CNB-001 | 828911-76-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: CNB-001
• 英文别名: 1-phenyl-3,5-bis-2-(4-hydroxy-3-methoxystyryl)-1H-pyrazole；3,5-bis[β-(4-hydroxy-3-methoxyphenyl)ethenyl]-1-phenylpyrazole；4-[(1E)-2-{5-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-phenylpyrazol-3-yl}ethenyl]-2-methoxyphenol；4-[2-[5-[2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-phenylpyrazol-3-yl]ethenyl]-2-methoxyphenol
• CAS: 828911-76-8
• 化学式: C₂₇H₂₄N₂O₄
• 分子量: 440.499
• InChiKey: QUOCIDQIFWYHLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温下保存于惰性气体中

反应信息

• 作为产物：
  描述：

  乙酰丙酮 在 硼酸 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.36h， 生成 CNB-001
  参考文献：
  名称：

  姜黄素是钙/钙调蛋白依赖性蛋白激酶II的抑制剂

  摘要：

  钙/钙调蛋白依赖性蛋白激酶II（CaMKII）参与了高级大脑功能（如学习和记忆）的潜在机制。的CaMKII参与了病理谷氨酸也信令，因为它是由钙流入通过激活的Ñ甲基d天冬氨酸型谷氨酸受体（NMDAR）。在我们尝试鉴定CaMKII的植物调节剂时，我们观察到姜黄素（姜黄的组成部分及其类似物）会抑制Ca 2+依赖性和独立的CaMKII激酶活性。我们进一步报告姜黄素I，（3,5-双[β-（4-羟基-3-甲氧基苯基）乙烯基]吡唑）的杂环类似物，称为吡唑-姜黄素，比姜黄素是一种更有效的CaMKII抑制剂。还报道了微波辅助的姜黄素I及其杂环类似物的快速合成。

  DOI：

  10.1016/j.bmc.2012.08.029

文献信息

• Screening of curcumin-derived isoxazole, pyrazoles, and pyrimidines for their anti-inflammatory, antinociceptive, and cyclooxygenase-2 inhibition
  作者：Mahmood Ahmed、Muhammad Abdul Qadir、Abdul Hameed、Muhammad Imran、Muhammad Muddassar

  DOI：10.1111/cbdd.13076

  日期：2018.1

  against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental

  姜黄素已显示出针对各种疾病模型的不同表型的药理特性。已经采用了不同的合成途径来开发其众多衍生物，以发挥多种多样且改善的治疗作用。在这项研究中，我们合成了含有异恶唑，吡唑和嘧啶的姜黄素衍生物，然后在实验动物模型中评估了合成的分子的抗炎和镇痛活性。通过口服，在白化病小鼠中评估了合成分子的急性毒性。在10 mg / kg体重的剂量下观察到任何行为和神经学变化。此外，通过体外测定法进行了环氧合酶2（COX-2）酶抑制研究。体内抗炎研究表明姜黄素和嘧啶是最有效的抗炎剂，可将诱导的水肿从74.7％抑制到75.9％。化合物7，9，和12显示出相对较高的预防发作扭动比具有分别73.2％，74.9％，和71.8％，镇痛活性的任何其它化合物。这比双氯芬酸钠（参考药物，抑制67.1％）更好。同样，COX-2体外抑制试验结果表明，化合物12（抑制75.3％）是最有效的化合物。的分子对接研究10，11，和12中的人
• Puneeth, Honnalagere Ramesh; Chandrashekariah, Sharada Angatahally, International Journal of Pharmacy and Pharmaceutical Sciences, 2015, vol. 7, # 4, p. 244 - 249
  作者：Puneeth, Honnalagere Ramesh、Chandrashekariah, Sharada Angatahally

  DOI：——

  日期：——
• The inhibitory role of curcumin derivatives on AMPA receptor subunits and their effect on the gating biophysical properties
  作者：Mohammad Qneibi、Othman Hamed、Oswa Fares、Nidal Jaradat、Abdel-Razzak Natsheh、Qais AbuHasan、Nour Emwas、Rana Al-Kerm、Rola Al-Kerm

  DOI：10.1016/j.ejps.2019.06.005

  日期：2019.8

  Curcumin is a natural polyphenol that has a broad spectrum of therapeutic characters, including neuroprotective actions against various neurological diseases. However, the molecular mechanism behind its neuroprotective properties remains obscure. The current study investigated the neuroprotective properties of 7 different curcumin derivatives on the gating biophysical properties of AMPA receptors, specifically on the calcium-permeable homomeric GluA1 and calcium impermeable heteromeric GluA1/A2 subunits. Due to the association between excessive activation of AMPARs and neurotoxicity linked to numerous pathologies, we aim to target and manipulate the kinetics of AMPARs through these derivatives. The current study used patch-clamp electrophysiology to measure the whole-cell currents in the presence and absence of the curcumin derivatives onto HEK293 cells expressing AMPA subunits. Our results showed that some of the curcumin derivatives showed an inhibitory effect and altered the gating biophysical properties, namely, deactivation and desensitization. In the presence of those derivatives, the peak current measured was significantly reduced, and the desensitization and deactivation rates decreased as well, achieving slower kinetics of the receptor and depressing its activity. These results suggest that the two most promising derivatives have inhibitory actions and act as allosteric modulators. Many neurological diseases like epilepsy, ALS, and strokes are associated with overactivation of AMPA receptors. We can potentially synthesize a more potent neuroprotective drug to treat those neurological diseases, by understanding the most stable chemical interaction between the derivative and the receptor underlying the reported neuronal depressive properties.