Inhibitors of positive strand rna viruses

Abstract

Methods of treating a disease caused by a positive strand RNA virus. The methods include administering to a subject in need thereof an effective amount of a compound of Formula I.

What is claimed is: 
     
         1 . A method of treating a disease caused by a positive strand RNA virus, the method comprising:
 identifying a subject suffering from the disease, and   administering to the subject an effective amount of a compound of Formula I:   
       
         
           
           
               
               
           
         
       
       wherein
 each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 , independently, is H, halo, alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, OH, alkoxy, carbonyloxy, or amino; 
 each of R 16  and R 17 , independently, is H, halo, alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, OH, alkoxy, carbonyloxy, or amino, or R 16  and R 17  together are a single bond; 
 each of   and  , independently, is a single bond or a double bond; and 
 n is 1, 2 or 3, 
 
       provided that when   is a single bond, X is C═O or CR′R″ and Y is N or N + →O − , and when   is a double bond, X is CR′, Y is N + , and a counterion coexists in the compound, each of R′ and R″, independently, being H, halo, alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, OH, alkoxy, or amino. 
     
     
         2 . The method of  claim 1 , wherein the positive strand RNA virus is a flavivirus or a coronavirus. 
     
     
         3 . The method of  claim 1 , wherein the positive strand RNA virus is a SARS-CoV-2 virus, a Zika virus, a Dengue virus, a HCoV-OC43 virus, or a HCoV-229E virus. 
     
     
         4 . The method of  claim 2 , wherein the positive strand RNA virus is a Zika virus or a Dengue virus. 
     
     
         5 . The method of  claim 2 , wherein the positive strand RNA virus is a SARS-CoV-2 virus. 
     
     
         6 . The method of  claim 1 , wherein each of R 1 , R 5 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15  is H. 
     
     
         7 . The method of  claim 1 , wherein each of R 2 , R 3 , R 6 , and R 7 , independently, is alkoxy. 
     
     
         8 . The method of  claim 1 , wherein R 4  is H or alkoxy. 
     
     
         9 . The method of  claim 1 , wherein R 16  and R 17  together are a single bond. 
     
     
         10 . The method of  claim 1 , wherein X is CH 2 . 
     
     
         11 . The method of  claim 1 , wherein Y is N or N+→O—. 
     
     
         12 . The method of  claim 1 , wherein each of   and   is a single bond. 
     
     
         13 . The method of  claim 1 , wherein n is 1 or 2. 
     
     
         14 . The method of  claim 6 , wherein each of R 2 , R 3 , R 6 , and R 7 , independently, is methoxy and R 4  is H or alkoxy. 
     
     
         15 . The method of  claim 14 , wherein R 16  and R 17  together are a single bond, X is CH 2 , and Y is N or N+→O—. 
     
     
         16 . The method of  claim 1 , wherein each of R 1 , R 5 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15  is H; each of R 2 , R 3 , R 6 , and R 7 , independently, is alkoxy; R 4  is H or alkoxy; R 16  and R 17  together are a single bond; X is CH 2 ; Y is N or N+→O—; each of   and   is a single bond; and n is 1 or 2. 
     
     
         17 . The method of  claim 1 , wherein the compound of Formula I is selected from the group consisting of Compound 1, Compound 4, and Compound 6: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 17 , wherein the positive strand RNA virus is a SARS-CoV-2 virus, a Zika virus, a Dengue virus, a HCoV-OC43 virus, or a HCoV-229E virus. 
     
     
         19 . The method of  claim 17 , wherein the positive strand RNA virus is a Zika virus or a Dengue virus. 
     
     
         20 . The method of  claim 17 , wherein the positive strand RNA virus is a SARS-CoV-2 virus.