5-thia-&ohgr;-substituted phenyl-prostaglandin E derivatives, process for producing the same and drugs containing the same as the active ingredient
申请人:Ono Pharmaceutical Co., Ltd.
公开号:US06462081B1
公开(公告)日:2002-10-08
The present invention relates to 5-thia-&ohgr;-substituted phenylprostaglandin E derivatives of the formula (I)
(wherein, all the symbols are as defined in the specification), process for producing them and pharmaceutical compositions comprising them as active ingredient.
The compounds of the formula (I) can bind to PGE2 receptors (especially, subtype EP4) strongly, so they are expected to be useful for prevention and/or treatment of immunological diseases (autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjoegren's syndrome, chronic rheumarthrosis and systemic lupus erythematosus etc., and rejection after organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, lung failure, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardiac ischemia, systemic inflammatory response syndrome, ambustion pain, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, and shock etc. Further, it is thought that EP4 subtype receptor relates to sleeping disorder and blood platelet aggregation, so the compounds of the present invention are expected to be useful for the prevention and/or treatment of such diseases.
本发明涉及公式(I)的5-硫代-ω-取代苯基前列腺素E衍生物(其中,所有符号如规范中所定义),其制备过程以及包含它们作为活性成分的制药组合物。公式(I)的化合物可以强烈结合到PGE2受体(特别是亚型EP4),因此它们被期望用于预防和/或治疗免疫性疾病(自身免疫性疾病,如肌萎缩侧索硬化症(ALS),多发性硬化症,Sjoegren综合症,慢性风湿性关节炎和系统性红斑狼疮等,以及器官移植后的排斥等),哮喘,异常骨形成,神经元细胞死亡,肺衰竭,肝损伤,急性肝炎,肾炎,肾功能不全,高血压,心肌缺血,全身性炎症反应综合征,烧伤疼痛,败血症,血液嗜酸细胞综合征,巨噬细胞激活综合征,Still病,川崎病,烧伤,全身性肉芽肿病,溃疡性结肠炎,克罗恩病,透析时的高细胞因子血症,多器官功能衰竭和休克等。此外,EP4亚型受体与睡眠障碍和血小板聚集有关,因此本发明的化合物被期望用于预防和/或治疗此类疾病。