1,4-二溴丁烷-2-酮 | 52011-50-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1,4-二溴丁烷-2-酮
• 英文名称: 1,4-dibromobutan-2-one
• 英文别名: 1,4-dibromo-butan-2-one；1,4-Dibrom-butan-2-on；1,4-dibromobutanone；1,3-Dibrom-butanon-(2)；1,4-Dibrombutan-2-on
• CAS: 52011-50-4
• 化学式: C₄H₆Br₂O
• 分子量: 229.899
• InChiKey: OHXYQDOETYHEDS-UHFFFAOYSA-N

物化性质

• 沸点：
  77 °C(Press: 0.1 Torr)
• 密度：
  1.947±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  7
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-((2-(三甲基甲硅烷基)乙氧基)甲基)-1H-吡咯并[2,3-b]吡啶-2(3H)-酮 、 1,4-二溴丁烷-2-酮 在 1,4-二溴丁烷-2-酮 作用下， 生成 (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione
  参考文献：
  名称：

  哌啶酮羧酰胺氮杂茚满CGRP受体拮抗剂

  摘要：

  本发明涉及式I的哌啶酮羧酰胺氮杂茚满衍生物，其是CGRP受体的拮抗剂，并可用于治疗或预防其中涉及CGRP的疾病，诸如偏头痛。本发明还涉及含有这些化合物的药物组合物和这些化合物与组合物在预防或治疗其中涉及CGRP的这样的疾病中的用途。

  公开号：

  CN103328478A
• 作为产物：
  描述：

  4-溴丁烷-2-酮 在 溴 作用下， 以 甲醇 为溶剂， 生成 1,4-二溴丁烷-2-酮
  参考文献：
  名称：

  Probing the active site of rat porphobilinogen synthase using newly developed inhibitors

  摘要：

  The structurally related tetrapyrrolic pigments are a group of natural products that participate in many of the fundamental biosynthetic and catabolic processes of living organisms. Porphobilinogen synthase catalyzes a rate-limiting step for the biosyntheses of tetrapyrrolic natural products. In the present study, a variety of new substrate analogs and reaction intermediate analogs were synthesized, which were used as probes for studying the active site of rat porphobilinogen synthase. The compounds 1, 3, 6, 9, 14, 16, and 28 were found to be competitive inhibitors of rat porphobilinogen synthase with inhibition constants ranging from 0.96 to 73.04 mM. Compounds 7, 10, 12, 13, 15, 17, 18, and 26 were found to be irreversible enzyme inhibitors. For irreversible inhibitors, loose-binding inhibitors were found to give stronger inactivation. The amino group and carboxyl group of the analogs were found to be important for their binding to the enzyme. This study increased our understanding of the active site of porphobilinogen synthase. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2008.11.001
• 作为试剂：
  描述：

  1-((2-(三甲基甲硅烷基)乙氧基)甲基)-1H-吡咯并[2,3-b]吡啶-2(3H)-酮 、 1,4-二溴丁烷-2-酮 在 1,4-二溴丁烷-2-酮 作用下， 生成 (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione
  参考文献：
  名称：

  Substituted monocyclic CGRP receptor antagonists

  摘要：

  公式I的化合物：（其中变量A1，A2，A3，A4，m，n，J，Q，R4，Ea，Eb，Ec，R6，R7，Re，Rf，RPG和Y如本文所述），它们是CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物和组合物在预防或治疗涉及CGRP的疾病方面的用途。

  公开号：

  US20070265225A1

文献信息

• [EN] IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZOLINONE EN TANT QU'ANTAGONISTES DE RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010077752A1

  公开（公告）日：2010-07-08

  The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及嘧啶啉酮衍生物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions − A Direct Route to Spirocyclopropane-Annulated Azepinone Derivatives
  作者：Armin de Meijere、Malte von Seebach、Sergei I. Kozhushkov、Roland Boese、Dieter Bläser、Stefano Cicchi、Tula Dimoulas、Alberto Brandi

  DOI：10.1002/1099-0690(200110)2001:20<3789::aid-ejoc3789>3.0.co;2-o

  日期：2001.10

  Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15−17, with the spirobutane

  从环丁烷羧酸乙酯 (4) (39% 总产率) 开始，通过新的三步顺序制备了数克数量的环亚丁基环丙烷 (7)。苯基- (9)、吡啶基- (10) 和新制备的（四步，总产率 43%）螺环硝酮 11-7 的 1,3-偶极环加成导致相应加合物 15-17 的区域选择性形成，螺丁烷部分与恶唑烷环中的氧原子相邻，产率分别为 52%、84% 和 48%。在快速真空热解条件下，环加合物 15-17 经历热重排，四元环打开，分别以 32%、30% 和 19% 的产率提供螺环丙烷化氮杂酮 21-23。在 17 的情况下，也分离出吲哚里西酮 25（产率 13%）。
• [EN] HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP HÉTÉROCYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169565A1

  公开（公告）日：2013-11-14

  The present invention is directed to heterocyclic compounds which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及杂环化合物，其为CGRP受体拮抗剂，并可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的疾病中使用这些化合物和组合物。
• [EN] MONOCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS CGRP MONOCYCLIQUES
  申请人：MERCK & CO INC

  公开号：WO2009120652A3

  公开（公告）日：2009-12-30
• Ubrogepant. Calcitonin gene-related peptide (CGRP) receptor antagonist, Treatment of migraine
  作者：J. Gras

  DOI：10.1358/dof.2019.44.11.3035581

  日期：——

  Migraineis ranked as the sixth cause of years lost due to disability, with around 1.04 billion migraine sufferers globally. Triptans are considered the standard for acute migraine treatment, but an important number of migraineurs do not respond to them and these drugs are contraindicated in patients with cardiovascular disease. Migraine therapy is currently undergoing tremendous development, i.e., 5-HT1F receptor agonists (ditans), anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies, and small-molecule CGRP receptor antagonists (gepants). Ubrogepant (MK-1620) is a small-molecule, potent and selective CGRP receptor antagonist. In two phase III clinical trials (ACHIEVE I and II), ubrogepant showed, at 2 hours, significant percentages of pain freedom, and absence of the most bothersome symptoms in migraine patients. In a phase III study to assess the long-term (52-week) safety and tolerability, ubrogepant displayed good tolerability, and no signs of hepatic toxicity. In March 2019, the U.S. Food and Drug Administration accepted the new drug application (NDA) for ubrogepant for the acute treatment of migraine.