8-(4-氟苯基)-1,4-二氧杂螺[4.5]癸烷-8-羧酸 | 56327-03-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 8-(4-氟苯基)-1,4-二氧杂螺[4.5]癸烷-8-羧酸
• 英文名称: 8-(4-fluoro-phenyl)-1,4-dioxa-spiro[4.5]decane-8-carboxylic acid
• 英文别名: 4-carboxy-4-(p-fluorophenyl)cyclohexanone, ethylene ketal；4-carboxy-4-(4-fluorophenyl)cyclohexanone, ethylene ketal；1,4-Dioxaspiro[4.5]decane-8-carboxylic acid, 8-(4-fluorophenyl)-；8-(4-fluorophenyl)-1,4-dioxaspiro[4.5]decane-8-carboxylic acid
• CAS: 56327-03-8
• 化学式: C₁₅H₁₇FO₄
• 分子量: 280.296
• InChiKey: KCPDEASEGSDFNA-UHFFFAOYSA-N

物化性质

• 熔点：
  117-122 °C
• 沸点：
  434.2±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(4-氟苯基)-1,4-二氧杂螺[4.5]癸烷-8-羧酸 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 4-(p-fluorophenyl)-4-dimethylaminocyclohexan-1-one, ethylene ketal
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014
• 作为产物：
  描述：

  8-(4-氟-苯基)-1,4-二噁螺[4.5]癸烷-8-甲腈 在 乙二醇 、 potassium hydroxide 作用下， 生成 8-(4-氟苯基)-1,4-二氧杂螺[4.5]癸烷-8-羧酸
  参考文献：
  名称：

  Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors

  摘要：

  The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11 beta-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.129

文献信息

• 1-(4-Aryl-cyclohexyl)piperidine derivatives, method of use thereof and
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US04329353A1

  公开（公告）日：1982-05-11

  Novel 1-[1-(4-aryl-cyclohexyl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-ones and 1-aryl-8-(4-aryl-cyclohexyl)-1,3,8-triazaspiro[4,5]decan-4-ones which are useful as antiemetic-and neuroleptic agents.

  新颖的化合物1-[1-(4-芳基-环己基)-4-哌啶基]-1,3-二氢-2H-苯并咪唑-2-酮和1-芳基-8-(4-芳基-环己基)-1,3,8-三氮杂螺[4,5]癸烷-4-酮，可用作抗恶心和抗精神病药物。
• Butyrophenones as hypotensive agents. Derivatives of 4-aryl-4-(hydroxymethyl)cyclohexylamine
  作者：Daniel Lednicer、D. Edward Emmert、Alan D. Rudzik、Boyd E. Graham

  DOI：10.1021/jm00240a014

  日期：1975.6

  preparation of butyrophenone derivatives of 4-aryl-4-(hydroxymethyl)cyclohex-1-ylamines starting from the corresponding 4-cyano-4-phenylcyclohexan-1-ones is described. Substitution was varied with both rings; both isomers of 4-phenyl-4-(hydroxymethyl)cyclohex-1-ylamine were characterized. Those derivatives which carried p-fluoro substitution on the butyrophenone exhibited hypotensive activity in the rat with

  描述了从相应的4-氰基-4-苯基环己酮-1-酮开始制备4-芳基-4-（羟甲基）环己-1-基胺的丁苯酮衍生物。两个环都有不同的取代基；对4-苯基-4-（羟甲基）环己-1-基胺的两种异构体进行了表征。与缺乏羟甲基的化合物相比，在丁苯酮上进行对氟取代的那些衍生物在大鼠中表现出降压活性，而CNS活性降低。讨论了取代对4-芳基环的影响。
• Cycloalkylamine substituted isoquinoline and isoquinolinone derivatives
  申请人：PLETTENBURG Oliver

  公开号：US20100056553A1

  公开（公告）日：2010-03-04

  The invention relates to 6-substituted isoquinoline and isoquinolinone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

  本发明涉及公式（I）的6-取代的异喹啉和异喹啉酮衍生物，可用于治疗和/或预防与Rho-激酶和/或Rho-激酶介导的肌球蛋白轻链磷酸酶的磷酸化相关的疾病，以及含有这些化合物的组合物。
• WO2008/77556
  申请人：——

  公开号：——

  公开（公告）日：——
• LEDNICER D.; VOIGTLANDER P. F.; EMMERT D. E., J. MED. CHEM., 1980, 23, NO 4, 424-430
  作者：LEDNICER D.、 VOIGTLANDER P. F.、 EMMERT D. E.

  DOI：——

  日期：——