Benzoxazepine compounds, their production and use

Abstract

This invention provides new benzoxazepine compounds represented by the formula: [wherein R stands for a lower alkyl group optionally substituted with a hydroxyl group, X stands for an optionally substituted carbamoyl group or an optionally substituted heterocyclic group having a deprotonatable hydrogen atom, R 1 stands for a lower alkyl group and W stands for a halogen atom] having activities of lowering cholesterol-level and lowering triglyceride-level, and being useful for prophylaxis and therapy of hyperlipidemia.

1 - 36 . (canceled)  
     
     
         37 . A composition comprising: 
 N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof; and    one or more agents for controlling the biosynthesis of cholesterol.    
     
     
         38 . A composition as claimed in  claim 37  further comprising a pharmaceutically acceptable carrier.  
     
     
         39 . A composition as claimed in  claim 37  wherein the one or more agents for controlling the biosynthesis of cholesterol are HMG-CoA reductase inhibiting agents.  
     
     
         40 . A composition as claimed in  claim 39  wherein the HMG-CoA reductase inhibiting agent is a statin.  
     
     
         41 . A composition as claimed in  claim 39  wherein the HMG-CoA reductase inhibiting agent is selected from the group consisting of lovastatin, simvastatin and pravastatin.  
     
     
         42 . A composition comprising: 
 N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof;    one or more agents for controlling the biosynthesis of cholesterol selected from the group consisting of lovastatin, simvastatin and pravastatin; and    a pharmaceutically acceptable carrier.    
     
     
         43 . A method for preparation of a pharmaceutical composition comprising admixing the composition of  claim 37  with a pharmaceutically acceptable carrier.  
     
     
         44 . A method for prophylaxis or therapy of hyperlipidemia in a mammal comprising administering an effective amount of N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof, in combination with one or more agents for controlling the biosynthesis of cholesterol in said mammal.  
     
     
         45 . A method for lowering the lipid-level in a mammal comprising administering an effective amount of N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof, in combination with one or more agents for controlling the biosynthesis of cholesterol in said mammal.  
     
     
         46 . A method for lowering the level of triglyceride in a mammal comprising administering an effective amount of N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof, in combination with one or more agents for controlling the biosynthesis of cholesterol in said mammal.  
     
     
         47 . The method of any one of claims  44 ,  45  or  46  wherein the one or more agents for controlling the biosynthesis of cholesterol in said mammal are HMG-CoA reductase inhibiting agents.  
     
     
         48 . The method of  claim 47  wherein the HMG-CoA reductase inhibiting agent is a statin.  
     
     
         49 . The method of  claim 47  wherein the HMG-CoA reductase inhibiting agents are selected from the group consisting of lovastatin, simvastatin and pravastatin.  
     
     
         50 . A method for controlling the biosynthesis of cholesterol in a mammal comprising administering an effective amount of N-[(3R,5S)-1-(3-Acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-acetic acid, or a salt thereof, in combination with one or more agents selected from the group consisting of lovastatin, simvastatin and pravastatin.