Thiazole derivatives, their preparation and their use in the treatment of diabetes complications
申请人:Sankyo Company Limited
公开号:EP0337819A1
公开(公告)日:1989-10-18
Compounds of formula (I):
in which:
R1 and R2 are independently hydrogen, alkyl, aliphatic hydrocarbon groups having one or two carbon-carbon double or treble bonds, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, alkanoyl, alkenoyl, cycloalkylcarbonyl, arylcarbonyl, substituted arylcaronyl, arylalkanoyl, substituted arylalkanoyl, arylalkenoyl, substituted arylalkenoyl, alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, aralkyloxycarbonyl, substituted aralkyloxycarbonyl, optionally substituted carbamoyl or thiocarbamoyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl, substituted arylsulphonyl, alkylthio, arylthio and substituted arylthio, or R1 and R2, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group; one of Ra and Rb is hydrogen, alkyl or halogen, and the other of Ra and Rb is a group of formula (II):
R4 is hydrogen, carboxy, protected carboxy or optionally substituted carbamoyl; R5 is hydrogen, or carboxyalkyl or protected carboxyalkyl in which the alkyl part is C1 -Cs; n = 0, 1 or 2; X is oxygen or sulphur;
are useful in the treatment of the complications attendant upon diabetes and may be prepared by condensation of a thiazolidine or rhodanine compound with a compound corresponding to the remainder of the molecule of the compound of formula (I).
式(I)化合物:
其中
R1 和 R2 独立地为氢、烷基、具有一个或两个碳碳双键或三键的脂族烃基、环烷基、芳基、取代芳基、烷酰基、烯酰基、环烷基羰基、芳基羰基、取代芳基羰基、芳基烷酰基、取代芳基烷酰基、芳基烯酰基、取代芳基烯酰基、烷氧基羰基、芳氧基羰基、芳氧基羰基、芳烷氧基羰基、取代芳氧基羰基、芳烷氧基羰基、芳烷氧基羰基、取代芳烷氧基羰基、选择性取代氨基甲酰基或硫代氨基甲酰基、烷氧基羰基、芳氧基羰基、取代的芳氧基羰基、烷氧基羰基、取代的芳氧基羰基、任选取代的氨基甲酰基或硫代氨基甲酰基、烷基磺酰基、卤代烷基磺酰基、芳基磺酰基、取代的芳基磺酰基、烷硫基、芳硫基和取代的芳硫基,或 R1 和 R2 与它们所连接的氮原子一起形成含氮杂环基团;Ra 和 Rb 中的一个是氢、烷基或卤素,Ra 和 Rb 中的另一个是式 (II) 基团:
R4 是氢、羧基、受保护的羧基或任选取代的氨基甲酰基;R5 是氢、羧基烷基或受保护的羧基烷基,其中烷基部分是 C1-Cs;n = 0、1 或 2;X 是氧或硫;
可通过噻唑烷或罗丹宁化合物与对应于式(I)化合物分子剩余部分的化合物缩合制备。