1-(4-phenylpiperazin-1-yl)butane-1,3-dione | 2172-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-phenylpiperazin-1-yl)butane-1,3-dione
• 英文别名: 1-acetoacetyl-4-phenyl-piperazine
• CAS: 2172-83-0
• 化学式: C₁₄H₁₈N₂O₂
• mdl: MFCD01001291
• 分子量: 246.309
• InChiKey: QYHWWWNJUHBPKF-UHFFFAOYSA-N

物化性质

• 熔点：
  50-51 °C
• 沸点：
  435.2±40.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-dichlorobenzofuroxan 、 1-(4-phenylpiperazin-1-yl)butane-1,3-dione 在 吗啉 作用下， 以 氯仿 为溶剂， 反应 48.0h， 以12%的产率得到6,7-dichloro-3-methyl-2-[(4-phenylpiperazin-1-yl)carbonyl]quinoxaline 1,4-dioxide
  参考文献：
  名称：

  Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-Oxide derivatives

  摘要：

  As a continuation of our research and with the aim of obtaining new antituberculosis agents which can improve the current chemotherapeutic antituberculosis treatments, new series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis strain H(37)Rv, using the radiometric BACTEC 460-TB methodology. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. The results indicate that some compounds exhibited a good antituberculosis activity and the arylearboxamide analogues 3, 8, and 9 were the most active compounds (EC90/MICI). Also, the cytotoxic effects indicate that these compounds have a good Selectivity Index (SI). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00119-6
• 作为产物：
  描述：

  N-苯基哌嗪 、 乙酰乙酸叔丁酯 以 甲苯 为溶剂， 生成 1-(4-phenylpiperazin-1-yl)butane-1,3-dione
  参考文献：
  名称：

  Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)

  摘要：

  A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I-Kur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.099

文献信息

• Discovery of ((<i>S</i>)-5-(Methoxymethyl)-7-(1-methyl-1<i>H</i>-indol-2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-<i>a</i>]pyrimidin-6-yl)((<i>S</i>)-2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone As a Potent and Selective I_Kur Inhibitor
  作者：Heather J. Finlay、John Lloyd、Wayne Vaccaro、Alexander Kover、Lin Yan、Gauri Bhave、Joseph Prol、Tram Huynh、Rao Bhandaru、Yolanda Caringal、John DiMarco、Jinping Gan、Tim Harper、Christine Huang、Mary Lee Conder、Huabin Sun、Paul Levesque、Michael Blanar、Karnail Atwal、Ruth Wexler

  DOI：10.1021/jm201386u

  日期：2012.4.12

  Subsequent optimization for potency and PK properties lead to the discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol-2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone (13j), with an acceptable PK profile in preclinical species and potent efficacy in the preclinical rabbit atrial effective refractory period (AERP) model.

  先前公开的二氢吡唑并嘧啶是I Kur电流的有效和选择性阻滞剂。这种化学型的潜在缺陷是反应性代谢产物的形成，该代谢产物在体外表现出与蛋白质的共价结合。当在2或3位取代时，该模板产生有效的I Kur抑制剂，对h ERG的选择性不形成反应性代谢产物。随后对效能和PK性质的优化导致发现（（S）-5-（甲氧基甲基）-7-（1-甲基-1 H-吲哚-2-基）-2-（三氟甲基）-4,7-二氢吡唑并[1,5- a ]嘧啶-6-基）（（S）-2-（3-甲基异恶唑-5-基）吡咯烷-1-基）甲酮（13j），在临床前物种中具有可接受的PK曲线，并且在临床前兔心房有效不应期（AERP）模型中具有有效功效。
• HETEROCYCLIC DIHYDROPYRIMIDINES AS POTASSIUM CHANNEL INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1237891B1

  公开（公告）日：2011-09-28
• Heterocyclic dihydropyrimidine compounds
  申请人：Atwal S. Karnail

  公开号：US20070099899A1

  公开（公告）日：2007-05-03

  Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the K v 1 subfamily of voltage gated K + channels, especially inhibitors K v 1.5 which has been linked to the ultra-rapidly activating delayed rectifier K + current I Kur ), methods of using such compounds in the prevention and treatment of arrhythmia and I Kur -associated conditions, and pharmaceutical compositions containing such compounds.
• US7157451B2
  申请人：——

  公开号：US7157451B2

  公开（公告）日：2007-01-02
• US7541362B2
  申请人：——

  公开号：US7541362B2

  公开（公告）日：2009-06-02