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:EP0414421A2
公开(公告)日:1991-02-27
The invention relates to 1-oxa-2-oxo-8-azasprio [4,5]decane derivatives of formula (I),
wherein
X represents an oxygen atom or an NR group,
wherein
R represents a hydrogen atom or a C₁₋₁₂ alkyl or C₃₋₆ cycloalkyl group, or a carbocyclic C₆₋₁₀ aryl or carbocyclic C₆₋₁₀ aryl-C₁₋₁₄ alkyl group optionally substituted on the aromatic ring by one or more halogen atoms, C₁₋₄ alkyl or C₁₋₄ alkoxy groups;
R¹ and R² together represent a methylene group or, when X is a NR group, one of R¹ and R² additionally represents a hydroxyl group and the other additionally represents a methyl group;
R³ represents a hydrogen atom or a phenyl group optionally substituted by one or more halogen atoms, C₁₋₄ alkyl, C₁₋₄ alkoxy or hydroxyl group;
Ph represents a phenyl group unsubstituted or substituted by one or more halogen atoms, C₁₋₄ alkyl, C₁₋₄ alkoxy, hydroxyl or trihalomethyl groups; and
n is 1, 2, 3;
and optical isomers and mixtures thereof and all acid addition and quaternary ammonium salts thereof.
The invention further relates to pharmaceutical compositions containing these compounds and processes for their preparation.
The compounds of formula (I) possess calcium, uptake-inhibiting, antihypoxic and antianoxic properties and a low toxicity. Thus, they are useful for the treatment of brain damage of various origin.
本发明涉及式 (I) 的 1-oxa-2-oxo-8-azasprio [4,5]decane 衍生物、
其中
X 代表氧原子或 NR 基团、
其中
R 代表氢原子或 C₁₋₁₂ 烷基或 C₃₋₆ 环烷基、或碳环 C₆₋₁₀ 芳基或碳环 C₆₋₁₀ 芳基-C₁₋₁₄烷基,可选择在芳香环上被一个或多个卤素原子、C₁₋₄烷基或 C₁₋₄烷氧基取代;
R¹和R²共同代表亚甲基,或者当X为NR基团时,R¹和R²中的一个另外代表羟基,另一个另外代表甲基;
R³ 代表氢原子或任选被一个或多个卤素原子、C₁₋₄ 烷基、C₁₋₄ 烷氧基或羟基取代的苯基;
Ph 代表未被取代或被一个或多个卤素原子、C₁₋₄ 烷基、C₁₋₄ 烷氧基、羟基或三卤甲基取代的苯基;以及
n 为 1、2、3;
及其光学异构体和混合物,以及所有酸加成盐和季铵盐。
本发明还涉及含有这些化合物的药物组合物及其制备工艺。
式(I)化合物具有钙、吸收抑制、抗缺氧和抗缺氧特性,且毒性低。因此,它们可用于治疗各种原因引起的脑损伤。