Compounds, compositions and methods for preventing and treating pestivirus infection and associated diseases

Abstract

Triazinoindole derivatives are useful in the prophylaxis and treatment of pestivirus infections and diseases associated with pestivirus infections.

What is claimed is:  
     
         1 . A compound for treating or preventing pestivirus infection in a mammalian host having or susceptible to said infection, said compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein A represents a substituent selected from the group consisting of: 
 (a) NR 1 R 2  wherein R 1  and R 2  are radicals independently selected from the group consisting of H, straight or branched chain alkyl groups (C 1 -C 6 ), substituted or unsubstituted aryl groups, substituted or unsubstituted aralkyl groups in which the alkyl group is C 1 -C 6 , alkoxy groups (C 1 -C 6 ), acyl groups (C 1 -C 7 ), substituted or unsubstituted carbalkoxy groups (C 1 -C 8  alkoxy), or R 1  and R 2 , together with the nitrogen atom to which they are attached, represent a substituted or unsubstituted heterocyclic ring selected from the group consisting of benzopyridazine, indole, benzotriazole, hexamethyleneimine, imidazole, isoxazole, morpholine, phthalimide, piperidine, piperazine and pyrrolidine;  
 (b) a substituted or unsubstituted heterocyclic group selected from the group consisting of pyridine, benzimidazole, benzodioxane, benzofurazan, indole, benzothiophene, coumarin, furan, hexamethyleneimine, isoxazole, oxadiazole, piperazine, piperidine, pyridine, pyrimidine, pyrrolidine, quinoline, quinuclidene, tetrahydropyran and thiazole;  
 (c) a substituted or unsubstituted phenyl group; and  
 (d) OR 3 , wherein R 3  represents a radical selected from the group consisting of H, a straight or branched chain alkyl (C 1 -C 6 ) group, a substituted or unsubstituted phenyl group a substituted or unsubstituted phenylalkyl group wherein the alkyl group is C 1 -C 6 , or a substituted or unsubstituted tetrahydropyran; Q represents a linking moiety selected from the group consisting of -[(A′) n -(CO)] p —, —S—, —(SO)—, —(SO 2 )— or a valence bond, A′ being —NR a — or —O— and R a  being H or alkyl (C 1 -C 6 ); R b , R c  and R d  independently represent H, alkyl (C 1 -C 4 ), substituted or unsubstituted phenyl or COOR, R being hydrogen or alkyl (C 1 -C 6 ); m is an integer from 0 to 6; n and p independently represent 0 or 1; and q and r are independently integers from 0 to 4; said phenyl, aryl, aralkyl, carbalkoxy and heterocyclic substituents and the W, X, Y and Z substituents being selected from the group consisting of H, alkyl (C 1 -C 6 ), substituted or unsubstituted aryl (C 6 -C 15 ), substituted or unsubstituted aralkyl (C 7 -C 15 ), halogen, CF 3 , CN, O-alkyl (C 1 -C 6 ), acyloxy (C 1 -C 6  acyl), S-alkyl (C 1 -C 6 ), SO-alkyl (C 3 -C 6 ), SO 2 -alkyl (C 1 -C 6 ), NH 2 SO 2 , NO 2 , NH 2 , NHR′, NR′R″, alkyl COOR′, COOR′, alkyl CONR′R″, CONR′R″,  
                     
 R′ and R″ being independently selected from the group consisting of hydrogen or alkyl (C 1 -C 6 ), and the isomers and pharmaceutically acceptable salts of said compound.  
 
     
     
         2 . A compound as claimed in  claim 1 , wherein A represents NR 1 R 2 , R 1  and R 2  being the same or different straight or branched chain alkyl groups (C 1 -C 6 ), or R 1  and R 2 , together with the nitrogen atom to which they are attached being a substituted or unsubstituted heterocyclic ring having from 5 to 9 ring atoms, with nitrogen being the only heteroatom in said ring, said heterocyclic ring substituents being selected from the group consisting of hydrogen, alkyl (C 1 -C 6 ), halogen, CF 3 , CN and O-alkyl (C 1 -C 6 ), m is an integer from 1-6.  
     
     
         3 . A pharmaceutical composition for treating or preventing pestivirus infection in a mammalian host having or susceptible to said infection, said composition comprising, as active ingredient, a compound as claimed in  claim 1 , in an amount effective to attenuate or arrest infectivity of said virus, and a pharmaceutically acceptable carrier medium.  
     
     
         4 . A pharmaceutical composition as claimed in  claim 3  in the form of a solid comprising said active ingredient and a pharmaceutically acceptable excipient.  
     
     
         5 . A pharmaceutical composition as claimed in  claim 3 , in the form of a liquid comprising said active ingredient and a pharmaceutically acceptable diluent.  
     
     
         6 . A composition as claimed in  claim 3 , in dosage unit form comprising per unit about 0.1 to about 50 mg. of said active ingredient.  
     
     
         7 . A method of treating mammalian cells in culture that are susceptible to infection by, or infected with a pestivirus, said method comprising administering to said cultures an effective amount of a compound according to  claim 1 .  
     
     
         8 . A method for the in vitro treatment of biological material that is susceptible to infection by, or infected or contaminated with a pestivirus, said method comprising treating said material with an effective amount of a compound according to  claim 1.