3-<3-(4-Fluorphenyl)-1-oxo-2-propenyl>-4-hydroxy-6-methyl-2H-pyran-2-on | 1006372-29-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-<3-(4-Fluorphenyl)-1-oxo-2-propenyl>-4-hydroxy-6-methyl-2H-pyran-2-on
• 英文别名: 3-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-4-hydroxy-6-methyl-2H-pyran-2-one；(E)-3-(3-(4-fluorophenyl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one；ACOi-74-12-16；3-[(2E)-3-(4-Fluorophenyl)prop-2-enoyl]-4-hydroxy-6-methyl-2H-pyran-2-one；3-[(E)-3-(4-fluorophenyl)prop-2-enoyl]-4-hydroxy-6-methylpyran-2-one
• CAS: 1006372-29-7
• 化学式: C₁₅H₁₁FO₄
• 分子量: 274.248
• InChiKey: YNHXGRPTMCUEPR-QPJJXVBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-<3-(4-Fluorphenyl)-1-oxo-2-propenyl>-4-hydroxy-6-methyl-2H-pyran-2-on 在 碘 作用下， 以 二甲基亚砜 为溶剂， 以56%的产率得到2-(4-fluoro)phenyl-7-methylpyrano[4,3-b]pyran-4,5[4H,5H]dione
  参考文献：
  名称：

  Prakash, Om; Kumar, Ajay; Singh, Shiv P., Journal of the Indian Chemical Society, 2003, vol. 80, # 11, p. 1035 - 1036

  摘要：

  DOI：
• 作为产物：
  描述：

  3-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-6-methyl-2-oxo-2H-pyran-4-yl difluoridoborate 在 水 、 sodium carbonate 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以55%的产率得到3-<3-(4-Fluorphenyl)-1-oxo-2-propenyl>-4-hydroxy-6-methyl-2H-pyran-2-on
  参考文献：
  名称：

  Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase Inhibitors

  摘要：

  HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV drug development. Its uniqueness to the virus and its critical role in the viral life cycle makes IN suitable for selective inhibition. The recent approval of Raltegravir (MK-0518) has created a surge in interest and great optimism in the field. In our ongoing IN drug design research, we herein report the discovery of substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate complexes as novel IN inhibitors. In many of these compounds, complexation with boron difluoride increased the potency and selectivity of IN inhibition. Compound 9 was most active with an IC50 value of 9 mu M and 3 mu M for 3'-processing and strand transfer inhibition, respectively. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.067

文献信息

• Synthesis of disubstituted 1,4-diazepines with affinity to GABAA-receptor subtypes
  作者：Briel, Detlef、Rudolph、Unverferth、Mann

  DOI：10.1691/ph.2010.0559

  日期：——

  A series of tetrahydro-1H-1,4-diazepines 4a–c, dihydro-1H-1,4-diazepine 5 and pyrido diazepines 8 and 10 was prepared. Originated form dehydroacetic acid (DHA) and aromatic aldehydes cinnamoyl compounds 3a–c were obtained and converted with ethylenediamine to give tetrahydro-1H-1,4-diazepines 4a–c. For the synthesis of pyrido[1,2-d][1,4]diazepines 8 and 10 a new snythetic approach is described. Compounds 4b and 5 were investigated concerning their affinity to different benzodiazepine receptor subtypes. The determined IC50 values for 5 are 1.5 μM and 1.1 μM at 10 μM respectively.

  制备了一系列四氢-1H-1,4-二氮杂萘4a–c、二氢-1H-1,4-二氮杂萘5以及吡啶二氮杂萘8和10。这些化合物源自去氢乙酸（DHA）和芳香醛，得到了肉桂酸酯化合物3a–c，并与乙二胺反应，生成了四氢-1H-1,4-二氮杂萘4a–c。关于吡啶[1,2-d][1,4]二氮杂萘8和10的合成，描述了一种新的合成方法。化合物4b和5的亲和力被研究了不同的苯二氮平受体亚型。对于5所测得的IC50值分别为1.5 μM和1.1 μM（在10 μM的浓度下）。
• Synthesis and bioevaluation of a series of α-pyrone derivatives as potent activators of Nrf2/ARE pathway (part I)
  作者：Mei-yang Xi、Zhong-ying Sun、Hao-peng Sun、Jian-min Jia、Zheng-yu Jiang、Lei Tao、Ming Ye、Xi Yang、Ya-jing Wang、Xin Xue、Jing-jie Huang、Yuan Gao、Xiao-ke Guo、Sheng-lie Zhang、Ying-rui Yang、Qing-long Guo、Rong Hu、Qi-dong You

  DOI：10.1016/j.ejmech.2013.06.007

  日期：2013.8

  group exhibited the strongest ARE inductive activity in the first round structure–activity relationship (SAR) study. Biological studies showed the compound induced nuclear translocation of Nrf2 preceded by phosphorylation of ERK1/2. The data encouraged us to use 2 as lead and 20 derivatives were synthesized to discuss a more detailed SAR, leading to a more potent compound 9, which can be the starting

  当暴露于亲电子试剂中时，人结肠直肠癌细胞（HCT116）通过激活NF-E2相关因子2（Nrf2）/抗氧化反应元件（ARE）途径来抵消氧化应激。为了鉴定新的激活剂，荧光素酶报告基因检测被用于筛选我们实验室的内部数据库，从而导致了新型α-吡喃酮化合物1的成功。2与2-氟苯基组表现出在第一轮的结构-活性关系（SAR）研究最强是感性的活性。生物学研究表明，化合物诱导的Nrf2核易位，然后ERK1 / 2磷酸化。数据鼓励我们使用2作为前导物，并合成20个衍生物以讨论更详细的SAR，从而得到更有效的化合物9，可以作为进一步修饰的起始化合物。
• Charakterisierung polymorpher Modifikationen durch1H-NMR-Spektroskopie
  作者：Klaus Rehse、Wilhelm Schinkel

  DOI：10.1002/ardp.19833161109

  日期：——

  von zwanzig 4‐Hydroxy‐3‐(1‐oxo‐2‐propenyl)‐2‐pyronen werden mit Hilfe der 1H‐NMR‐Spektroskopie bei 250 MHz untersucht. Bei 17 Substanzen kann Polymorphie nachgewiesen werden, wobei bis zu vier Modifikationen aufgefunden werden. Es werden überwiegend und mit fast gleicher Häufigkeit Dimere von δ‐Truxinsäuretyp (Kopf‐Kopf‐Addition) und vom α‐Truxillsäuretyp (Kopf‐Schwanz‐Addition) gebildet.

  使用 1H NMR 光谱在 250 MHz 下研究了 20 个 4-羟基-3-(1-氧代-2-丙烯基)-2-吡喃酮的光环化产物。可在 17 种物质中检测到多态性，最多可发现四种修饰。δ-树莓酸类型（头对头添加）和α-树莓酸类型（头对尾添加）的二聚体主要形成，并且频率几乎相同。
• Discovery of PPARγ and glucocorticoid receptor dual agonists to promote the adiponectin and leptin biosynthesis in human bone marrow mesenchymal stem cells
  作者：Sungjin Ahn、Myunghwan Ahn、Suzie Park、Seungchan An、In Guk Park、Seok Young Hwang、Junpyo Gong、Soyeon Oh、Sun Hee Jin、Hee Jin Kim、Jae Hoon Cheong、Youngjoo Byun、Minsoo Noh

  DOI：10.1016/j.ejmech.2022.114927

  日期：2023.1

  Using the compound 1 structure, the structure-activity relationship study was performed to discover more potent compounds stimulating both adiponectin and leptin production. (E)-3-(3-(2-fluoropyridin-4-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one (11) exhibited the most potent adiponectin (EC50, 2.87 μM) and leptin (EC50, 2.82 μM) biosynthesis-stimulating activities in hBM-MSCs. In a target identification

  脂联素和瘦素是控制脂肪组织和其他器官系统之间串扰的主要脂肪细胞因子。低脂联素血症和低瘦素血症与人类代谢疾病有关。具有脂肪细胞因子生物合成刺激活性的化合物可以开发为针对不同代谢条件的治疗剂。在人骨髓间充质干细胞 (hBM-MSCs) 的表型筛选中，( E )-4-hydroxy-3-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)-6-methyl-2 H -pyran- 2-one ( 1 ) 被鉴定为在脂肪形成过程中增加脂联素生物合成，同时刺激瘦素的产生。使用化合物1结构，进行构效关系研究以发现更有效的化合物刺激脂联素和瘦素的产生。( E )-3-(3-(2-fluoropyridin-4-yl)acryloyl)-4-hydroxy-6-methyl-2 H -pyran-2-one ( 11 ) 表现出最有效的脂联素 (EC 50 , 2.87 μM) 和瘦素
• Discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiazepines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay
  作者：John Drewe、Shailaja Kasibhatla、Ben Tseng、Emma Shelton、David Sperandio、Robert M. Yee、Joane Litvak、Martin Sendzik、Jeffrey R. Spencer、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2007.05.098

  日期：2007.9

  We report the discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-methylphenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (2a) as an inducer of apoptosis using our proprietary cell- and caspase-based HTS assay. Through structure activity relationship (SAR) studies, 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(2-methoxy-4-(methylthio)phenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (5d) was identified as a potent apoptosis inducer with an EC50 value of 0.08 mu M in T47D cells, which was > 15-fold more potent than screening hit 2a. Compound 5d also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.05 mu M in T47D cells and to function as an inhibitor of tubulin polymerization. (c) 2007 Elsevier Ltd. All rights reserved.