-MgO as an Efficient Catalyst
  作者：Sadeq Hamood Saleh Azzam、G. T. Chandrappa、Mohamed Afzal Pasha

  DOI：10.2174/1570178611310040010

  日期：2013.5.1

  Twelve 4-arylmethylidene-2-phenyl-4H-oxazol-5-ones were prepared in excellent yield by sonicating a mixture of an araldehyde, hippuric acid and acetic anhydride in the presence of a green heterogeneous NanoMgO as a basic catalyst. The catalytic activity of NanoMgO was found to be higher compared with bulk MgO powder under the same conditions. This method provides several advantages such as short reaction time, high yields, cleaner reaction condition, involves simple and easy workup procedure makes this protocol economically viable.

  十二种4-芳基亚甲基-2-苯基-4H-噁唑-5-酮在超声波作用下，通过将芳醛、氨基苯甲酸和醋酸酐的混合物与绿色的非均相NanoMgO作为碱催化剂反应，以优异的产率制备而成。在相同条件下，NanoMgO的催化活性高于块状MgO粉末。该方法具有多个优点，如反应时间短、产率高、反应条件更干净，以及操作简单易行，使得该方案在经济上可行。
• Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice
  作者：Sara R. Oliveira、Pedro A. Dionísio、Maria M. Gaspar、Maria B. T. Ferreira、Catarina A. B. Rodrigues、Rita G. Pereira、Mónica S. Estevão、Maria J. Perry、Rui Moreira、Carlos A. M. Afonso、Joana D. Amaral、Cecília M. P. Rodrigues

  DOI：10.3390/ijms22105289

  日期：——

  Parkinson’s disease (PD) is the second most common neurodegenerative disorder, mainly characterized by motor deficits correlated with progressive dopaminergic neuronal loss in the substantia nigra pars compacta (SN). Necroptosis is a caspase-independent form of regulated cell death mediated by the concerted action of receptor-interacting protein 3 (RIP3) and the pseudokinase mixed lineage domain-like protein (MLKL). It is also usually dependent on RIP1 kinase activity, influenced by further cellular clues. Importantly, necroptosis appears to be strongly linked to several neurodegenerative diseases, including PD. Here, we aimed at identifying novel chemical inhibitors of necroptosis in a PD-mimicking model, by conducting a two-step screening. Firstly, we phenotypically screened a library of 31 small molecules using a cellular model of necroptosis and, thereafter, the hit compound effect was validated in vivo in a sub-acute 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) PD-related mouse model. From the initial compounds, we identified one hit—Oxa12—that strongly inhibited necroptosis induced by the pan-caspase inhibitor zVAD-fmk in the BV2 murine microglia cell line. More importantly, mice exposed to MPTP and further treated with Oxa12 showed protection against MPTP-induced dopaminergic neuronal loss in the SN and striatum. In conclusion, we identified Oxa12 as a hit compound that represents a new chemotype to tackle necroptosis. Oxa12 displays in vivo effects, making this compound a drug candidate for further optimization to attenuate PD pathogenesis.

  帕金森病（PD）是第二常见的神经退行性疾病，主要特征是与黑质致密部（SN）中进行性多巴胺能神经元丧失相关的运动缺陷。坏死凋亡是一种受调控的细胞死亡形式，不依赖半胱氨酸蛋白酶的介导，由受体相互作用蛋白3（RIP3）和伪激酶混合谱系结构域类蛋白（MLKL）协同作用介导。通常还依赖于RIP1激酶活性，并受进一步细胞信号的影响。重要的是，坏死凋亡似乎与包括PD在内的几种神经退行性疾病密切相关。在这里，我们旨在通过进行两步筛选，在模拟PD的模型中鉴定新的坏死凋亡化学抑制剂。首先，我们使用细胞模型对包含31种小分子的化合物库进行表型筛选，然后验证击中化合物在亚急性1-甲基-1-4-苯基-1,2,3,6-四氢吡啶盐酸盐（MPTP）PD相关小鼠模型中的体内效果。从最初的化合物中，我们确定了一个击中物—Oxa12，它强烈抑制了BV2小鼠微胶质细胞系中由泛半胱氨酸蛋白酶抑制剂zVAD-fmk诱导的坏死凋亡。更重要的是，暴露于MPTP并进一步接受Oxa12治疗的小鼠显示出对MPTP诱导的SN和纹状体中多巴胺能神经元丧失的保护作用。总之，我们确定了Oxa12作为一个击中化合物，代表了一种新的化学类型来对抗坏死凋亡。Oxa12在体内显示出效果，使得这种化合物成为进一步优化以减轻PD发病机制的药物候选化合物。
• Amphiphilic allylation of arylidene-1,3-oxazol-5(4H)-one using bis-π-allylpalladium complexes: an approach to synthesis of cyclohexyl and cyclohexenyl α-amino acids
  作者：Afaf R. Genady、Hiroyuki Nakamura

  DOI：10.1039/c1ob05952a

  日期：——

  α-amino acids via palladium-catalyzed three-component assemblies followed by ring-closing metathesis (RCM) is described. The present catalytic reaction is successfully extended to substituted benzylidene azlactones 2a–j RCH=(1,3-oxazole): R = alkyl or aryl. The amphiphilic bis-allylation of these substrates has been achieved by replacing toxic allylstannanes with allyltrifluoroborate and the reaction

  一种有效的合成环己基和 环己烯基α-氨基通过酸 钯催化三组分组装，然后进行闭环复分解（RCM）。本催化反应成功地扩展到取代亚苄基内酯2a–j RCH =（1,3-恶唑）：R ＝烷基或芳基。这些底物的两亲性双烯丙基化已通过用三氟硼酸烯丙酯 反应顺利进行，得到相应的 1,7-二烯衍生品3a–j的收益率可以接受。使用第一代Grubbs催化剂得到的辛二烯的RCM可轻松获得立体定义的取代基环己烯高收率的7-11衍生物。酸水解恶唑酮7–10的环给出了受保护的氨基酸12–16。13和15的脱苯甲酰化分别以优异的产率提供了1-氨基-6-芳基-环己-3-烯羧酸17和18。此外，催化还原13得到相应的环己烷衍生物19可以去苯甲酰化得到1-氨基-2-苯基环己烯-1-羧酸（20）。通过X射线结构分析证实了化合物9、12和13的结构。这是产生大量环状α，α-二取代的极好方法α-氨基 酸。
• 5-Oxazolones. Part V. Reaction of 4-alkylidene-5(4h)-oxazolones with ethyl 3-oxo-4-triphenylphosphoranylidene-butyrate
  作者：Francesca Clerici、Elena Folpini、Maria L. Gelmi、Donato Pocar

  DOI：10.1016/s0040-4020(01)81003-6

  日期：1991.10

  The reaction of 4-alkylidene-5(4H)-oxazolones 2a-e with ethyl 3-oxo-4-triphenyphosphoranylidene-butyrate 1 affords dihydrobenzoxazoles 3a-c and the diastereoisomeric 1,3-cyclohexanedione ylides 4a-e and 5a-e. 3a is oxidized to the corresponding benzoxazoles 7a,b with iodine.

  4-亚烷基-5（4H）-恶唑酮2a-e与3-氧代-4-三苯并膦基亚丁基-丁酸酯1的反应得到二氢苯并恶唑3a-c和非对映异构体1，3-环己烷二酮基化物4a-e和5a-e。3a用碘氧化为相应的苯并恶唑7a，b。