(E,E)-3,5-bis(2-fluorobenzylidene)-4-piperidone acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (E,E)-3,5-bis(2-fluorobenzylidene)-4-piperidone acetate
• 英文别名: 3,5-bis-(2-fluorobenzylidene)-piperidin-4-one, acetic acid salt；acetic acid;(3E,5E)-3,5-bis[(2-fluorophenyl)methylidene]piperidin-4-one
• 化学式: C₂H₄O₂*C₁₉H₁₅F₂NO
• 分子量: 371.384
• InChiKey: UWAXBUJMNNKCNQ-XETSTSIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E,E)-3,5-bis(2-fluorobenzylidene)-4-piperidone acetate 在 potassium carbonate 作用下， 生成 3,5-二[(2-氟苯基)亚甲基]-4-哌啶酮
  参考文献：
  名称：

  Synthesis and structural determination of 3,5-bis(2-fluorobenzylidene)-4-piperidone analogs of curcumin

  摘要：

  Analogs of cytotoxic compound 3,5-bis(2-fluorobenzylidene)-4-piperidone (1) were synthesized and their molecular structures were characterized by H-1, C-13 NMR, ESI-MS, IR spectra and X-ray crystallography. The central ring of the piperidin-4-one ring assumes a sofa conformation with two benzylidene rings connected through E, E oriented groups. The compound 1 crystallized in triclinic space group P (1) over bar. In order to obtain potentially more efficacious compounds, three dimers of 3,5-bis(2-fluorobenzylidene)-4-piperidone were synthesized. The two molecules of 1 were conjugated together via -N-oxalyl-N- (3), -N-fumaryl-N- (4) or -N-DTPA-N- (5) linkers. Compound 3 crystallized in monoclinic space group P2(1)/n. (C) 2009 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2009.07.016
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 溶剂黄146 、 2-氟苯甲醛 在 盐酸 作用下， 反应 48.0h， 以94%的产率得到(E,E)-3,5-bis(2-fluorobenzylidene)-4-piperidone acetate
  参考文献：
  名称：

  Synthesis and structural determination of 3,5-bis(2-fluorobenzylidene)-4-piperidone analogs of curcumin

  摘要：

  Analogs of cytotoxic compound 3,5-bis(2-fluorobenzylidene)-4-piperidone (1) were synthesized and their molecular structures were characterized by H-1, C-13 NMR, ESI-MS, IR spectra and X-ray crystallography. The central ring of the piperidin-4-one ring assumes a sofa conformation with two benzylidene rings connected through E, E oriented groups. The compound 1 crystallized in triclinic space group P (1) over bar. In order to obtain potentially more efficacious compounds, three dimers of 3,5-bis(2-fluorobenzylidene)-4-piperidone were synthesized. The two molecules of 1 were conjugated together via -N-oxalyl-N- (3), -N-fumaryl-N- (4) or -N-DTPA-N- (5) linkers. Compound 3 crystallized in monoclinic space group P2(1)/n. (C) 2009 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2009.07.016

文献信息

• Curcumin analogs with anti-tumor and anti-angiogenic properties
  申请人：——

  公开号：US20020019382A1

  公开（公告）日：2002-02-14

  The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及表现出抗肿瘤和抗血管生成特性的姜黄素类似物，包括这些化合物的药物配方以及使用这些化合物的方法。
• [EN] CURCUMIN ANALOGUES FOR TREATING CANCER<br/>[FR] ANALOGUES DE CIRCUMINE DESTINES AU TRAITEMENT DU CANCER
  申请人：UNIV EMORY

  公开号：WO2001040188A1

  公开（公告）日：2001-06-07

  The present invention is directed to curcumin analogs (I), wherein Y is OH, halogen, or CF3; Z is H, OH, OR1, halogen, or CF3; X1 and X2 are independently C or N; and A is as defined in the application; exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及姜黄素类似物(I)，其中Y为OH、卤素或CF3；Z为H、OH、OR1、卤素或CF3；X1和X2独立地为C或N；A如本申请所定义；该类似物具有抗肿瘤和抗血管生成作用，制备包括这些化合物的制药组合物以及使用这些化合物的方法。
• CURCUMIN ANALOGS WITH ANTI-TUMOR AND ANTI-ANGIOGENIC PROPERTIES
  申请人：Snyder James P.

  公开号：US20080234320A1

  公开（公告）日：2008-09-25

  The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及展现抗肿瘤和抗血管生成特性的姜黄素类似物，包括这些化合物的制药配方和使用这些化合物的方法。
• Novel curcuminoid-factor VIIa constructs as suppressors of tumor growth and angiogenesis
  申请人：——

  公开号：US20040009914A1

  公开（公告）日：2004-01-15

  The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The present invention further provides for the synthesis of novel curcuminoid-tether-linker-factor VIIa compositions and for methods of delivery of effective doses of the novel compositions to target tumor or endothelial cells in a patient

  氟化姜黄素（3,5-双-(2-氟亚苄基)-哌啶-4-酮-乙酸酯）抑制肿瘤细胞生长的效果是顺铂的十倍。本发明提供了专门向癌细胞和滋养实体瘤的血管内皮细胞递送细胞毒性化合物（如姜黄素）的方法。该方法包括将药物与一种蛋白质（如因子 VIIa）拴在一起，这种蛋白质对表面蛋白质组织因子具有高亲和力。复合后，产生的异二聚体被内吞，随后药物通过蛋白水解作用在靶细胞内释放。本发明进一步提供了新型姜黄素-系链-连接剂-因子 VIIa 组合物的合成方法，以及将有效剂量的新型组合物递送至患者体内靶肿瘤或内皮细胞的方法。
• Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents
  作者：Brian K. Adams、Eva M. Ferstl、Matthew C. Davis、Marike Herold、Serdar Kurtkaya、Richard F. Camalier、Melinda G. Hollingshead、Gurmeet Kaur、Edward A. Sausville、Frederick R. Rickles、James P. Snyder、Dennis C. Liotta、Mamoru Shoji

  DOI：10.1016/j.bmc.2004.05.006

  日期：2004.7

  A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI). These compounds are symmetrical alpha,beta-unsaturated and saturated ketones. The majority of the analogs demonstrated a moderate degree of anti-cancer activity. Compounds 10, 11, and 14 exhibited a high degree of cytotoxicity in the NCI in vitro anti-cancer cell line screen. In addition, this screen revealed that these compounds inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. In independent in vitro screens conducted at Emory, the same compounds plus 4, 5, 8, 9, and 13 exhibited a high degree of cytotoxicity to tumor cells. Analogs that were effective in the anti-cancer screens were also effective in in vitro anti-angiogenesis assays. Compounds 4, 9, 11, and 14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound 14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials. Based on the favorable in vitro anti-cancer and anti-angiogenesis results with 14, further in vivo tests were conducted. This compound effectively reduced the size of human breast tumors grown in female athymic nude mice and showed little toxicity. This data, coupled with the remarkable in vitro data, suggests that compound 14 may potentially be an effective chemotherapeutic agent. As a follow-up, a 3D quantitative structure relationship based on 14 has been developed. It shows a cross-validated r(2)(q(2)) = 0.83 and a predictive r(2)(p(2)) = 0.71. COMPARE analysis suggests the compound to be a possible RNA/DNA antimetabolite, but also implies that the compound's cytotoxicity may arise from a presently unknown mechanism. (C) 2004 Elsevier Ltd. All rights reserved.