2,2-dimethyl-2H-chromene-8-carbaldehyde | 355837-29-5

• 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: 2,2-dimethyl-2H-chromene-8-carbaldehyde
• 英文别名: 2,2-dimethylchromene-8-carbaldehyde
• CAS: 355837-29-5
• 化学式: C₁₂H₁₂O₂
• 分子量: 188.226
• InChiKey: HNUCJTPKNSBSHO-UHFFFAOYSA-N

物化性质

• 沸点：
  305.0±42.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-2H-chromene-8-carbaldehyde 在 palladium 10% on activated carbon 、 2,2,6,6-四甲基哌啶氧化物 氢气 、 sodium hypochlorite 、 碳酸氢钠 、 sodium bromide 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 2.0h， 以88%的产率得到2,2-dimethylchromane-8-carbaldehyde
  参考文献：
  名称：

  WO2007/30061

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(1',1'-dimethylpropargyloxy)benzaldehyde 在 盐酸 、 水 、 Sodium sulfate-III 、 crude product 作用下， 以 N,N-二乙基苯胺 、 正庚烷 为溶剂， 反应 1.0h， 以to afford the title compound as an orange oil (0.54 g, 49%)的产率得到2,2-dimethyl-2H-chromene-8-carbaldehyde
  参考文献：
  名称：

  NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES

  摘要：

  本发明提供了一般式为的化合物，其中A、B、p、w、x、y和z的定义如规范中所述，以及其制备方法、包含它们的药物组合物和它们在治疗中的应用。

  公开号：

  US20090156575A1

文献信息

• Examining the structure-activity relationship of benzopyran-based inhibitors of the hypoxia inducible factor-1 pathway
  作者：Jalisa Ferguson、Zeus De Los Santos、Narra Devi、Erwin Van Meir、Sarah Zingales、Binghe Wang

  DOI：10.1016/j.bmcl.2017.02.073

  日期：2017.4

  Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or nonexistent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1 alpha complex formation. A library of sulfonamide analogs has been designed and synthesized with the intent of examining the SAR of this series of compounds and improving potency and physicochemical properties as compared with lead compounds 1 and 2. At the end, we have achieved a thorough understanding of the structural features critical for future optimization work. (C) 2017 Elsevier Ltd. All rights reserved.
• Increasing Selectivity of CC Chemokine Receptor 8 Antagonists by Engineering Nondesolvation Related Interactions with the Intended and Off-Target Binding Sites
  作者：Igor Shamovsky、Chris de Graaf、Lisa Alderin、Malena Bengtsson、Håkan Bladh、Lena Börjesson、Stephen Connolly、Hazel J. Dyke、Marco van den Heuvel、Henrik Johansson、Bo-Göran Josefsson、Anna Kristoffersson、Tero Linnanen、Annea Lisius、Roope Männikkö、Bo Nordén、Steve Price、Lena Ripa、Didier Rognan、Alexander Rosendahl、Marco Skrinjar、Klaus Urbahns

  DOI：10.1021/jm900713y

  日期：2009.12.10

  The metabolic stability and selectivity of a series of CCR8 antagonists against binding to the hERG ion channel and cytochrome Cyp2D6 are studied by principal component analysis. It is demonstrated that an efficient way of increasing metabolic stability and selectivity of this series is to decrease compound lipophilicity by engineering nondesolvation related attractive interactions with CCR8, as rationalized by three-dimensional receptor models. Although Such polar interactions led to increased compound selectivity, such a strategy could also jeopardize the DMPK profile of compounds. However, once increased potency is found, the lipophilicity can be readjusted by engineering hydrophobic substituents that fit to CCR8 but do not fit to hERG. Several such lipophilic fragments are identified by two-dimensional fragment-based QSAR analysis. Electrophysiological measurements and site-directed mutagenesis studies indicated that the repulsive interactions of these fragments with hERG are caused by steric hindrances with residue F656.
• Continuous Processing to Control a Potentially Hazardous Process:  Conversion of Aryl 1,1-Dimethylpropargyl Ethers to 2,2-Dimethylchromenes (2,2-Dimethyl-2<i>H</i>-1-Benzopyrans)
  作者：Ricardo J. Bogaert-Alvarez、Paul Demena、Gus Kodersha、Robert E. Polomski、N. Soundararajan、Steve S. Y. Wang

  DOI：10.1021/op0100504

  日期：2001.11.1

  The thermal Claisen rearrangement of 4-cyanophenyl 1,1-dimethylpropargyl ether (4) to 6-cyano-2,2-dimethylchromene (5), (6-eyano-2,2-dimethyl-2H-1-benzopyran), which is used in the synthesis of a potassium channel activator drug candidate, BMS-180448, created a significant process development issue. The resulting large heat release in this conversion posed not only a safety risk but could also cause product degradation if done in a batch-wise manner. The solution was to exploit the high surface-to-volume ratio of a plug-flow reactor that would maximize the heat transfer, thereby permitting tight and responsive temperature with better reaction control. In the course of successfully testing the plug-flow concept on "micro"-flow scale (gram quantity) and "kilo"-flow scale (similar to 10 kg), a generalized mathematical model capable of predicting the reaction performance based on the physical properties of any given plug-flow reactor was generated. The model provides requisite information to design and operate a plug-flow reactor of any size for this reaction. This model would optimize reaction conditions for an acquired reactor system capable of producing similar to7 kg/h of the dimethylchromene. Application of plug-flow reactor technology enabled production of high quality 2,2-dimethylchromenes in good yield (> 98 mol %) without the use of solvents and with virtually no waste streams.
• [EN] NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES<br/>[FR] NOUVEAUX DIAZASPIROALCANES ET LEUR UTILISATION POUR LE TRAITEMENT DE MALADIES MEDIEES PAR CCR8
  申请人：ASTRAZENECA AB

  公开号：WO2007030061A1

  公开（公告）日：2007-03-15

  [EN] The invention provides compounds of general formula (I) wherein A, B, p, w, x, y, and z are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
  [FR] L'invention concerne des composés représentés par la formule générale (I) dans laquelle A, B, p, w, x, y et z sont tels que définis dans le descriptif, des procédés de préparation desdits composés, des compositions pharmaceutiques contenant lesdits composés et leur utilisation à des fins thérapeutiques.