Diacylglycerol acyl transferase 2 inhibitors

Abstract

Compounds of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.

What is claimed is: 
     
         1 . A method for the reduction of at least one point in severity of nonalcoholic fatty liver disease or nonalcoholic steatohepatitis grading scoring systems, reduction of the level of serum markers of nonalcoholic steatohepatitis activity, reduction of nonalcoholic steatohepatitis disease activity or reduction in the medical consequences of nonalcoholic steatohepatitis in humans comprising the step of administering to a human in need of such reduction an effective amount of a compound according to Formula (I) or a pharmaceutically acceptable salt of said compound to a patient in need thereof;
 wherein the compound of Formula (I) is:   
       
         
           
           
               
               
           
         
         wherein
 D 1  and D 2  are each independently N or CH; 
 R 1  is H, or (C 1 -C 2 )alkyl optionally substituted with one or two substituents each independently selected from fluoro and (C 3 -C 6 )cycloalkyl; 
 R 2  is H or fluoro; 
 R 3  is, 
 
       
       
         
           
           
               
               
           
         
         
           R 4  is H, cyano, or (C 1 -C 4 )alkyl optionally substituted with one or two substituents each independently selected from —OH and —S(O) 2 R 6 ; 
           R 5  is H or —OH; and 
           R 6  is (C 1 -C 4 )alkyl. 
         
       
     
     
         2 . A method for treating hyperlipidemia, Type I diabetes, Type II diabetes mellitus, idiopathic Type I diabetes (Type Ib), latent autoimmune diabetes in adults (LADA), early-onset Type 2 diabetes (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, coronary heart disease, ischemic stroke, restenosis after angioplasty, peripheral vascular disease, intermittent claudication, myocardial infarction, dyslipidemia, post-prandial lipemia, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity, osteoporosis, hypertension, congestive heart failure, left ventricular hypertrophy, peripheral arterial disease, diabetic retinopathy, macular degeneration, cataract, diabetic nephropathy, glomerulosclerosis, chronic renal failure, diabetic neuropathy, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, stroke, vascular restenosis, hyperglycemia, hyperinsulinemia, hypertrygliceridemia, insulin resistance, impaired glucose metabolism, erectile dysfunction, skin and connective tissue disorders, foot ulcerations and ulcerative colitis, endothelial dysfunction and impaired vascular compliance, hyper apo B lipoproteinemia, Alzheimer's, schizophrenia, impaired cognition, inflammatory bowel disease, ulcerative colitis, Crohn's disease, and irritable bowel syndrome, non-alcoholic steatohepatitis (NASH), or non-alcoholic fatty liver disease (NAFLD), in humans comprising the step of administering to a human in need of such treatment a therapeutically effective amount of a compound according to Formula (I) or a pharmaceutically acceptable salt of said compound;
 wherein the compound of Formula (I) is:   
       
         
           
           
               
               
           
         
         wherein
 D 1  and D 2  are each independently N or CH; 
 R 1  is H, or (C 1 -C 2 )alkyl optionally substituted with one or two substituents each independently selected from fluoro and (C 3 -C 6 )cycloalkyl; 
 R 2  is H or fluoro; 
 R 3  is, 
 
       
       
         
           
           
               
               
           
         
         
           R 4  is H, cyano, or (C 1 -C 4 )alkyl optionally substituted with one or two substituents each independently selected from —OH and —S(O) 2 R 6 ; 
           R 5  is H or —OH; and 
           R 6  is (C 1 -C 4 )alkyl. 
         
       
     
     
         3 . The method of  claim 1  wherein the method reduces portal hypertension, hepatic protein synthetic capability, hyperbilirubinemia, or encephalopathy.