Indole Antiviral Compositions And Methods

Abstract

The present invention provides novel chemical compounds, and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

1 . A composition comprising a compound as depicted in formula (I), wherein formula (I) is as follows: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is alkyl C 1-10 ; alkenyl C 1-10 ; aryl C 1-10 , including heteroaryl; HEM (hydroxyethoxymehtoxy), DHPM (dihydroxypropoxymethyl); pentofuranosyl and pentopyranosyl (D or L) (α or β), tetrafuranosyl (D or L) (α or β); 
 R 2  is —NR 8 R 9  where R 8  and R 9  may be different or the same and selected from alkyl (C 1-10 ), alkenyl (C 1-10 ), aryl, heteroaryl, arylalkyl; halogen, cyano, mercaptan, alkylmercaptan, (C 1-10 ), or alkoxy (C 1-10 ); 
 R 3  is cyano; C═NR 12  where R 12  may be alkyl, alkylamine, urea, thiourea; —CXNH 2  where X may be ═S, ═O, ═NH, ═N—NH 2 , ═NOH, ═N—NHR; —RC═O where R may be H, alkyl (C 1-10 ); —CH 2 —C—R where R may be H, alkyl (C 1-10 ); heterocycle, thiophine, furan, imidazole, tetrazole, imidazolidine, thiazole, triazole; or nitro; and 
 R 4 -R 7  are halogens where R 4 -R 7  may be the same or different halo groups or hydrogen; R 4 -R 7  may be nitro groups or azido group with halogens in different juxtapositions, or R 4 -R 7  may also represent different alkyl (C 1-6 ) groups in with the halogens, nitro and azido groups. 
 
     
     
         2 . The composition of  claim 1 , wherein said compound is selected from the group consisting of compound 4.33, compound 4.46, compound 4.97, compound 4.117, compound 4.122, compound 4.137, 4.140, and compound 4.143. 
     
     
         3 . The composition of  claim 1 , wherein in said compound is selected from compounds 4.117 and 4.143. 
     
     
         4 . The composition of  claim 1 , wherein said compound has antiviral activity. 
     
     
         5 . The composition of  claim 4 , wherein said compound has a selectivity index of at least 85. 
     
     
         6 . The composition of  claim 1 , further comprising a pharmaceutically acceptable carrier or a pharmaceutically acceptable derivative. 
     
     
         7 . A composition comprising a compound as depicted in formula (I), wherein formula (I) is as follows: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is i) a molecule selected from: D or L-ribose, D or L-xylose, D or L-arabinose, D or L-lyxose, D or L-erythrose, D or L threose; ii) the 2-deoxy, 3-deoxy, 5-deoxy, 5-O-acetyl, and 2,3-dideoxy derivatives of said molecules; iii) the α or β-anomers of said molecules and said derivatives; iv) alkyl (C 1-10 ); v) aralkyl; vi) heteroaryl; vii) HEM (hydroxyethoxymethoxy), DHPM (dihydroxypropoxymethyl); viii) or structural variations of HEM & DHPM; 
 R 2  is NR 8 R 9  where R 8 ═R 9 H, CH 3 , C 2 H 5  isopropyl, cyclopropyl; halogen, chloro, bromo; —O—R 10  where R 10 ═CH 3 , C 2 H 5 , CH 2 C 6 H 5 ; —S—R 11  where R 11 ═H, CH 3 , C 2 H 5 , or CH 2 C 6 H 5 ; 
 R 3  is cyano; C═NR 12  where R 12  is urea, substituted urea, thiourea, substituted thiourea; 
 CXNH 2  where X is ═O, ═S, ═NOH, ═N—NH 2 ; —CR═O where R is H, CH 3 , C 2 H 5 , C 3 H 7 ; —CH 2 —RC═O where R is H, CH 3 , C 2 H 5 , C 3 H 7 ; or exocyclic heterocycles; and 
 R 4 -R 7  are selected variations of substitution using the halo groups Cl, Br, F or I and the nitro and azido groups. 
 
     
     
         8 . The composition of  claim 7 , wherein said compound is selected from the group consisting of compound 4.33, compound 4.46, compound 4.97, compound 4.117, compound 4.122, compound 4.137, 4.140, and compound 4.143. 
     
     
         9 . The composition of  claim 7 , wherein in said compound is selected from compounds 4.117 and 4.143. 
     
     
         10 . The composition of  claim 7 , wherein said compound has antiviral activity. 
     
     
         11 . The composition of  claim 10 , wherein compound has a selectivity index of at least 85. 
     
     
         12 . The composition of  claim 7 , further comprising a pharmaceutically acceptable carrier or a pharmaceutically acceptable derivative. 
     
     
         13 . A composition comprising a compound as depicted in formula (I), wherein formula (I) is as follows: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is D-ribofuranosyl, 2′-deoxy-D-ribofuranosyl, 5′-O-acetyl-D-ribofuranosyl, 5′-O-acetyl-2′-deoxy-D-ribofuranosyl, 2′,3′,5′-tri-O-acetyl-D-ribofuranosyl, 3′-5′-di-O-acetyl-2′-deoxy-D-ribofuranosyl; or 5′-deoxy-D-ribofuranosyl, 2′,3′-di-O-acetyl-5′-deoxy-D-ribofuranosyl; 
 R 2  is —NR 8 R 9  where R 8 ═R 9 ═H, CH 3 , C 2 H 5 , R 8 ═H R 9 =isopropyl or cyclopropyl; where R 2 ═Cl, Br; 
 R 3  is cyano; C═NR 12  where R 12 =urea, thiourea; —CXNH 2  where X is ═O, ═S, ═NOH, ═N—HN—R; —RC═O where R═H, CH 3 , C 2 H 5 , C 3 H 7 ; thienyl, or furyl; and 
 R 4 -R 7  are exocyclic groups selected from chloro, bromo, hydrogen or nitro groups. 
 
     
     
         14 . The composition of  claim 13 , wherein said compound is selected from the group consisting of compound 4.33, compound 4.46, compound 4.97, compound 4.117, compound 4.122, compound 4.137, 4.140, and compound 4.143. 
     
     
         15 . The composition of  claim 13 , wherein in said compound is selected from compounds 4.117 and 4.143. 
     
     
         16 . The composition of  claim 13 , wherein said compound has antiviral activity. 
     
     
         17 . The composition of  claim 16 , wherein said compound has a selectivity index of at least 85. 
     
     
         18 . The composition of  claim 13 , further comprising a pharmaceutically acceptable carrier or a pharmaceutically acceptable derivative.