1-oxa-2-oxo-4-methylene-3-phenyl-8-(2-phenylethyl)-3,8-diazaspiro[ 4,5]decane | 134069-60-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 1-oxa-2-oxo-4-methylene-3-phenyl-8-(2-phenylethyl)-3,8-diazaspiro[ 4,5]decane
• 英文别名: 1-Oxa-3,8-diazaspiro(4.5)decan-2-one, 4-methylene-3-phenyl-8-(2-phenylethyl)-；4-methylidene-3-phenyl-8-(2-phenylethyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one
• CAS: 134069-60-6
• 化学式: C₂₂H₂₄N₂O₂
• 分子量: 348.445
• InChiKey: AEYHMYIOVQXIRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[4,5]decane 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 以72%的产率得到1-oxa-2-oxo-4-methylene-3-phenyl-8-(2-phenylethyl)-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-2-oxo-8-azaspiro(4,5)decane derivatives, pharmaceutical
  申请人：Richter Gedeon Vegyeszeti Gyar Rt.

  公开号：US05118687A1

  公开（公告）日：1992-06-02

  The invention relates to novel compounds 1-oxa-2-oxo-8- of the formula (I), ##STR1## wherein X means oxygen or an >NR group, wherein R stands for hydrogen, a C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.10-4 alkyl group, the latter two groups are optionally substituted on their aromatic moiety by one or more, same or different halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy group(s); R.sup.1 and R.sup.2 together represent a methylene group or, when X stands for an >NR group, wherein R is as defined above, one of R.sup.1 and R.sup.2 may represent a hydroxyl group whereas the other is a methyl group; R.sup.3 stands for hydrogen or a phenyl group optionally substituted by one or more halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy or hydroxyl group(s); R.sup.4 means hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxyl or trihalomethyl group(s); and n is 1, 2 or 3 as well as their acid addition and quaternary ammonium salts.

  本发明涉及一种新型化合物1-氧杂-2-酮-8-的式子(I)，其中X表示氧或>NR基团，其中R代表氢，C.sub.1-12烷基，C.sub.3-6环烷基，碳环C.sub.6-10芳基或碳环C.sub.6-10芳基-C.sub.10-4烷基，后两个基团在它们的芳香基上可以选择性地被一个或多个相同或不同的卤素，一个或多个C.sub.1-4烷基或C.sub.1-4烷氧基取代；R.sup.1和R.sup.2一起表示亚甲基基团，或者当X表示>NR基团，其中R如上所定义时，R.sup.1和R.sup.2中的一个可以表示羟基，而另一个是甲基基团；R.sup.3表示氢或一种芳基，可以选择性地被一个或多个卤素，一个或多个C.sub.1-4烷基或C.sub.1-4烷氧基或羟基取代；R.sup.4表示氢，一个或多个卤素，C.sub.1-4烷基，C.sub.1-4烷氧基，羟基或三卤甲基基团；n为1、2或3，以及它们的酸加成物和季铵盐。
• 1-Oxa-2-oxo-8-azaspiro[4,5] decane derivatives, processes for their preparation and pharmaceutical compositions thereof
  申请人：RICHTER GEDEON VEGYESZETI GYAR R.T.

  公开号：EP0414421B1

  公开（公告）日：1994-04-06
• 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.