申请人:Cell Therapeutics, Inc.
公开号:US05473070A1
公开(公告)日:1995-12-05
There is disclosed compounds and pharmaceutical compositions comprising compounds of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 7 to 20, at least one of X or Y is --OH and if one of X or Y is --OH then the other X or Y is H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and W.sub.1, W.sub.2, and W.sub.3 is independently H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and wherein the alkyl groups may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers, salts and mixtures thereof. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
本发明涉及化合物和制药组合物,其包括以下结构的化合物:##STR1## 其中一个或两个R中的每一个独立地是##STR2## 其中n是从7到20的整数,X或Y中至少一个是--OH,如果X或Y中的一个是--OH,则另一个X或Y是H,CH.sub.3,CH.sub.3 --CH.sub.2,CH.sub.3 --(CH.sub.2).sub.2 --或(CH.sub.3).sub.2 --CH.sub.2 --,W.sub.1,W.sub.2和W.sub.3独立地是H,CH.sub.3,CH.sub.3 --CH.sub.2,CH.sub.3 --(CH.sub.2).sub.2 --或(CH.sub.3).sub.2 --CH.sub.2 --,其中烷基基团可以被羟基,卤素或二甲氨基基团取代和/或由氧原子,H或烷基(1-4C)中断,包括已分离的对映异构体和/或二面体异构体,盐和混合物。特别地,这些化合物在主要刺激和它们与细胞接触的几秒钟内降低了源自所述PA的不饱和非花生四烯酸磷脂酸(PA)和二酰基甘油(DAG)的升高水平。调节作用取决于目标细胞的性质和施加的刺激。