2-(m-Tolyl)-4-phenylmethylen-2-oxazolin-5-on | 42344-21-8

• 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-(m-Tolyl)-4-phenylmethylen-2-oxazolin-5-on
• 英文别名: 4-benzylidene-2-m-tolyl-4H-oxazol-5-one；4-Benzylidene-2-(3-methylphenyl)-1,3-oxazol-5-one
• CAS: 42344-21-8
• 化学式: C₁₇H₁₃NO₂
• mdl: MFCD00502446
• 分子量: 263.296
• InChiKey: MQVCGLGNTGQZAK-UHFFFAOYSA-N

物化性质

• 沸点：
  407.6±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(m-Tolyl)-4-phenylmethylen-2-oxazolin-5-on 在 溴 、 calcium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication

  摘要：

  A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti‐hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D‐QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (Sө) increase the anti‐HBV activities of the arylpropenamide molecules. Predictive 3D‐QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross‐validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

  DOI：

  10.1111/cbdd.12774
• 作为产物：
  描述：

  间甲基苯甲酸 在 氯化亚砜 、 potassium acetate 、 乙酸酐 、 sodium hydroxide 作用下， 反应 5.5h， 生成 2-(m-Tolyl)-4-phenylmethylen-2-oxazolin-5-on
  参考文献：
  名称：

  Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication

  摘要：

  A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti‐hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D‐QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (Sө) increase the anti‐HBV activities of the arylpropenamide molecules. Predictive 3D‐QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross‐validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

  DOI：

  10.1111/cbdd.12774

文献信息

• Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents
  作者：Xiaoke Gu、Yinpeng Zhang、Yueting Zou、Xin Li、Mingyu Guan、Qingqing Zhou、Jingying Qiu

  DOI：10.1016/j.bmc.2020.115892

  日期：2021.1

  As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value

  作为我们先前工作的延续，设计并合成了一系列新的苯基丙烯酰胺衍生物（4Aa-g，4Ba-t，5和6a-c）作为非核苷类抗HBV剂。其中，化合物4Bs可以有效抑制野生型和拉米夫定（3TC）/恩替卡韦耐药HBV突变株中HBV DNA复制，IC 50值分别为0.19和0.18μM。值得注意的是，4Bs的选择性指数值高于526，表明安全性良好。有趣的是，不像核苷类似物3TC，4BS能显著禁止3.5kb的pgRNA表达。分子对接研究表明4B通过疏水，π-π和H键相互作用可以很好地适合HBV核心蛋白的二聚体-二聚体界面。考虑到强效的抗HBV活性，低毒性以及与核苷类抗HBV药物3TC不同的抗HBV机理，化合物4Bs有望成为开发新型非核苷类抗HBV治疗药物的有希望的线索，并值得进一步研究。
• Discovery of Novel Pyrazolo-pyridone DCN1 Inhibitors Controlling Cullin Neddylation
  作者：Ho Shin Kim、Jared T. Hammill、Daniel C. Scott、Yizhe Chen、Jaeki Min、Jonah Rector、Bhuvanesh Singh、Brenda A. Schulman、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.9b00410

  日期：2019.9.26

  Chemical control of cullin neddylation is attracting increased attention based largely on the successes of the NEDD8-activating enzyme (E1) inhibitor pevonedistat. Recently reported chemical probes enable selective and time-dependent inhibition of downstream members of the neddylation trienzymatic cascade including the co-E3, DCN1. In this work, we report the optimization of a novel class of small molecule inhibitors of the DCN1-UBE2M interaction. Rational X-ray co-structure enabled optimization afforded a 2S-fold improvement in potency relative to the initial screening hit. The potency gains are largely attributed to additional hydrophobic interactions mimicking the N-terminal acetyl group that drives binding of UBE2M to DCN1. The compounds inhibit the protein-protein interaction, block NEDD8 transfer in biochemical assays, engage DCN1 in cells, and selectively reduce the steady-state neddylation of Cul1 and Cul3 in two squamous carcinoma cell lines harboring DCN1 amplification.
• Islam,A.M. et al., Australian Journal of Chemistry, 1973, vol. 26, p. 1701 - 1704
  作者：Islam,A.M. et al.

  DOI：——

  日期：——