3-(4-fluoro-benzyl)-pentane-2,4-dione | 791809-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-fluoro-benzyl)-pentane-2,4-dione
• 英文别名: 3-[(4-Fluorophenyl)methyl]pentane-2,4-dione
• CAS: 791809-56-8
• 化学式: C₁₂H₁₃FO₂
• 分子量: 208.232
• InChiKey: CEIGBPVBKJMMKP-UHFFFAOYSA-N

物化性质

• 沸点：
  290.6±25.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-fluoro-benzyl)-pentane-2,4-dione 在 sodium hydride 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 22.5h， 生成 4-[4-(4-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-1-yl]-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole derivatives as novel androgen receptor antagonists

  摘要：

  A series of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole compounds B were designed, synthesized, and evaluated for their potential as new-generation androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a bulky amide substituent (R-2) to the terminal aryl ring of the 4-arylmethyl group favored the reduction of agonistic activity and improved the pharmacokinetic (PK) properties. Similarly, introduction of a bulky substituent in the 4-aryloxy derivatives also resulted in improved PK properties. Compounds 28h and 44b exhibited potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft model. On the contrary, bicalutamide showed only partial suppression of tumor growth. These results suggest that the novel pyrazole derivatives are new-generation AR antagonists, different from the 'first-generation' antagonists such as bicalutamide in a CRPC treatment model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.005
• 作为产物：
  描述：

  4-氟溴苄 、 乙酰丙酮 在 sodium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.25h， 生成 3-(4-fluoro-benzyl)-pentane-2,4-dione
  参考文献：
  名称：

  Pd催化的不对称烯丙基取代级联取代4-羟基-2H-吡喃酮与内消旋烯丙基二碳酸酯

  摘要：

  开发了一种高效的 Pd 催化不对称烯丙基取代级联 4-羟基-2 H-吡喃酮与内消旋-烯丙基二碳酸酯合成动力学手性四氢-1 H-吡喃并[4,3 - b ]苯并呋喃-1-酮产品产率≤87%，ee≤99%。该协议是通过温度控制的动力学控制过程实现的，这已通过实验结果和控制实验进行了说明。该反应可以以克级进行，所得产物允许进行多种转化。

  DOI：

  10.1021/acs.orglett.2c00937

文献信息

• [EN] TRIAZINE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSES DE TRIAZINE ET LEUR UTILISATION
  申请人：NOVO PHARMACEUTICALS LTD DE

  公开号：WO2004096808A1

  公开（公告）日：2004-11-11

  A compound of formula (I) wherein R1 is hydrogen, alkyl, -alkyl-aryl, -alkyl-heterocycloalkyl or -alkyl-0-heterocycloalkyl; R2 is hydrogen, hydroxy, amino, nitro, alkoxy, alkyl, aryl or heteroaryl; R3 is hydrogen, alkyl or aryl; R4 is hydrogen, alkyl, aryl, heteroaryl, -CH(aryl)2, -alkyl-aryl or -C(0)0-alkyl; and R5 is alkyl, hydroxy or amino; or a pharmaceutically acceptable salt thereof; is new for use in therapy, e.g. in the treatment of Alzheimer's disease.

  式（I）的化合物中，其中R1是氢，烷基，-烷基-芳基，-烷基-杂环烷基或-烷基-0-杂环烷基；R2是氢，羟基，氨基，硝基，烷氧基，烷基，芳基或杂芳基；R3是氢，烷基或芳基；R4是氢，烷基，芳基，杂芳基，-CH（芳基）2，-烷基-芳基或-C（0）0-烷基；R5是烷基，羟基或氨基；或其药用可接受盐；用于治疗，例如用于治疗阿尔茨海默病。
• Discovery of small-molecule inhibitors of RUVBL1/2 ATPase
  作者：Gang Zhang、Feng Wang、Shan Li、Kai-Wen Cheng、Yingying Zhu、Ran Huo、Elyar Abdukirim、Guifeng Kang、Tsui-Fen Chou

  DOI：10.1016/j.bmc.2022.116726

  日期：2022.5

  relationship identified the benzyl group on R2 and aromatic ring-substituted piperazinyl on R4 as essential for inhibitory activity against the RUVBL1/2 complex. Of these, compound 18, which has IC50 values of 6.0 ± 0.6 μM and 7.7 ± 0.9 μM against RUVBL1/2 complex and RUVBL1 respectively, showed the most potent inhibition in cell lines A549, H1795, HCT116, and MDA-MB-231 with IC50 values of 15 ± 1.2 μM, 15 ± 1

  RUVBL1 和 RUVBL2 是高度保守的 AAA ATP 酶（与各种细胞活动相关的 ATP 酶）并且与癌症的进展高度相关，这使它们成为新型治疗性抗癌药物的有吸引力的靶标。在这项工作中，进行了基于对接的虚拟筛选以识别对 RUVBL1/2 复合物具有活性的化合物。七种化合物在酶促和细胞测定中均显示出对该复合物的抑制活性。基于化合物15的支架合成了一系列吡唑并[1,5- a ]嘧啶-3-甲酰胺类似物，具有抑制活性和良好的结构操作潜力。构效关系分析确定了 R 2上的苄基R 4上的芳环取代哌嗪基对 RUVBL1/2 复合物的抑制活性至关重要。其中，化合物18对 RUVBL1/2 复合物和 RUVBL1的 IC 50值分别为 6.0 ± 0.6 μM 和 7.7 ± 0.9 μM，在细胞系 A549、H1795、HCT116 和 MDA-MB-231 中表现出最有效的抑制作用IC 50值分别为 15
• 10.1021/acs.joc.4c00511
  作者：Dong, Qing、Yang, Yu-Huan、Lv, Xue-Jiao、Liu, Jia-Hui、Liu, Yan-Kai

  DOI：10.1021/acs.joc.4c00511

  日期：——

  An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration

  为了方便地获得 2,3-二烷基-5-羟基苯并呋喃，我们探索了一种经济的一锅三步反应序列，由容易获得的 2-单取代 1,3-二酮和 1,4-苯醌组成。通过使用廉价的 K 2 CO 3和浓缩物。以HCl为反应促进剂，通过连续的迈克尔加成、芳构化、逆克莱森、脱酰化、半缩酮化和脱水等过程，反应在温和条件下顺利进行，实用性强。此外，在衍生化研究过程中观察到一个有趣的现象，其中二氢喹啉通过歧化过程分别转化为四氢喹啉和喹啉产物。
• Design, synthesis, and biological evaluation of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole derivatives as novel androgen receptor antagonists
  作者：Satoshi Yamamoto、Naoki Tomita、Yuri Suzuki、Tomohiko Suzaki、Tomohiro Kaku、Takahito Hara、Masuo Yamaoka、Naoyuki Kanzaki、Atsushi Hasuoka、Atsuo Baba、Mitsuhiro Ito

  DOI：10.1016/j.bmc.2012.02.005

  日期：2012.4

  A series of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole compounds B were designed, synthesized, and evaluated for their potential as new-generation androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a bulky amide substituent (R-2) to the terminal aryl ring of the 4-arylmethyl group favored the reduction of agonistic activity and improved the pharmacokinetic (PK) properties. Similarly, introduction of a bulky substituent in the 4-aryloxy derivatives also resulted in improved PK properties. Compounds 28h and 44b exhibited potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft model. On the contrary, bicalutamide showed only partial suppression of tumor growth. These results suggest that the novel pyrazole derivatives are new-generation AR antagonists, different from the 'first-generation' antagonists such as bicalutamide in a CRPC treatment model. (C) 2012 Elsevier Ltd. All rights reserved.
• Pd-Catalyzed Asymmetric Allylic Substitution Cascade of Substituted 4-Hydroxy-2<i>H</i>-pyrones with <i>meso</i>-Allyl Dicarbonates
  作者：Yan Zheng、Siqi Dong、Kai Xu、Delong Liu、Wanbin Zhang

  DOI：10.1021/acs.orglett.2c00937

  日期：2022.5.20

  An efficient Pd-catalyzed asymmetric allylic substitution cascade of 4-hydroxy-2H-pyrones with meso-allyl dicarbonates has been developed for the synthesis of kinetic chiral tetrahydro-1H-pyrano[4,3-b]benzofuran-1-one products in ≤87% yield and ≤99% ee. The protocol was achieved via a temperature-controlled kinetic control process, which has been illustrated by means of the experimental results and

  开发了一种高效的 Pd 催化不对称烯丙基取代级联 4-羟基-2 H-吡喃酮与内消旋-烯丙基二碳酸酯合成动力学手性四氢-1 H-吡喃并[4,3 - b ]苯并呋喃-1-酮产品产率≤87%，ee≤99%。该协议是通过温度控制的动力学控制过程实现的，这已通过实验结果和控制实验进行了说明。该反应可以以克级进行，所得产物允许进行多种转化。