申请人:Shosuke Okamoto
公开号:US04895842A1
公开(公告)日:1990-01-23
A phenylalanine derivative having the formula (I): ##STR1## where R.sup.1 and R.sup.2 are independently hydrogen provided that both R.sup.1 and R.sup.2 are not hydrogen at the same time; C.sub.1 -C.sub.8 alkyl which may be substituted with hydroxy, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylmercapto, C.sub.1 -C.sub.4 alkoxy, carbamoyl, sulfamoyl, pyridyl, or phenyl which may further be substituted with nitro, C.sub.1 -C.sub.4 alkoxy, or halogen; C.sub.6 -C.sub.8 cycloalkyl which may be substituted with hydroxy, C.sub.1 -C.sub.4 alkoxy, hydroxylcarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, or C.sub.1 -C.sub.4 alkyl; phenyl which may be substituted with halogen, nitro, trifluoromethyl, C.sub.1 -C.sub.4 alkoxy C.sub.1 C.sub.4 alkylmercapto, C.sub.1 -C.sub.4 alkylcarbonyl, phenylcarbonyl, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, carbamoyl, sulfamoyl, amidino, pyridylcarbonyl, or C.sub.1 -C.sub.6 alkyl which may further be substituted with C.sub.1 -C.sub.4 alkylcarbonyl, hydroxycarbonyl, or C.sub.1 -C.sub.4 alkoxycarbonyl; pyridyl which may be substituted with halogen or C.sub.1 -C.sub.4 alkoxy; pyrimidyl; N-benzylazacyclohexyl; and R.sup.1 and R.sup.2 may form with the nitrogen atom attached thereto a ring structure as morpholino; thiomorpholino; piperazino which may be substituted with phenylcarbonyl, benzyl, or C.sub.1 -C.sub.4 alkyl; pyrrolidyl which may be substituted with hydroxycarbonyl or C.sub.1 -C.sub.4 alkoxycarbonyl; and piperidino substituted with C.sub.1 -C.sub.4 alkyl, phenyl C.sub.1 -C.sub.4 alkyl, phenycarbonyl, or C.sub.1 -C.sub.4 alkoxycarbonyl; X is hydrogen; nitro; amino; or --OZ wherein Z is hydrogen; C.sub.1 -C.sub.4 alkyl; C.sub.2 -C.sub.4 alkenyl; benzyl which may be substituted with halogen, C.sub.1 -C.sub.4 alkyl, nitro, trifluoromethyl, hydroxycarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, or cyano; phenylcarbonylmethyl; pyridylmethyl; phenyl which may be substituted with nitro or halogen; pyridyl or pyrimidyl which may be substituted with nitro; phenylsulfonyl which may be substituted with C.sub.1 -C.sub.4 alkyl; or benzyloxycarbonyl which may be substituted with halogen; n is 4 to 10; and the mark * indicates that the configuration of the carbon may be either one of D-configuration, L-configuration and DL-configuration or a pharmaceutical acceptable salt thereof. This phenylalanine derivative is effective as a proteinase inhibitor.
一种
苯丙
氨酸衍
生物,其
化学式为(I):##
STR1## 其中R1和R2分别为
氢,但两者不能同时为
氢;C1-C8烷基,可能带有羟基,羟基羰基,C1-C4烷
氧羰基,C1-C4烷基
硫醇,C1-C4烷
氧基,
氨基甲酰基,磺
酰胺基,
吡啶基或
苯基,这些可能进一步带有硝基,C1-C4烷
氧基或卤素;C6-C8
环烷基,可能带有羟基,C1-C4烷
氧基,羟基羰基,C1-C4烷
氧羰基或C1-C4烷基;
苯基,可能带有卤素,硝基,三
氟甲基,C1-C4烷
氧基,C1-C4烷基
硫醇,C1-C4烷基羰基,
苯基羰基,羟基羰基,C1-C4烷
氧羰基,
氨基甲酰基,磺
酰胺基,
酰胺基,
吡啶基羰基或C1-C6烷基,这些可能进一步带有C1-C4烷基羰基,羟基羰基或C1-C4烷
氧羰基;
吡啶基,可能带有卤素或C1-C4烷
氧基;
嘧啶基;N-
苄基氮杂
环己烷基;R1和R2可以与其连接的
氮原子形成环状结构,如
吗啉基;
硫代吗啉基;
哌嗪基,可能带有
苯基羰基,
苄基或C1-C4烷基;
吡咯烷基,可能带有羟基羰基或C1-C4烷
氧羰基;和
哌啶基,带有C1-C4烷基,
苯基C1-C4烷基,
苯基羰基或C1-C4烷
氧羰基;X为
氢,硝基,
氨基或-OZ,其中Z为
氢,C1-C4烷基,C2-C4
烯基,
苄基,可能带有卤素,C1-C4烷基,硝基,三
氟甲基,羟基羰基,C1-C4烷
氧羰基或
氰基;
苯基羰
甲基;
吡啶基
甲基;可能带有硝基的
苯基或卤素的
吡啶基或
嘧啶基;可能带有C1-C4烷基的
苯基磺酰基;或可能带有卤素的
苯甲
氧羰基;n为4到10;*表示
碳的构型可以是D-构型,L-构型和DL-构型之一,或其药学上可接受的盐。此
苯丙
氨酸衍
生物对
蛋白酶具有抑制作用。