申请人：Zambon Group S.p.A.
公开号：US05739123A1
公开（公告）日：1998-04-14
Compounds of formula (I), ##STR1## wherein R is a biphenyl group optionally substituted, by one or more substituents, the same or different selected among halogen atoms, hydroxy groups, alkoxy, alkyl thioalkyl or alkoxycarbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety, C.sub.1 -C.sub.3 alkyl groups containing one or more fluorine atoms, carboxy groups, nitro groups, amino or aminocarbonyl groups, acylamino groups, aminosulphonyl groups, momo- or di-alkylamino groups having from 1 to 6 carbon atoms in the alkyl moiety, mono- or di-alkylamino-carbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety; R.sub.1 is a hydrogen atom, a straight or branched C.sub.1 -C.sub.6 alkyl group or an arylalkyl group having from 1 to 6 carbon atoms in the alkyl moiety wherein the aryl is a phenyl, a biphenyl, a napthyl or a 5 or 6 membered aromatic heterocycle with one or two heteroatoms selected among nitrogen, oxygen and sulphur, optionally substituted with one or more substituents, the same or different, selected among halogen atoms, hydroxy groups, alkoxy, alkyl, thioalkyl or alkoxycarbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety, C.sub.1 -C.sub.3 alkyl groups containing one or more fluorine atoms, carboxy groups, nitro groups, amino or aminocarbonyl groups, acylamino groups, aminosulphonyl groups, mono- or di-alkylamino groups having from 1 to 6 carbon atoms in the alkyl moiety, mono- or di-alkylaminocarbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety; R.sub.2 is a straight or branched C.sub.1 -C.sub.6 alkyl group, optionally containing one or more fluorine atoms or one or more --NH-- groups, an arylalkyl, an arylcarbonylaminoalkyl, an arylalkylcarbonylaminoalkyl or an arylaminocarbonylalkyl group having from 1 to 6 carbon atoms and optionally one or more --NH-- groups in the alkyl moiety, the aryl being optionally substituted by one or more substituents, the same or different, selected among halogen atoms, hydroxy groups, alkoxy, alkyl, thioalkyl or alkoxycarbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety, C.sub.1 -C.sub.3 alkyl groups containing one or more fluorine atoms, carboxy groups, nitro groups, amino or aminocarbonyl groups, acylamino groups, aminosulphonyl groups, mono-or di-alkylamino groups having from 1 to 6 carbon atoms in the alkyl moiety, mono- or di-alkylaminocarbonyl groups having from 1 to 6 carbon atoms in the alkyl moiety; m is 0 or 1; X is a hydrogen or fluorine atom; the carbon atom marked with an asterisk is an asymmetric carbon atom; and their pharmaceutically acceptable salts, are described. The compounds of formula (I) are endowed with a mixed ACE-inhibitory and NEP-inhibitory activity and are useful in the treatment of cardiovascular diseases.
公式（I）的化合物，其中R是一个二苯基团，可选择地被一个或多个取代基取代，这些取代基可以是相同的或不同的，包括卤素原子、羟基、烷氧基、烷
硫基或烷氧羰基基团，在烷基部分含有1到6个碳原子，含有一个或多个
氟原子的C.sub.1 -C.sub.3烷基基团，羧基、硝基、
氨基或
氨基羰基基团、酰
氨基基团、
氨基磺酰基团、含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基基团，含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基羰基基团；R.sub.1是氢原子、直链或支链的C.sub.1 -C.sub.6烷基基团或含有1到6个碳原子的芳基烷基基团，其中芳基是苯基、二苯基、
萘基或含有氮、氧和
硫等一到两个杂原子的5或6元芳杂环，可选择地被一个或多个取代基取代，这些取代基可以是相同的或不同的，包括卤素原子、羟基、烷氧基、烷基、
硫基或烷氧羰基基团，在烷基部分含有1到6个碳原子，含有一个或多个
氟原子的C.sub.1 -C.sub.3烷基基团，羧基、硝基、
氨基或
氨基羰基基团、酰
氨基基团、
氨基磺酰基团、含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基基团，含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基羰基基团；R.sub.2是直链或支链的C.sub.1 -C.sub.6烷基基团，可选择地含有一个或多个
氟原子或一个或多个--NH--基团，芳基烷基、芳基羰基
氨基烷基、芳基烷基羰基
氨基烷基或芳基
氨基羰基烷基基团，含有1到6个碳原子并可选择地含有一个或多个--NH--基团，在烷基部分，芳基可选择地被一个或多个取代基取代，这些取代基可以是相同的或不同的，包括卤素原子、羟基、烷氧基、烷基、
硫基或烷氧羰基基团，在烷基部分含有1到6个碳原子，含有一个或多个
氟原子的C.sub.1 -C.sub.3烷基基团，羧基、硝基、
氨基或
氨基羰基基团、酰
氨基基团、
氨基磺酰基团、含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基基团，含有1到6个碳原子的烷基部分的单烷基或双烷基
氨基羰基基团；m为0或1；X为氢或
氟原子；星号标记的碳原子是一个不对称碳原子；以及它们的药用盐。公式（I）的化合物具有混合的ACE抑制和
NEP抑制活性，并可用于治疗心血管疾病。
