申请人:SUMITOMO PHARMACEUTICALS COMPANY, LIMITED
公开号:EP0292305A1
公开(公告)日:1988-11-23
Thiazolidin-4-one derivatives are represented by the following general formula (I)
wherein.
R1 and R2 are the same or different and denote each
(i) a residue represented by the general formula -A-R4
wherein, A denotes a single bond, C1-C8 alkylene, C2-C8 alkenylene, or C2-C8 alkynylene and R4 denotes hydrogen, C1-C12 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl, or C1-C6 haloalkyl, or
(ii) a residue represented by the general formula
wherein, B denotes a single bond or C1-C6 alkylene, R5 denotes hydrogen, C1-C6 alkyl, C2-Cs alkenyl, C3-C8 cycloalkyl, substituted silyl, or substituted or unsubstituted aryl, n and n' denote each an integer of 2 to 4, m denotes an integer of 1 to 3, and m' denotes an integer of 0 to 2; and
R3 denotes hydrogen, C1-C2 alkyl, allyl, 2-propynyl, or a residue represented by
(a) the general formula
wherein, R6 denotes halogen, an aryl group substituted or unsubstituted by one or more hydroxy or C1-C4 alkoxy groups, or a residue represented by the general formula -D-R7 (D denotes oxygen or sulfur and R7 denotes hydrogen, C1-C4 alkyl, or Ci-C4 alkanol) and ℓ denotes an integer of 2 to 4,
(b) the general formula
wherein, E denotes oxygen, sulfur, imino, or C1-C4 alkylimino, Ra denotes hydrogen or C1-C4 alkyl, or -(E-R8) denotes a 5- to 7-membered cyclic amino group which optionally contains other hetero atoms, and k denotes an integer of 1 to 3, or
(c) the general formula -F-R9
wherein, F denotes C2-C6 alkylene and R9 denotes a nitrogen-containing heterocyclic aromatic residue or an amino group represented by the general formula
(R10 denotes hydrogen, C1-C4 alkyl, or C1-C4 alkyl or R10 in combination with R11 denotes a 5- to 7-membered cyclic amino group which optionally contains other hetero atoms), with the proviso that, when R1 is hydrogen and
R2 is methyl, R3 denotes hydrogen, Ci-C2 alkyl, 2-propynyl, or a residue represented by
(a) the general formula
wherein, R6 denotes halogen, an aryl group substituted or unsubstituted by one or more hydroxy or C1-C4 alkoxy groups, or a residue represented by the general formula -D-R7 (D denotes oxygen or sulfur and R7 denotes hydrogen, C1-C4 alkyl, or C1-C4 alkanoyl) and ℓ denotes an integer of 2 to 4,
(b) the general formula
wherein, E denotes oxygen, sulfur, imino, or C1-C4 alkylimino, denotes hydrogen or C1-C4 alkyl, or -(E-R8) denotes a 5- to 7-membered cyclic amino group which optionally contains other hetero atoms, and k denotes an integer of 1 to 3, or
(c) the general formula -F-R9
wherein, F denotes C2-C6 alkylene and R9 denotes a nitrogen-containing heterocyclic aromatic residue or an amino group represented by the general formula
(R10 denotes hydrogen, C2-C4 alkyl or C1-C4 alkanoyl and R11 denotes hydrogen or C1-C4 alkyl or R10 in combination with R11 denotes a 5- to 7-membered cyclic amino group which optionally contains other hetero atoms.
Since these derivatives, and acid addition salts thereof have selective PAF-antagonistic activities, these compounds are very useful as preventive and curative agents for PAF-induced diseases, for example, various kinds of inflamation, allergic diseases, circulatory diseases, and gastro-intestinal diseases.
噻唑烷-4-酮衍生物由以下通式 (I) 表示
其中
R1 和 R2 相同或不同,并分别表示
(i) 通式-A-R4 所代表的残基
其中,A 表示单键、C1-C8 亚烷基、C2-C8 亚烯基或 C2-C8 亚炔基,R4 表示氢、C1-C12 烷基、C2-C8 亚烯基、C3-C8 环烷基或 C1-C6 卤代烷基,或
(ii) 由通式表示的残基
其中,B 表示单键或 C1-C6 亚烷基,R5 表示氢、C1-C6 烷基、C2-Cs 烯基、C3-C8 环烷基、取代的硅烷基或取代或未取代的芳基,n 和 n'分别表示 2 至 4 的整数,m 表示 1 至 3 的整数,m'表示 0 至 2 的整数;以及
R3 表示氢、C1-C2 烷基、烯丙基、2-丙炔基或由以下各项表示的残基
(a) 通式
其中,R6 表示卤素、被一个或多个羟基或 C1-C4 烷氧基取代或未取代的芳基,或通式 -D-R7 所代表的残基(D 表示氧或硫,R7 表示氢、C1-C4 烷基或 Ci-C4 烷醇),ℓ 表示 2 至 4 的整数、
(b) 通式
其中,E 表示氧、硫、亚氨基或 C1-C4 烷基亚氨基,Ra 表示氢或 C1-C4 烷基,或-(E-R8) 表示可选含有其他杂原子的 5 至 7 元环状氨基,且 k 表示 1 至 3 的整数,或
(c) 通式-F-R9
其中,F 表示 C2-C6 亚烷基,R9 表示含氮杂环芳香残基或由通式表示的氨基
(R10表示氢、C1-C4 烷基或 C1-C4 烷基,或 R10 与 R11 结合表示可选择含有其他杂原子的 5 至 7 元环状氨基),但条件是,当 R1 为氢且
R2为甲基时,R3表示氢、Ci-C2烷基、2-丙炔基或由以下各项代表的残基
(a) 通式
其中,R6 表示卤素,被一个或多个羟基或 C1-C4 烷氧基取代或未取代的芳基,或通式 -D-R7 所代表的残基(D 表示氧或硫,R7 表示氢、C1-C4 烷基或 C1-C4 烷酰基),ℓ 表示 2 至 4 的整数、
(b) 通式
其中,E 表示氧、硫、亚氨基或 C1-C4 烷基亚氨基,表示氢或 C1-C4 烷基,或-(E-R8)表示可选含有其他杂原子的 5 至 7 元环氨基,且 k 表示 1 至 3 的整数,或
(c) 通式-F-R9
其中,F 表示 C2-C6 亚烷基,R9 表示含氮杂环芳香残基或通式-F-R9 所代表的氨基。
(R10 表示氢、C2-C4 烷基或 C1-C4 烷酰基,R11 表示氢或 C1-C4 烷基,或 R10 与 R11 结合表示 5 至 7 元环状氨基,该氨基可选择含有其他杂原子。
由于这些衍生物及其酸加成盐具有选择性 PAF 拮抗活性,因此这些化合物作为 PAF 引起的疾病(例如各种炎症、过敏性疾病、循环系统疾病和胃肠道疾病)的预防和治疗药物非常有用。