Anti-arenaviral compounds

Abstract

Described herein are 4-methyl-piperazine-1-carbothioic acid amide derivatives and analogs, as well as compositions containing the same, for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by hemorrhagic fever viruses, such as Arenaviruses.

What we claim is: 
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound
 selected from the group consisting of:   N1,N4-diphenylpiperazine-1,4-dicarbothioamide;   N-(4-chlorophenyl)-4-methyl-piperazine-1-carbothioamide;   N-(3,4-dichlorophenyl)-4-phenyl-piperazine-1-carbothioamide;   N-(3-chlorophenyl)-4-methyl-piperazine-1-carbothioamide;   N-(2,4-dichlorophenyl)-4-methyl-piperazine-1-carbothioamide;   4-methyl-N-(m-tolyl)piperazine-1-carbothioamide;   N-(3,4-dichlorophenyl)piperidine-1-carbothioamide;   N-(3,4-dichlorophenyl)morpholine-4-carbothioamide;   4-methyl-N-[3-(trifluoromethyl)phenyl]piperazine-1-carbothioamide;   ethyl 4-[(3,4-dichlorophenyl)carbamothioyl]piperazine-1-carboxylate;   N-(3,4-dichlorophenyl)-4-(2-pyridyl)piperazine-1-carbothioamide;   N-(3-methoxyphenyl)-4-methyl-piperazine-1-carbothioamide;   N-(3,5-dimethylphenyl)-4-methyl-piperazine-1-carbothioamide;   N-(2,4-dimethylphenyl)-4-methyl-piperazine-1-carbothioamide;   1-tert-butyl-3-(3,4-dichlorophenyl)thiourea;   N-(4-chloro-2,5-dimethoxy-phenyl)-4-methyl-piperazine-1-carbothioamide;   N-(4-anilinophenyl)-4-methyl-piperazine-1-carbothioamide;   1-(3,4-dichlorophenyl)-3-(4-ethylphenyl)thiourea;   1-(3,4-dichlorophenyl)-3-(m-tolyl)thiourea;   N-(3,4-dichlorophenyl)-4-pyrimidin-2-yl-piperazine-1-carbothioamide;   N-(3-chloro-4-fluoro-phenyl)-4-methylsulfonyl-piperazine-1-carbothioamide;   N-(3-chloro-4-methyl-phenyl)-4-ethyl-piperazine-1-carbothioamide;   1-(3-chloro-4-fluoro-phenyl)-3-[4-(diethylamino)phenyl]thiourea and   1-[(3-chlorophenyl)methyl]-1-(2-morpholinoethyl)-3-phenyl-thiourea.   
     
     
         2 . The pharmaceutical composition of  claim 1 , further comprising an additional antiviral agent selected from the group consisting of zidovudine, acyclovir, ganciclovir, vidarabidine, idoxuridine, trifluridine, foscarnet, interferon, amantadine, rimantadine, and ribavirin. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the compound of Formula I is N-(3,4-dichlorophenyl)piperidine-1-carbothioamide. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the compound of Formula I is N-(3,4-dichlorophenyl)morpholine-4-carbothioamide. 
     
     
         5 . A method for treatment of an Arenavirus infection comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound
 selected from the group consisting of:   N1,N4-diphenylpiperazine-1,4-dicarbothioamide;   N-(4-chlorophenyl)-4-methyl-piperazine-1-carbothioamide;   N-(3,4-dichlorophenyl)-4-phenyl-piperazine-1-carbothioamide;   N-(3-chlorophenyl)-4-methyl-piperazine-1-carbothioamide;   N-(2,4-dichlorophenyl)-4-methyl-piperazine-1-carbothioamide;   4-methyl-N-(m-tolyl)piperazine-1-carbothioamide;   N-(3,4-dichlorophenyl)piperidine-1-carbothioamide;   N-(3,4-dichlorophenyl)morpholine-4-carbothioamide;   4-methyl-N-[3-(trifluoromethyl)phenyl]piperazine-1-carbothioamide;   ethyl 4-[(3,4-dichlorophenyl)carbamothioyl]piperazine-1-carboxylate;   N-(3,4-dichlorophenyl)-4-(2-pyridyl)piperazine-1-carbothioamide;   N-(3-methoxyphenyl)-4-methyl-piperazine-1-carbothioamide;   N-(3,5-dimethylphenyl)-4-methyl-piperazine-1-carbothioamide;   N-(2,4-dimethylphenyl)-4-methyl-piperazine-1-carbothioamide;   1-tert-butyl-3-(3,4-dichlorophenyl)thiourea;   N-(4-chloro-2,5-dimethoxy-phenyl)-4-methyl-piperazine-1-carbothioamide;   N-(4-anilinophenyl)-4-methyl-piperazine-1-carbothioamide;   1-(3,4-dichlorophenyl)-3-(4-ethylphenyl)thiourea;   1-(3,4-dichlorophenyl)-3-(m-tolyl)thiourea;   N-(3,4-dichlorophenyl)-4-pyrimidin-2-yl-piperazine-1-carbothioamide;   N-(3-chloro-4-fluoro-phenyl)-4-methylsulfonyl-piperazine-1-carbothioamide;   N-(3-chloro-4-methyl-phenyl)-4-ethyl-piperazine-1-carbothioamide;   1-(3-chloro-4-fluoro-phenyl)-3-[4-(diethylamino)phenyl]thiourea and   1-[(3-chlorophenyl)methyl]-1-(2-morpholinoethyl)-3-phenyl-thiourea.   
     
     
         6 . The method of  claim 5 , wherein the compound of Formula I is N-(3,4-dichlorophenyl)piperidine-1-carbothioamide. 
     
     
         7 . The method of  claim 5 , wherein the compound of Formula I is N-(3,4-dichlorophenyl)morpholine-4-carbothioamide. 
     
     
         8 . The method of  claim 5 , wherein the mammal is a human. 
     
     
         9 . The method of  claim 5 , wherein an Arenavirus is selected from the group consisting of Junin, Machupo, Tacaribe, Guanarito, Machupo, Pichinde and Lassa. 
     
     
         10 . The method of  claim 5 , further comprising administering to the subject an additional antiviral agent selected from the group consisting of zidovudine, acyclovir, ganciclovir, vidarabidine, idoxuridine, trifluridine, foscarnet, interferon, amantadine, rimantadine, and ribavirin.