发明公开
EP2344459A1 2,3-SUBSTITUTED INDAZOLE OR 4,5,6,7-TETRAHYDRO-INDAZOLES AS FXR MODULATORS AGAINST DYSLIPIDEMIA AND RELATED DISEASES
有权
2,3-取代的4,5,6,7-吲唑或TETRAHYDROINDAZOLE AS调节剂的FXR AGAINST血脂异常和相关疾病
- 专利标题: 2,3-SUBSTITUTED INDAZOLE OR 4,5,6,7-TETRAHYDRO-INDAZOLES AS FXR MODULATORS AGAINST DYSLIPIDEMIA AND RELATED DISEASES
- 专利标题(中): 2,3-取代的4,5,6,7-吲唑或TETRAHYDROINDAZOLE AS调节剂的FXR AGAINST血脂异常和相关疾病
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申请号: EP09783005.3申请日: 2009-09-15
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公开(公告)号: EP2344459A1公开(公告)日: 2011-07-20
- 发明人: BENSON, Gregory Martin , BLEICHER, Konrad , GRETHER, Uwe , KUHN, Bernd , RICHTER, Hans , TAYLOR, Sven
- 申请人: F. Hoffmann-La Roche AG
- 申请人地址: Grenzacherstrasse 124 4070 Basel CH
- 专利权人: F. Hoffmann-La Roche AG
- 当前专利权人: F. Hoffmann-La Roche AG
- 当前专利权人地址: Grenzacherstrasse 124 4070 Basel CH
- 代理机构: Salud, Carlos E.
- 优先权: EP08165145 20080925
- 国际公布: WO2010034649 20100401
- 主分类号: C07D231/56
- IPC分类号: C07D231/56 ; C07D401/12 ; C07D403/12 ; A61P3/06 ; A61P3/10 ; A61K31/416
摘要:
This invention relates to novel indazole or 4,5,6,7-tetrahydro-indazole derivatives of formula (I) wherein R
1 to R
8 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are FXR modulators and can be used as medicaments. The compounds are selective modulators of the farnesoid-X-receptor, preferably agonists. The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily of transcription factors. Diseases which are affected by FXR modulators include increased lipid and cholesterol levels, particularly high LDL-cholesterol, high triglycerides, low HDL-cholesterol, dyslipidemia, diseases of cholesterol absorption, atherosclerotic disease, peripheral occlusive disease, ischemic stroke, diabetes, particularly non-insulin dependent diabetes mellitus, metabolic syndrome, diabetic nephropathy, obesity, cholesterol gallstone disease, cholestasis/fibrosis of the liver, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), psoriasis, cancer, particularly gastrointestinal cancer, osteoporosis, Parkinson's disease and Alzheimer's disease. Preferred diseases (and conditions) which are affected by FXR modulators are prevention or treatment of high LDL cholesterol levels, high triglycerides, dyslipidemia, cholesterol gallstone disease, cancer, non-insulin dependent diabetes mellitus and metabolic syndrome. Particularly preferred diseases which arc affected by FXR modulators arc high LDL cholesterol, high triglyceride levels and dyslipidemia.
1 to R
8 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are FXR modulators and can be used as medicaments. The compounds are selective modulators of the farnesoid-X-receptor, preferably agonists. The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily of transcription factors. Diseases which are affected by FXR modulators include increased lipid and cholesterol levels, particularly high LDL-cholesterol, high triglycerides, low HDL-cholesterol, dyslipidemia, diseases of cholesterol absorption, atherosclerotic disease, peripheral occlusive disease, ischemic stroke, diabetes, particularly non-insulin dependent diabetes mellitus, metabolic syndrome, diabetic nephropathy, obesity, cholesterol gallstone disease, cholestasis/fibrosis of the liver, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), psoriasis, cancer, particularly gastrointestinal cancer, osteoporosis, Parkinson's disease and Alzheimer's disease. Preferred diseases (and conditions) which are affected by FXR modulators are prevention or treatment of high LDL cholesterol levels, high triglycerides, dyslipidemia, cholesterol gallstone disease, cancer, non-insulin dependent diabetes mellitus and metabolic syndrome. Particularly preferred diseases which arc affected by FXR modulators arc high LDL cholesterol, high triglyceride levels and dyslipidemia.
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