4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[4,5]decane | 133882-21-0

• 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: 4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[4,5]decane
• 英文别名: 4-methylidene-3-phenyl-1-oxa-3,8-diazaspiro[4.5]decan-2-one
• CAS: 133882-21-0
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: UJKREDBGQKVDDB-UHFFFAOYSA-N

物化性质

• 沸点：
  369.9±52.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[4,5]decane 在 盐酸 、 甲酸 、 potassium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 生成 8-[2-(4-Fluoro-phenyl)-ethyl]-4-hydroxy-4-methyl-3-phenyl-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：

  8-Formyl-4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[ 4,5]decane 、 一水合肼 、 溶剂黄146 在 氩 、 碳酸氢钠 、 magnesium sulfate 、 crude product 、 乙酸乙酯 、 碳 作用下， 以 乙醇 为溶剂， 以to give the title compound in 41.0% yield, m.p.: 185°-186° C.的产率得到4-methylene-2-oxo-3-phenyl-1-oxa-3,8-diazaspiro[4,5]decane
  参考文献：
  名称：

  2-oxo-1-oxa-8 azaspiro[4,5]decane derivatives, pharmaceutical

  摘要：

  本发明涉及一种新型2-氧代-1-氧杂-8-氮杂螺[4,5]癸烷衍生物，其化学式为(I)：##STR1## 其中，X代表氧或一个>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.1-4烷基，后两个取代基在其芳香基上可以选择一个或多个，相同或不同的卤素，一个或多个C.sub.1-4烷基，C.sub.1-4烷氧基或三卤甲基基团；或对甲苯磺酰基；R.sup.1和R.sup.2一起代表一个亚甲基基团或当X代表>NR基团且R如上定义时，R.sup.1和R.sup.2中的一个可以代表一个羟基，另一个是甲基；R.sup.3代表氢，苄基，(C.sub.1-4烷氧基)羰基，苯氧羰基，苄氧羰基，甲酰基，哌啶-1-基羰基，吗啉-4-基羰基，4-甲基哌嗪-1-基羰基，4-(2-羟乙基)哌嗪-1-基羰基，2-氯-3-烟酰胺基甲酰基或C.sub.1-6烷基甲酰基团，以及它们的酸加合物和季铵盐。

  公开号：

  US05157038A1

文献信息

• 4-methylene-2-oxo-8-azaspiro[4,5]decane derivatives, pharmaceutical
  申请人：Richter Gedeon Vegyeszeti Gyar Rt.

  公开号：US05132303A1

  公开（公告）日：1992-07-21

  The invention relates to novel, therapeutically active 4-methylene-2-oxo-8-azaspiro[4,5]decane derivatives of the compound, ##STR1## wherein X means oxygen or an >NR group, wherein R stands for hydrogen, C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 arylC.sub.1-4 alkyl group, the latter two being optionally substituted on their aromatic moiety by one or more, same or different halogen(s) or one or more C.sub.1-4 alkyl group(s) or by one or more C.sub.1-4 alkoxy group(s); R.sup.3 and R.sup.4, which are the same or different, represent hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trihalomethyl group or hydroxyl group optionally esterified by a C.sub.1-4 alkanoic acid; and is 1 or 2, their isomers, solvates, hydrates, acid addition and quaternary ammonium salts.

  本发明涉及一种新型治疗活性的4-亚甲基-2-氧代-8-氮杂螺[4,5]癸烷衍生物化合物，其化学式为##STR1## 其中X代表氧或>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.1-4烷基，后两者在其芳基上可选择地被一个或多个相同或不同的卤素或一个或多个C.sub.1-4烷基或一个或多个C.sub.1-4烷氧基取代；R.sup.3和R.sup.4，它们相同或不同，代表氢、一个或多个卤素、C.sub.1-4烷基、C.sub.1-4烷氧基、三卤甲基基团或羟基，可选择地被C.sub.1-4烷基酸酯化；且n为1或2，它们的异构体、溶剂化物、水合物、酸加合物和季铵盐。
• 4-Methylene-1-oxa-2-oxo-8-azaspiro[4,5]decane derivatives, pharmaceutical compositions containing them and processes for preparing them
  申请人：RICHTER GEDEON VEGYESZETI GYAR R.T.

  公开号：EP0413516A2

  公开（公告）日：1991-02-20

  This invention relates to 4-methylene-2-oxo-8-azas-piro[4,5]decane derivatives of formula (I), wherein X represents oxygen or NR, wherein R represents hydrogen or alkyl or cycloalkyl, or carbocyclic aryl or carbocyclic aryl-alkyl optionally substituted on the aromatic ring by one or more halogen atoms, alkyl or alkoxy . Ph¹ and Ph², which may be the same or different, each represent phenyl unsubstituted or substituted by one or more halogen atoms or alkyl, alkoxy, trihalomethyl or hydroxy optionally esterified by an alkanoic acid; and n is 1 or 2; and optical isomers and mixtures thereof, and all solvates, hydrates, acid addition and quaternary ammonium salts thereof, to pharmaceutical compositions containing these compounds and processes for their preparation. The compounds of the formula (I) possess antipsychotic properties. Thus, they appear useful for the treatment of psychiatric disorders.

  本发明涉及式 (I) 的 4-亚甲基-2-氧代-8-氮杂螺[4,5]癸烷衍生物、 其中 X 代表氧或 NR，其中 R 代表氢或烷基或环烷基，或碳环芳基或碳环芳烷基，可选择在芳香环上被一个或多个卤素原子、烷基或烷氧基取代。 Ph¹和Ph²可以相同或不同，各自代表未取代的苯基或被一个或多个卤素原子或烷基、烷氧基、三卤甲基或羟基任选酯化的烷酸取代的苯基；以及 n 为 1 或 2； 及其光学异构体和混合物，以及它们的所有溶解物、水合物、酸加成盐和季铵盐，以 及含有这些化合物的药物组合物和它们的制备工艺。 式（I）化合物具有抗精神病特性。因此，它们可用于治疗精神疾病。
• 2-Oxo-1-oxa-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：EP0412820B1

  公开（公告）日：1994-03-02
• 2-Oxo-1-oxa-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：EP0414422B1

  公开（公告）日：1994-04-06
• 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