1-hydroxy-4-methyl-6-phenylpyridin-2(1H)-one | 50405-77-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-hydroxy-4-methyl-6-phenylpyridin-2(1H)-one
• 英文别名: 6-phenyl-4-methyl-1-hydroxypyridin-2(1H)-one；1-hydroxy-4-methyl-6-phenylpyridin-2-one
• CAS: 50405-77-1
• 化学式: C₁₂H₁₁NO₂
• 分子量: 201.225
• InChiKey: FKBGNOWCADYGTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3,3-二甲基丙烯酸甲酯 在 吡啶 、 aluminum (III) chloride 、 硫酸 、 盐酸羟胺 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 22.5h， 生成 1-hydroxy-4-methyl-6-phenylpyridin-2(1H)-one
  参考文献：
  名称：

  Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents

  摘要：

  Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress -induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11.01a possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11.01a significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11.01a is identified in our research as a prospective prototype in the innovation of stroke treatment.

  DOI：

  10.1021/acs.jmedchem.9b01338

文献信息

• Discovery of a novel series of N -hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality
  作者：Sarbjit Singh、Ja-Il Goo、Hyojin Noh、Sung Jae Lee、Myoung Woo Kim、Hyejun Park、Hitesh B. Jalani、Kyeong Lee、Chunsook Kim、Won-Ki Kim、Chung Ju、Yongseok Choi

  DOI：10.1016/j.bmc.2016.12.052

  日期：2017.2

  Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives. Mitochondrial activity assay showed that N-hydroxypyridone derivatives with biphenyl group have comparable to better protective effects than ciclopirox in astrocytes exposed to H2O2. N-hydroxypyridone derivatives, especially 11g, inhibited membrane-induced deterioration of mitochondrial membrane potential and oxygen consumption rate, and significantly improved cell viability of astrocytes. The results indicate that the N-hydroxypyridone motif can provide a novel cytoprotective scaffold for astrocytes via enhancing mitochondrial functionality. (C) 2017 Elsevier Ltd. All rights reserved.
• Lohaus; Dittmar, Arzneimittel-Forschung/Drug Research, 1981, vol. 31, # 8 a, p. 1311 - 1316
  作者：Lohaus、Dittmar

  DOI：——

  日期：——
• Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase
  作者：Baisong Zheng、Yuan Yao、Zhen Liu、Lisheng Deng、Justin L. Anglin、Hong Jiang、B. V. Venkataram Prasad、Yongcheng Song

  DOI：10.1021/ml400036z

  日期：2013.6.13

  Mutations in isocitrate dehydrogenase (IDH), a key enzyme in the tricarboxylic acid cycle, have recently been found in similar to 75% glioma and similar to 20% acute myeloid leukemia. Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. Strong evidence has shown mutant IDH1 represents a novel target for this type of cancer. We found two 1-hydroxypyridin-2-one compounds that are potent inhibitors of R132H and R132C mutants with K-i values as low as 120 nM. These compounds exhibit >60-fold selectivity against wild-type IDH1 and can inhibit the production of D-2-hydroxyglutaric acid in IDH1 mutated cells, representing novel chemical Probes for cancer biology studies. We also report the first inhibitor-bound crystal structures of IDH1(R132H), showing these inhibitors have H-bond, electrostatic, and hydrophobic interactions with the mutant enzyme. Comparison with the substrate-bound IDH1 structures revealed the structural basis for the high enzyme selectivity of these compounds.
• US3972888A
  申请人：——

  公开号：US3972888A

  公开（公告）日：1976-08-03
• Development of Novel <i>N</i>-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents
  作者：Linghao Hu、Hongxuan Feng、Hongguang Zhang、Songda Yu、Qinyuan Zhao、Wei Wang、Fengxia Bao、Xun Ding、Jiajing Hu、Manjiong Wang、Yixiang Xu、Zengrui Wu、Xiaokang Li、Yun Tang、Fei Mao、Xiaoyan Chen、Haiyan Zhang、Jian Li

  DOI：10.1021/acs.jmedchem.9b01338

  日期：2020.2.13

  Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress -induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11.01a possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11.01a significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11.01a is identified in our research as a prospective prototype in the innovation of stroke treatment.