Inhibitors of oxidized low-density lipoprotein receptor 1 and methods of use thereof

Abstract

Inhibitors of oxidized low-density lipoprotein receptor 1 (LOX-1), compositions comprising inhibitors of LOX-1, and methods of using thereof are described.

1 - 23 . (canceled) 
     
     
         24 . A pharmaceutical composition comprising an effective amount of a compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
       
     
     
         25 - 32 . (canceled) 
     
     
         33 . A method of treating a disorder in a subject in need thereof, the method comprising administering to the subject a compound having a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein n is an integer from 1 to 10; 
         wherein X is selected from oxygen, sulfur, sulfoxide, sulfone, and NH; 
         wherein each of R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 9 , and R 10  is independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, amino, aminoalkyl, phosphoro, sulfhydryl, sulfino, sulfo, and cyano, provided that when Yi is nitrogen, then R 4  is absent and/or that when R 2  is nitrogen, then R 3  is absent; and 
         wherein each occurrence of R 5  is independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxyl, aldehyde, haloformyl, hydroperoxyl, halogen, amino, phosphor, sulfhydryl, sulfino, sulfo, C1-C6 alkyl, and cyano, or a pharmaceutically acceptable salt thereof, wherein the disorder is selected from atherosclerosis, diabetes, hypertension, and dyslipidemia. 
       
     
     
         34 - 39 . (canceled) 
     
     
         40 . The method of  claim 33 , wherein the disorder is atherosclerosis. 
     
     
         41 . The method of  claim 33 , wherein n is an integer from 1 to 6;
 wherein X is selected from oxygen and sulfur;   wherein each of R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 9 , and R 10  is independently selected from hydrogen and halogen; and   wherein each occurrence of R 5  is independently selected from hydrogen, hydroxyl, and alkyloxyl.   
     
     
         42 . The method of  claim 33 , wherein the compound has a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano; 
         wherein R 2  is selected from hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, unsubstituted aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano; 
         wherein R 3  is selected from hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano; 
         wherein R 5  is hydroxyl; and 
         wherein each of R 6 , R 7 , R 8 , R 9 , and R 10  is independently selected from hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, phosphor, sulfhydryl, sulfino, sulfo, and cyano. 
       
     
     
         43 . The method of  claim 42 , wherein X is oxygen. 
     
     
         44 . The method of  claim 42 , wherein R 1  is selected from hydrogen, amino, and C1-C5 alkyl. 
     
     
         45 . The method of  claim 42 , wherein R 2  is selected from hydrogen and C1-C5 alkyl. 
     
     
         46 . The method of  claim 42 , wherein R 3  is selected from hydrogen, C1-C5 alkyl, cyano, and halogen. 
     
     
         47 . The method of  claim 42 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         48 . The method of  claim 42 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         49 . A compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         50 . A pharmaceutical composition comprising an effective amount of a compound having a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each n is independently 1, 2, 3, or 4; and 
         wherein R 1  is a C1-C4 alkyl, 
         or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
       
     
     
         51 . The pharmaceutical composition of  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.