1-Oxa-2-oxo-3-isopropyl-4-methylene-8-[4,4-bis(4-fluorophenyl)butyl]-3,8-diazaspiro[4,5]decane | 134097-79-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-Oxa-2-oxo-3-isopropyl-4-methylene-8-[4,4-bis(4-fluorophenyl)butyl]-3,8-diazaspiro[4,5]decane
• 英文别名: 8-[4,4-Bis(4-fluorophenyl)butyl]-4-methylidene-3-propan-2-yl-1-oxa-3,8-diazaspiro[4.5]decan-2-one
• CAS: 134097-79-3
• 化学式: C₂₇H₃₂F₂N₂O₂
• 分子量: 454.56
• InChiKey: CPMKHORGMCWPGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-Oxa-2-oxo-3-isopropyl-4-methylene-8-[4,4-bis(4-fluorophenyl)butyl]-3,8-diazaspiro[4,5]decane 在 盐酸 、 甲酸 作用下， 以96%的产率得到8-[4,4-Bis-(4-fluoro-phenyl)-butyl]-4-hydroxy-3-isopropyl-4-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one; hydrochloride
  参考文献：
  名称：

  1-Oxa-3,8-diazaspiro[4.5]decan-2-one derivatives with a potent inhibitory effect on neural Ca-uptake and protecting action against TET-induced brain edema and memory and learning deficits

  摘要：

  A series of novel 1-oxa-3,8-diazaspiro[4.5]decan-2-one derivatives 8-71 were synthesized. Several representatives were examined for their in vitro inhibitory action on Ca-45-uptake into cerebrocortical synaptosomes depolarized by potassium and veratrine and on triethyltin-induced brain edema. Of the compounds displaying most potent inhibitory action on veratrine-induced Ca-45-uptake into cerebrocortical synaptosomes and outstanding protection against triethyltin chloride (TET) induced brain edema in rats, four were tested for their antihypoxic action and prevention of learning and memory deficits elicited by various agents leg, electroshock, diazepam, scopolamine, carbon dioxide and normobaric hypoxia). In some of these tests the four compounds showed remarkable protecting/restoring activity. It is assumed that the beneficial effects of these compounds in brain edema formation are probably related to their actions on intracellular Ca2+- and Na+-movements. These cellular effects may also play role in their antiamnesic actions, but other mechanisms may also be involved. On the basis of results obtained in the tests used, the pharmacological profile of the novel 1-oxa-3,8-diazaspiro [4.5]decan-2-one derivatives seems to differ from that of known Ca2+-antagonists such as flunarizine or nimodipine and Na+-channel blocker, phenytoin. Out of the four most active compounds tested, one (44) was selected for further investigation and this compound is currently under preclinical development with the code name of RGH-2716 or TDN-345.

  DOI：

  10.1016/s0223-5234(97)84359-0
• 作为产物：
  描述：

  4,4,-二(4-氟苯)氯丁烷 、 3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]-decane 在 potassium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 以74%的产率得到1-Oxa-2-oxo-3-isopropyl-4-methylene-8-[4,4-bis(4-fluorophenyl)butyl]-3,8-diazaspiro[4,5]decane
  参考文献：
  名称：

  1-Oxa-3,8-diazaspiro[4.5]decan-2-one derivatives with a potent inhibitory effect on neural Ca-uptake and protecting action against TET-induced brain edema and memory and learning deficits

  摘要：

  A series of novel 1-oxa-3,8-diazaspiro[4.5]decan-2-one derivatives 8-71 were synthesized. Several representatives were examined for their in vitro inhibitory action on Ca-45-uptake into cerebrocortical synaptosomes depolarized by potassium and veratrine and on triethyltin-induced brain edema. Of the compounds displaying most potent inhibitory action on veratrine-induced Ca-45-uptake into cerebrocortical synaptosomes and outstanding protection against triethyltin chloride (TET) induced brain edema in rats, four were tested for their antihypoxic action and prevention of learning and memory deficits elicited by various agents leg, electroshock, diazepam, scopolamine, carbon dioxide and normobaric hypoxia). In some of these tests the four compounds showed remarkable protecting/restoring activity. It is assumed that the beneficial effects of these compounds in brain edema formation are probably related to their actions on intracellular Ca2+- and Na+-movements. These cellular effects may also play role in their antiamnesic actions, but other mechanisms may also be involved. On the basis of results obtained in the tests used, the pharmacological profile of the novel 1-oxa-3,8-diazaspiro [4.5]decan-2-one derivatives seems to differ from that of known Ca2+-antagonists such as flunarizine or nimodipine and Na+-channel blocker, phenytoin. Out of the four most active compounds tested, one (44) was selected for further investigation and this compound is currently under preclinical development with the code name of RGH-2716 or TDN-345.

  DOI：

  10.1016/s0223-5234(97)84359-0

文献信息

• 1-Oxa-3,8-diazaspiro[4.5]decan-2-one derivatives with a potent inhibitory effect on neural Ca-uptake and protecting action against TET-induced brain edema and memory and learning deficits
  作者：E Tóth、B Kiss、A Gere、E Kárpáti、J Törley、É Pálosi、Á Kis-Varga、M Paróczai、S Szabó、D Groó、I Laszlovszky、E Lapis、K Csomor、L Szporny

  DOI：10.1016/s0223-5234(97)84359-0

  日期：1997.1

  A series of novel 1-oxa-3,8-diazaspiro[4.5]decan-2-one derivatives 8-71 were synthesized. Several representatives were examined for their in vitro inhibitory action on Ca-45-uptake into cerebrocortical synaptosomes depolarized by potassium and veratrine and on triethyltin-induced brain edema. Of the compounds displaying most potent inhibitory action on veratrine-induced Ca-45-uptake into cerebrocortical synaptosomes and outstanding protection against triethyltin chloride (TET) induced brain edema in rats, four were tested for their antihypoxic action and prevention of learning and memory deficits elicited by various agents leg, electroshock, diazepam, scopolamine, carbon dioxide and normobaric hypoxia). In some of these tests the four compounds showed remarkable protecting/restoring activity. It is assumed that the beneficial effects of these compounds in brain edema formation are probably related to their actions on intracellular Ca2+- and Na+-movements. These cellular effects may also play role in their antiamnesic actions, but other mechanisms may also be involved. On the basis of results obtained in the tests used, the pharmacological profile of the novel 1-oxa-3,8-diazaspiro [4.5]decan-2-one derivatives seems to differ from that of known Ca2+-antagonists such as flunarizine or nimodipine and Na+-channel blocker, phenytoin. Out of the four most active compounds tested, one (44) was selected for further investigation and this compound is currently under preclinical development with the code name of RGH-2716 or TDN-345.