1-((2,6-difluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine | 1186660-17-2

• 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: 1-((2,6-difluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine
• 英文别名: DASA-23；1-(2,6-difluorophenyl)sulfonyl-4-(4-methoxyphenyl)sulfonylpiperazine
• CAS: 1186660-17-2
• 化学式: C₁₇H₁₈F₂N₂O₅S₂
• 分子量: 432.469
• InChiKey: WRROVDDBUYSEPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl 4-((4-methoxyphenyl)sulfonyl)piperazine-1-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-((2,6-difluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine
  参考文献：
  名称：

  通过无创测量丙酮酸激酶M2成像肿瘤糖酵解的[18F] DASA-23的开发。

  摘要：

  目的癌症的一个特点是代谢重编程，癌细胞可以利用代谢重编程来确保快速生长和存活。丙酮酸激酶M2（PKM2）催化糖酵解的最后一步，这是肿瘤代谢和生长的关键步骤。最近，我们报道了第一个正电子发射断层扫描示踪剂的放射性合成，用于在体内可视化PKM2 ，即[ 11 C] DASA-23。由于在啮齿动物模型胶质母细胞瘤中用[ 11 C] DASA-23获得了非常有希望的成像结果，我们着眼于临床翻译的最终目标，着手生成这种示踪剂的F-18标记版本。在这里，我们报道了1-（（2-氟-6- [ 18 F]氟苯基）磺酰基）-4-（（4-甲氧基苯基）磺酰基）哌嗪（[ 18F] DASA-23）和我们对其在癌细胞中的结合特性的初步研究。 程序我们通过用K [ 18 F] F / K2将1-（（2-氟-6-硝基苯基）磺酰基）-4-（（4-甲氧基苯基）磺酰基）哌嗪（10）氟化合成了[ 18 F] DASA-23 .2

  DOI：

  10.1007/s11307-017-1068-8

文献信息

• IMAGING TUMOR GLYCOLYSIS BY NON-INVASIVE MEASUREMENT OF PYRUVATE KINASE M2
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20160158389A1

  公开（公告）日：2016-06-09

  A novel pyruvate kinase M2 (PKM2)-specific activator, [ 11 C]DASA-23 and derivatives thereof, and methods for their rapid synthesis are provided. The probes are particularly useful in methods for the non-invasive positron emission tomography (PET) detection and imaging of PKM2 expression in subcutaneous and orthotopic tumors. [ 11 C]DASA-23 cell uptake correlates with PKM2 protein expression in cultured tumor cells and orthotopic tumors are delineated from the surrounding normal brain tissue in vivo.

  提供了一种新型丙酮酸激酶M2（PKM2）特异性激活剂，[11C]DASA-23及其衍生物，以及它们的快速合成方法。这些探针在非侵入性正电子发射断层扫描（PET）检测和影像化亚表皮和原位肿瘤中PKM2表达的方法中特别有用。[11C]DASA-23的细胞摄取与培养肿瘤细胞中PKM2蛋白表达相关，并且在体内将原位肿瘤与周围正常脑组织分开。
• ACTIVATORS OF HUMAN PYRUVATE KINASE
  申请人：Thomas Craig J.

  公开号：US20120245141A1

  公开（公告）日：2012-09-27

  Disclosed are pyruvate kinase M2 activators, which are, bis sulfonamide piperazinyl compounds of Formula (I) and 2,4-disubstituted 4H-thieno[3,2-b]pyrrole-2-(substituted benzyl)pyridazin-3(2H)ones of Formula (II), wherein L and R 1 to R 16 are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer and anemia,

  本发明涉及丙酮酸激酶M2激活剂，其为式（I）的双磺酰胺哌嗪化合物和式（II）的2,4-二取代4H-噻吩[3,2-b]吡咯-2-(取代苄基)吡啶并[3(2H)]酮，其中L和R1至R16如本文所定义，可用于治疗许多可通过激活PKM2治疗的疾病，例如癌症和贫血。
• Imaging tumor glycolysis by non-invasive measurement of pyruvate kinase M2
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10039844B2

  公开（公告）日：2018-08-07

  A novel pyruvate kinase M2 (PKM2)-specific activator, [11C]DASA-23 and derivatives thereof, and methods for their rapid synthesis are provided. The probes are particularly useful in methods for the non-invasive positron emission tomography (PET) detection and imaging of PKM2 expression in subcutaneous and orthotopic tumors. [11C]DASA-23 cell uptake correlates with PKM2 protein expression in cultured tumor cells and orthotopic tumors are delineated from the surrounding normal brain tissue in vivo.

  本研究提供了一种新型丙酮酸激酶 M2（PKM2）特异性激活剂[11C]DASA-23 及其衍生物，以及快速合成它们的方法。这些探针特别适用于皮下和原位肿瘤中 PKM2 表达的无创正电子发射断层扫描（PET）检测和成像方法。[11C]DASA-23细胞摄取与培养肿瘤细胞中的PKM2蛋白表达相关，而且在体内可将原位肿瘤与周围正常脑组织区分开来。
• Evaluation of Substituted <i>N</i>,<i>N</i>′-Diarylsulfonamides as Activators of the Tumor Cell Specific M2 Isoform of Pyruvate Kinase
  作者：Matthew B. Boxer、Jian-kang Jiang、Matthew G. Vander Heiden、Min Shen、Amanda P. Skoumbourdis、Noel Southall、Henrike Veith、William Leister、Christopher P. Austin、Hee Won Park、James Inglese、Lewis C. Cantley、Douglas S. Auld、Craig J. Thomas

  DOI：10.1021/jm901577g

  日期：2010.2.11

  The metabolism of cancer cells is altered to support rapid proliferation. Pharmacological activators of a tumor cell specific pyruvate kinase isozyme (PKM2) may be an approach for altering the classic Warburg effect characteristic of aberrant metabolism in cancer cells yielding a novel anti proliferation strategy. In this manuscript, we detail the discovery of a series of Substituted N,N'-diarylsulfonamides as activators of PKM2. The synthesis of numerous analogues and the evaluation of structure-activity relationships are presented as well as assessments of mechanism and selectivity. Several agents are found that have good potencies and appropriate solubility for use as chemical probes of PKM2 including 55 (AC(50) = 43 nM, maximum response = 84%; solubility = 7.3 mu g/mL), 56 (AC(50) = 99 nM, maximum response 84%; solubility = 5.7 mu g/mL), and 58 (AC(50) = 38 nM, maximum response = 82%; solubility 51.2 mu g/mL). The small molecules described here represent first-in-class activators of PKM2
• PYRUVATE KINASE ACTIVATORS FOR USE FOR INCREASING LIFETIME OF THE RED BLOOD CELLS AND TREATING ANEMIA
  申请人：Agios Pharmaceuticals, Inc.

  公开号：EP2704719A1

  公开（公告）日：2014-03-12