(4-methoxymethoxy-cyclohexyl)-methanol | 1067230-30-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-methoxymethoxy-cyclohexyl)-methanol
• 英文别名: [4-(Methoxymethoxy)cyclohexyl]methanol
• CAS: 1067230-30-1
• 化学式: C₉H₁₈O₃
• 分子量: 174.24
• InChiKey: ZVNCJOXXJNMCSK-UHFFFAOYSA-N

物化性质

• 沸点：
  243.4±10.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-methoxymethoxy-cyclohexyl)-methanol 在 草酰氯 、 碘 、 magnesium 、 二甲基亚砜 、 pyridinium chlorochromate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 cyclohexyl(4-(methoxymethoxy)cyclohexyl)methanone
  参考文献：
  名称：

  Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

  摘要：

  We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.

  DOI：

  10.1021/acs.jmedchem.6b01592
• 作为产物：
  描述：

  4-(Methoxymethoxy)cyclohexane-1-carboxylic acid 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.5h， 生成 (4-methoxymethoxy-cyclohexyl)-methanol
  参考文献：
  名称：

  Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

  摘要：

  We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.

  DOI：

  10.1021/acs.jmedchem.6b01592

文献信息

• Heterocylic antiviral compounds
  申请人：Rotstein David Mark

  公开号：US20080249087A1

  公开（公告）日：2008-10-09

  This invention relates to piperidine derivatives of formula I wherein R 1 , R 2 , R 3 and R 4 are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), rheumatoid arthritis, solid organ transplant reject (graft vs. host disease), asthma and COPD.

  这项发明涉及式I的哌啶衍生物，其中R1、R2、R3和R4如本文所定义，在治疗各种疾病中有用，包括那些涉及CCR5受体调节的疾病。目前这些衍生物可以治疗或预防的疾病包括HIV和遗传相关的逆转录病毒感染（以及由此导致的获得性免疫缺陷综合症，艾滋病），类风湿性关节炎，固体器官移植排斥（移植物抗宿主病），哮喘和慢性阻塞性肺病（COPD）。
• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2142555A1

  公开（公告）日：2010-01-13
• US7625891B2
  申请人：——

  公开号：US7625891B2

  公开（公告）日：2009-12-01
• [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ANTIVIRAUX
  申请人：HOFFMANN LA ROCHE

  公开号：WO2008119663A1

  公开（公告）日：2008-10-09

  [EN] This invention relates to piperidine derivatives of formula (I) wherein R¹, R², R³ and R⁴ are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), rheumatoid arthritis, solid organ transplant reject (graft vs. host disease), asthma and COPD.
  [FR] Cette invention porte sur des dérivés de pipéridine de formule (I) dans laquelle R¹, R², R³ et R⁴ sont tels que définis présentement, utiles dans le traitement d'une diversité de troubles, comprenant ceux dans lesquels la modulation de récepteurs de CCR5 est impliquée. Les troubles qui peuvent être traités ou prévenus par les présents dérivés comprennent les infections par le VIH et les rétrovirus génétiquement apparentés (et le syndrome d'immunodéficience acquise résultant, SIDA), l'arthrite rhumatoïde, le rejet de greffe d'organe solide (réaction du greffon contre l'hôte), l'asthme et la bronchopneumopathie chronique obstructive (COPD).