1-Boc-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)piperazine | 1203494-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 1-Boc-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)piperazine
• 英文别名: tert-butyl 4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)piperazine-1-carboxylate
• CAS: 1203494-52-3
• 化学式: C₁₇H₂₄N₂O₆S
• 分子量: 384.453
• InChiKey: IHMDJBBPVFCFLA-UHFFFAOYSA-N

物化性质

• 沸点：
  517.4±60.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  93.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-Boc-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)piperazine 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-Boc-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)piperazine trifluoroacetate
  参考文献：
  名称：

  Evaluation of Substituted N,N′-Diarylsulfonamides as Activators of the Tumor Cell Specific M2 Isoform of Pyruvate Kinase

  摘要：

  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

  DOI：

  10.1021/jm901577g
• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二氧-6-磺酰氯 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以89%的产率得到1-Boc-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)piperazine
  参考文献：
  名称：

  Evaluation of Substituted N,N′-Diarylsulfonamides as Activators of the Tumor Cell Specific M2 Isoform of Pyruvate Kinase

  摘要：

  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

  DOI：

  10.1021/jm901577g

文献信息

• 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。
• Activators of the human pyruvate kinase M2 receptor
  申请人：Thomas Craig J.

  公开号：US08841305B2

  公开（公告）日：2014-09-23

  Disclosed are pyruvate kinase M2 activators, which are bis sulfonamide piperazinyl and piperidinyl compounds of Formula (I), 2,4-disubstituted 4H-thieno[3,2-c]pyrrole-2-(substituted benzyl)pyridazin-3(2H)-ones of Formula (II) and 6-(3,4-dimethylphenylaminosulfonyl)-3,4-dihydro-1H-quinolin-2-one of formula (III), wherein L, R1, R2, R11 to R16, R21 and R22 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）的双磺酰胺哌嗪基和哌啶基化合物，式（II）的2,4-二取代4H-噻吩[3,2-c]吡咯-2-（取代苯甲基）吡啶嗪-3（2H）-酮和式（III）的6-（3,4-二甲基苯胺基磺酰基）-3,4-二氢-1H-喹啉-2-酮，其中L，R1，R2，R11至R16，R21和R22如本文所定义，对于治疗通过激活PKM2可治疗的多种疾病，例如癌症和贫血，具有有用性。
• Activators of human pyruvate kinase
  申请人：Thomas Craig J.

  公开号：US08937067B2

  公开（公告）日：2015-01-20

  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 R1 to R16 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-(取代苯基)吡啶并[3(2H)]酮，其中L和R1到R16如本文所定义，对于通过激活PKM2可治疗的多种疾病，例如癌症和贫血具有治疗作用。
• [EN] ACTIVATORS OF HUMAN PYRUVATE KINASE<br/>[FR] ACTIVATEURS DE LA PYRUVATE KINASE HUMAINE
  申请人：US HEALTH

  公开号：WO2010042867A3

  公开（公告）日：2010-08-05
• US8841305B2
  申请人：——

  公开号：US8841305B2

  公开（公告）日：2014-09-23