申请人:Boehringer Mannheim GmbH
公开号:US04927814A1
公开(公告)日:1990-05-22
The present invention provides disphosphonates of the general formula: ##STR1## wherein R.sub.1 is a straight-chain or branched, saturated or unsaturated aliphatic hydrocarbon radical of 1-9 carbon atoms which is optionally substituted by phenyl or cyclohexyl, R.sub.2 is cyclohexyl or cyclohexylmethyl, benzyl or a straight-chained or branched, saturated or unsaturated aliphatic hydrocarbon of 4 to 18 carbon atoms which is optionally substituted by phenyl or oxygen wherein the oxygen can be esterified or etherified, R.sub.3 is hydrogen or a straight-chain or branched alkyl of 1-4 carbon atoms, X is a straight-chain or branched alkylene chain of 1-6 carbon atoms and Y is hydrogen, hydroxyl or an amino group optionally substituted by alkyl radicals of 1-6 carbon atoms; as well as the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these diphosphonic acid derivatives and pharmaceutical compositions containing them for the prophyllaxis treatment of diseases or disturbances of calcium metabolism such as osteoporsis, Pagets disease, Bechterew's disease, bone metastases, urolithiasis, heterotropic ossifications, rheumatoid arthritis, osteoarthritis and degenerative arthrosis.
本发明提供了一般式为:##STR1## 的二膦酸盐,其中 R.sub.1 是1-9个碳原子的直链或支链、饱和或不饱和的脂肪烃基,可选择地被苯基或环己基取代,R.sub.2 是环己基或环己基甲基、苄基或4至18个碳原子的直链或支链、饱和或不饱和的脂肪烃,可选择地被苯基或氧取代,其中氧可以酯化或醚化,R.sub.3 是氢或1-4个碳原子的直链或支链烷基,X 是1-6个碳原子的直链或支链烷基链,Y 是氢、羟基或氨基,可选择地被1-6个碳原子的烷基基团取代;以及其药理学上可接受的盐。本发明还提供了制备这些二膦酸衍生物的方法以及含有它们的药物组合物,用于预防和治疗钙代谢相关疾病或紊乱,如骨质疏松症、帕盖特氏病、贝克特瑙氏病、骨转移、泌尿结石、异位骨化、类风湿性关节炎、骨关节炎和退行性关节炎。