171744-41-5

Arylthiol and dithiobisarylamide antibacterial and antiviral agents have the general formula STR1 where A is monocyclic or bicyclic aryl which can contain up to 3 heteroatoms selected from O, S, and N, R1 and R2 are substituent groups, X is STR2 or SO2 NR4 Z, Y is H or SZ when n is 1, a single bond when n is 2; R4 and Z can be hydrogen or alkyl.

Isothiazolones having the general structure STR1 where A is a monocyclic or bicyclic ring which may contain up to 3 heteroatoms selected from O, S, and N; R1 and R2 are substituent groups such as alkyl, alkoxy, hydroxy, nitro, cyano, amino, and carboxy; and R5 is alkyl, cycloalkyl, phenyl, and Het. The isothiazolones are useful as anti-retroviral agents, anti-inflammatory agents, and anti-atherosclerotic agents.

As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-1 nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-1 activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low μM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.

Antibacterial and antiviral phenylthiols and dithiobisbenzamides have the formula STR1 where n is 1 or 2, Y is hydrogen when n is 1, and a single bond when n is 2; and R1 and R11 are substituent groups, R4 is hydrogen or alkyl, and Z is hydrogen, alkyl, cycloalkyl or sulfamoylphenyl.