Invention Application
WO2010034649A1 2,3-SUBSTITUTED INDAZOLE OR 4,5,6,7-TETRAHYDRO-INDAZOLES AS FXR MODULATORS AGAINST DYSLIPIDEMIA AND RELATED DISEASES
审中-公开
2,3-取代的吲唑或4,5,6,7-四氢-1H-吲唑作为抗逆转录酶和相关疾病的FXR调节剂
- Patent Title: 2,3-SUBSTITUTED INDAZOLE OR 4,5,6,7-TETRAHYDRO-INDAZOLES AS FXR MODULATORS AGAINST DYSLIPIDEMIA AND RELATED DISEASES
- Patent Title (中): 2,3-取代的吲唑或4,5,6,7-四氢-1H-吲唑作为抗逆转录酶和相关疾病的FXR调节剂
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Application No.: PCT/EP2009/061912Application Date: 2009-09-15
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Publication No.: WO2010034649A1Publication Date: 2010-04-01
- Inventor: BENSON, Gregory Martin , BLEICHER, Konrad , GRETHER, Uwe , KUHN, Bernd , RICHTER, Hans , TAYLOR, Sven
- Applicant: F. HOFFMANN-LA ROCHE AG , BENSON, Gregory Martin , BLEICHER, Konrad , GRETHER, Uwe , KUHN, Bernd , RICHTER, Hans , TAYLOR, Sven
- Applicant Address: Grenzacherstrasse 124 CH-4070 Basel CH
- Assignee: F. HOFFMANN-LA ROCHE AG,BENSON, Gregory Martin,BLEICHER, Konrad,GRETHER, Uwe,KUHN, Bernd,RICHTER, Hans,TAYLOR, Sven
- Current Assignee: F. HOFFMANN-LA ROCHE AG,BENSON, Gregory Martin,BLEICHER, Konrad,GRETHER, Uwe,KUHN, Bernd,RICHTER, Hans,TAYLOR, Sven
- Current Assignee Address: Grenzacherstrasse 124 CH-4070 Basel CH
- Agency: KLOSTERMEYER, Doerte
- Priority: EP08165145.7 20080925
- Main IPC: C07D231/56
- IPC: C07D231/56 ; C07D401/12 ; C07D403/12 ; A61P3/06 ; A61P3/10 ; A61K31/416
Abstract:
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.
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