Antiviral methods and compounds

Abstract

The invention provides a method, compounds, and compositions for inhibiting the replication or proliferation of a virus. In accordance with the invention, at least one cannabichromene derivative is exposed to the virus, a host cell, or an infected cell under conditions sufficient to inhibit the replication or proliferation of the virus.

What is claimed is:  
     
         1 . A cannabichromene derivative having following formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is: a) H, 
 b) a C 1-4  alkyl group or ester thereof,  
 c) COOH,  
 d) OH,  
 e) a O—C 1-5  alkyl (preferably OCH 3 ) or alkanoyl, optionally substituted by mono- or di-methylamino or ethylamino groups,  
 f) a O—CO—C 3-10  alkyl group containing a carboxyl or amino group, g)  
                     
 h) a p-aminobenzyl group or a C 1-7  aminoalkyl group or an organic or mineral acid addition salt thereof, an isocyanate or isothiocyanate derivative of the p-aminobenzyl or aminoalkyl group, a carboxyl terminated derivative of the aminoalkyl group having from 1 to 7 additional carbon atoms or a salt thereof, and an activated derivative of the carboxyl terminated derivative;  
 i) R 1  and R 2  comprise a substituent of the formula —O(CH 2 ) 3-5 , wherein R 1  and R 2 , together with the carbon atoms to which they are bonded, comprises a ring where at least one hydrogen atom thereof is optionally substituted with a halogen (e.g., fluorine, bromine, iodine, astatine);  
 j) a lactone (e.g., COCOH); or  
 k) CH(CH 3 )CO 2 H or —OCOCH 3    
 
 R 2  is: a) H, OH, COOH, or a halogen 
 b) C 1-6  carboxy or alkoxy group, or  
 c) R 1  and R 2  comprise a substituent of the formula —O(CH 2 ) 3-5 , wherein R 1  and R 2 , together with the carbon atoms to which they are bonded, comprises a ring where at least one hydrogen atom thereof is optionally substituted with a halogen.  
 
 R 3  is: a) (W) m -Y-(Z) n , wherein 
 W is a C 5-12  straight or branched (preferably 1′SCH 3-5 , 2R′CH 3  dimethyl) alkyl (e.g., -pentyl, -hexyl, -heptyl, -octyl, or -nonyl), alkenyl, alkynyl, group, or mixture thereof, optionally substituted with at least one halogen (e.g., halogen terminal group or even dihalogen),  
 Y is a bond, O, S, SO, SO 2 , CO, NH, N(C 1-6  alkyl), or NCS,  
 Z is: i) a C 5-12  alkyl, alkenyl, alkynyl, group, or mixture thereof, optionally substituted with at least one halogen, optionally substituted with a terminal aromatic ring, 
 ii) CN 1-3 , CO 2 H, or CO 2 C 1-4  alkyl, CONH 2 , CONHC 1-4  alkyl, or CON(C 1-4  alkyl) 2 , wherein each C 1-4  alkyl on the amide nitrogen can be the same or different, or  
 iii) a phenyl or benzyl group, optionally substituted with halo, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  alkylthio, CN, CF 3 , CO 2 H, or CO 2 C 1-4  alkyl, CONH 2 , CONHC 1-4  alkyl, or CON(C 1-4  alkyl) 2 , wherein each C 1-4  alkyl on the amide nitrogen can be the same or different, and wherein  
 
 m and n are the same or different, and each is either 0 or 1,  
 b) a C 5-12  alkyl or haloalkyl group, optionally substituted with a terminal aromatic ring, CN 1-3 , NCS, CO 2 H, or CO 2 C 1-4  alkyl, CONH 2 , CONHC 1-4  alkyl, or CON(C 1-4  alkyl) 2 , wherein each C 1-4  alkyl on the amide nitrogen can be the same or different, or  
 c) a C 5-12  alkene or alkyne group, optionally substituted with a halogen, dithiolene, terminal aromatic ring, CN 1-3 , NCS, CO 2 H, or CO 2 C 1-4  alkyl, CONH 2 , CONHC 1-4  alkyl, or CON(C 1-4  alkyl) 2 , wherein each C 1-4  alkyl on the amide nitrogen can be the same or different;  
 
 R 6  is selected from the group consisting of: 
 a) hydrogen,  
 b) hydroxy or lactone,  
 c) halo,  
 d) C 1-6  alkoxy, C 1-6  alkylthio, C 1-6  alkyl, or C 1-6  haloalkyl,  
 e) CN,  
 f) N 3 ,  
 g) CO 2 H,  
 h) CO 2 —C 1-4  alkyl,  
 i) C(Y)(Z)-OH,  
 j) C(Y)(Z)-O—C 1-4  alkyl, and  
 k) C 1-6  alkyl-CO 2 —Y,  
 wherein Y and Z are each independently H or C 1-6  alkyl,  
 
 R 7  is selected from the group consisting of: 
 a) hydrogen,  
 b) hydroxy or lactone,  
 c) halo, d) C hd  1 - 6  alkoxy, C 1-6  alkylthio, C 1-6  alkyl, or C 1-6  haloalkyl,  
 e) CN,  
 f)N 3 ,  
 g) CO 2 H,  
 h) CO 2 —C 1-4  alkyl,  
 i) C(Y)(Z)-OH,  
 j) C(Y)(Z)-O—C 1-4  alkyl,  
 k) C 1-6  alkyl-CO 2 —Y, and  
 l) =O or =S;  
 wherein Y and Z are each independently H or C 1-6  alkyl,  
 
 R 12  and R 12′  together form =O or =S, or each is independently selected from the group consisting of: 
 a) hydrogen,  
 b) hydroxy or lactone,  
 c) halo,  
 b) C 1-6  alkoxy, C 1-6  alkylthio, C 1-6  alkyl, or C 1-6  haloalkyl,  
 c) CN,  
 d) N 3 ,  
 d) CO 2 H,  
 e) CO 2 —C 1-4  alkyl,  
 f) C(Y)(Z)-OH,  
 g) C(Y)(Z)-O—C 1-4  alkyl, and  
 h) C 1-6  alkyl-CO 2 —Y,  
 wherein Y and Z are each independently H or C 1-6  alkyl; and  
 
 Q is: a) O or S, or 
 b) N-W, wherein W is: 
 i) hydrogen,  
 ii) C 1-6  alkoxyalkyl, C 1-6  alkyl, or C 1-6  haloalkyl  
 iii) OC 1-6  alkyl, or OC 1-6  haloalkyl,  
 iv) CN,  
 v) C 1-6  alkyl,  
 vi) C(Y)(Z)C 1-4  alkyl, or  
 vii) C 1-6  alkyl-CO 2 -Z,  
 
 wherein Y and Z are each independently H or C 1-6  alkyl.  
 
 
     
     
         2 . The cannabichromene derivative of  claim 1 , wherein R 1  is a lactone, H, methyl, OCH 3 , —CH(CH 3 )CO 2 H, or —OCOCH 3 ;  
     
     
         3 . The cannabichromene derivative of  claim 1 , wherein R 2  is: a halogen, H or COOH.  
     
     
         4 . The cannabichromene derivative of  claim 1 , wherein R 3  is: a C 5-12  alkyl; haloalkyl, alkenyl, haloalkenyl, alkynyl, or haloalkynyl, group, or mixture thereof;  
     
     
         5 . The cannabichromene derivative of  claim 1 , wherein R 3  is 1,1,5-trimethylhexyl, 1,1,5,5-tetramethylhexyl, or 1,1,5-trimethyl-hept-4-enyl.  
     
     
         6 . The cannabichromene derivative of  claim 1 , wherein R 6  is H, OH, lactone, halogen, C 1-6  alkoxy, or C 1-6  alkyl.  
     
     
         7 . The cannabichromene derivative of  claim 1 , wherein R 7  is H, OH, halogen, or COOH.  
     
     
         8 . The cannabichromene derivative of  claim 1 , wherein R 12  is H, OH, lactone, halogen, C 1-6  alkoxy, or C 1-6  alkyl.  
     
     
         9 . The cannabichromene derivative of  claim 1 , wherein R 12′  is H, OH, lactone, halogen, C 1-6  alkoxy, or C 1-6  alkyl.  
     
     
         10 . The cannabichromene derivative of  claim 1 , wherein Q is oxygen.  
     
     
         11 . The cannabichromene derivative of  claim 1 , wherein the bond between C7 and C8 is a double bond.  
     
     
         12 . The cannabichromene derivative of  claim 1 , wherein R 6  is CH 3 , R 7  is H, R 12  and R 12′  are each CH 3 , Q is oxygen, and the bond between C7 and C8 is a double bond.  
     
     
         13 . An antiviral composition comprising the cannabichromene derivative of claim  15  and an agriculturally-acceptable carrier.  
     
     
         14 . A pharmaceutical composition comprising the cannabichromene derivative of claim  15  and a pharmacologically-acceptable carrier.