6-benzyloxy-2,2-dimethyl-3,4-epoxychroman | 223749-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-benzyloxy-2,2-dimethyl-3,4-epoxychroman
• 英文别名: 2,2-dimethyl-6-phenylmethoxy-1a,7b-dihydrooxireno[2,3-c]chromene
• CAS: 223749-54-0
• 化学式: C₁₈H₁₈O₃
• 分子量: 282.339
• InChiKey: KHZUVBPHLGKYJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-甲基甲磺酰胺 、 6-benzyloxy-2,2-dimethyl-3,4-epoxychroman 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 生成 (+/-)-trans-N-(6-Benzyloxy-3-hydroxy-2,2-dimethylchroman-4-yl)-N-methylmethanesulfonamide
  参考文献：
  名称：

  Synthesis and Activity of Novel and Selective I_Ks-Channel Blockers

  摘要：

  Since the discovery of the I-Ks-potassium channel as the slowly activating component of the delayed rectifier current (I-k) in cardiac tissue, the search for blockers of this current has been intense. During the screening of K-ATP-channel openers of the chromanol type we found that chromanol 293B was able to block I-Ks. Chromanol 293B is a sulfonamide analogue of the K-ATP-channel openers but had no activity on this target. Experiments were initiated to improve the activity and properties based on this lead compound. As a screening model we used Xenopus oocytes injected with human minK (KCNE1). Variations of the aromatic substituent and the sulfonamide group were prepared, and their activity was evaluated. We found that the greatest influence on activity was found in the aromatic substituents. The most active compounds were alkoxy substituted. We chose HMR1556 ((3R, 4S)-(+)-N-[-3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)chroman-4-yl]-N-methyl-ethanesulfonamide) 10a for development as an antiarrhythmic drug. The absolute configuration, resulting from an X-ray single-crystal structure analysis, was determined.

  DOI：

  10.1021/jm0109255
• 作为产物：
  描述：

  氢氧化钾 、 6-benzyloxy-3-bromo-2,2-dimethylchroman-4-ol 以 四氢呋喃 为溶剂， 反应 16.0h， 以giving 8.3 g of 6-benzyloxy-2,2-dimethyl-3,4-epoxychroman, m.p. 70-72° C.的产率得到6-benzyloxy-2,2-dimethyl-3,4-epoxychroman
  参考文献：
  名称：

  Sulfonamide-substituted benzopyran derivatives, processes for their

  摘要：

  磺胺基取代苯并吡喃衍生物，其制备方法，其作为药物的用途，以及包含它们的制药制剂。公式I的化合物##STR1## 其中所述取代基的含义如权利要求中所示，是用于生产预防和治疗心血管疾病，特别是心律失常，治疗胃肠道溃疡或腹泻疾病药物的杰出活性物质。

  公开号：

  US06008245A1

文献信息

• Sulfonamid-substituierte Benzopyranderivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP0913396B1

  公开（公告）日：2003-09-17
• US6008245A
  申请人：——

  公开号：US6008245A

  公开（公告）日：1999-12-28
• [EN] NOVEL BENZOPYRAN COMPOUNDS AND PROCESS FOR THEIR PREPARATION AND USE<br/>[FR] DERIVES DE CHROMANE EN TANT QU'AGONISTES DU RECEPTEUR BETA 3 ADRENERGIQUE
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2003014113A1

  公开（公告）日：2003-02-20

  Novel benzopyran compounds that are useful as beta 3-adrenergic receptor agonists, pharmaceutical compositions containing these compounds, and processes for their preparation and use.
• Sulfonamide-substituted benzopyran derivatives, processes for their
  申请人：Hoechst Marion Roussel Deutschland GmbH

  公开号：US06008245A1

  公开（公告）日：1999-12-28

  Sulfonamide-substituted benzopyran derivatives, processes for their preparation, their use as a medicament, and pharmaceutical preparations comprising them Compounds of the formula I ##STR1## having the meanings of the substituents indicated in the claims are outstandingly active substances for the production of medicaments for the prophylaxis and for the therapy of cardiovascular disorders, in particular arrhythmias, for the treatment of ulcers of the gastrointestinal region or for the treatment of diarrheal diseases.

  磺胺基取代的苯并吡喃衍生物，其制备方法，其作为药物的用途，以及包含它们的药物制剂。具有如下式I的化合物 ##STR1## 其中在索赔中指示的取代基的含义，是用于预防和治疗心血管疾病，特别是心律失常，用于治疗胃肠道溃疡或腹泻疾病的药物的杰出活性物质。
• Synthesis and Activity of Novel and Selective I_Ks-Channel Blockers
  作者：Uwe Gerlach、Joachim Brendel、Hans-Jochen Lang、Erich F. Paulus、Klaus Weidmann、Andrea Brüggemann、Andreas E. Busch、Hartmut Suessbrich、Markus Bleich、Rainer Greger

  DOI：10.1021/jm0109255

  日期：2001.11.1

  Since the discovery of the I-Ks-potassium channel as the slowly activating component of the delayed rectifier current (I-k) in cardiac tissue, the search for blockers of this current has been intense. During the screening of K-ATP-channel openers of the chromanol type we found that chromanol 293B was able to block I-Ks. Chromanol 293B is a sulfonamide analogue of the K-ATP-channel openers but had no activity on this target. Experiments were initiated to improve the activity and properties based on this lead compound. As a screening model we used Xenopus oocytes injected with human minK (KCNE1). Variations of the aromatic substituent and the sulfonamide group were prepared, and their activity was evaluated. We found that the greatest influence on activity was found in the aromatic substituents. The most active compounds were alkoxy substituted. We chose HMR1556 ((3R, 4S)-(+)-N-[-3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)chroman-4-yl]-N-methyl-ethanesulfonamide) 10a for development as an antiarrhythmic drug. The absolute configuration, resulting from an X-ray single-crystal structure analysis, was determined.