Synthesis and in vitro anticancer and anti-HIV evaluation of new 2-mercaptobenzenesulfonamides.

The reactions of 6-chloro-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide derivatives with appropriate diamines were investigated. Depending on the reaction conditions 2-mercaptobenzenesulfonamide derivatives or their oxidation product disulfides were obtained. All the compounds were tested at the US National Cancer Institute (Bethesda) for their in vitro anticancer and anti-HIV activities. The highest sensibility against leukemia cell lines was found for bis[2-(6-chloro-4-phenyl-3,4-dihydroquinazolin-2-yl)aminosulfonyl-5-chloro-4-(4-R2-phenylcarbamoyl)phenyl]disulfides (R2 = H or Cl). The results of anti-HIV tests displayed moderate activity of N-(pirydo[3,2-d]imidazol-2-yl)-2-mercaptobenzenesulfonamide.

Synthesis of 1-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives with potential pharmacological activity.

Syntheses of 1-amino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [Va-o], 1-benzylidencimino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [X, XII-XIX] and N-(4-chlorobenzylidene)-N'-(6-chloro-7-methyl-l, 1-dioxo- 1,4,2-benzodithiazin-3-yl)hydrazine [XX] have been described. The moderate anticancer and weak anti-HIV activities were observed in vitro for compounds [Va, e.g]. The obtained compounds were evaluated for their in vitro antimycobacterial activity towards a strain of Mycobacterium tuberculosis H 37 Rv.

Syntheses of S,N-substituted 2-mercaptobenzenesulfonamide derivatives with potential pharmacological activity.

A series of [5-chloro-4-methyl-2-sulfamoylphenyl(thio or sulfonyl)]alkanoic acids [I-VI], their methyl esters [VII-XII] and hydrazides [XIII-XXI] were prepared. The treatment of the selected esters [VII-VIII, XI-XII] with appropriate biguanide hydrochlorides gave 4-chloro-5-methyl-2-[2-amino-6-R3-triazin-4-ylalkyl(thio or sulfonyl)]benzenesulfonamides [XXII-XXVII]. The anticancer activity was observed in vitro for compound [XXII].

Synthesis, anti-HIV and anticancer activities of new 4-(2-mercaptobenzenesulfonyl)perhydro-1,2,4-triazin-3-ones.

Syntheses of N-(6-chloro-1,1-dioxo-7-R1-1,4,2-benzodithiazyn-3-yl)-N'-(2- hydroxyethyl)hydrazines (IIa-d], N-(6-chloro-1,1-dioxo-7-methyl-1,4,2-benzodithiazyn-3-yl)-N'-(2- chloroethyl)hydrazine [IV], 4-(4-chloro-5-R1-2-mercaptobenzenesulfonyl)perhydro-1,2,4-triaz in-3-ones [IIIa-d] and 5-chloro-4-methyl-2-(3-oxoperhydro-1,2,4-triazin-4- ylsulfonyl)phenylthioacetic acid [V] have been described. Preliminary screening data have indicated that compounds [IIIa-d] exhibit either a moderate or a high anti-HIV activity and a moderate anticancer activity in some human tumor cell lines.

2-Mercapto-N-(azolyl)benzenesulphonamides. IV. Syntheses of some 4-chloro-2-mercapto-5-methyl-N-(benzimidazol-2-yl)benzenesulph onamide derivatives with potential anticancer and anti-HIV activities.

Syntheses of 4-chloro-2-mercapto-5-methyl-N-(5-R1-6-R2-benzimidazol-2-yl) benzenesulphonamides [II-V], their disulfides [IIa-IVa] and S,N-substituted derivatives [VI-IX] were described. The probable mechanism for the reactions was suggested. The moderate anticancer activity was observed in vitro for compounds [II-IV].

Derivatives of 2-mercaptobenzenesulphonamide. XX. Synthesis and cardiovascular effects of some 2-[4-chloro-2-(2-dialkylaminoethylthio)-5-methylbenzenesulphonylimino]- perhydropyrimidines.

A series of 2-[4-chloro-2-(2-dialkylaminoethylthio)-5-methyl- benzenesulphonylimino]perhydropyrimidines [IV-X] and their hydrochlorides [IVa-VIIIa] were prepared. The antiarrhythmic effect of the most active compound [Va] was comparable to the reference drugs, quinidine and procainamide. The influence of the tested compounds [IVa, Va, VIa] on the blood pressure and heart rate of rats as well as the acute toxicity in mice were studied.

Derivatives of 2-mercaptobenzenesulphonamide. XXI. Syntheses and cardiovascular effects of N-(dimethylaminoethyl)amides of 2-(perhydropyrimidin-2-yliminosulphonyl)-phenylthioalkanoic acids.

A series of 2-[5-chloro-4-methyl-2-(perhydropyrimidin-2-yl iminosulphonyl)phenylthio]alkanoic acids [IV-XI], their methyl esters [XII-XIX], N-(2-dimethylaminoethyl) amides, [XX-XXV] and the corresponding hydrochlorides [XXa-XXIVa] were obtained. The hydrochlorides [XXa, XXIIa, XXIVa] exhibited a comparable or stronger antiarrhythmic activity than the reference drugs, quinidine and procainamide. The influence of the tested compounds on the blood pressure and heart rate of rats as well as the acute toxicity in mice were studied. Some structure-activity relationship were also discussed.

Derivatives of 2-mercaptobenzenesulphonamide. XIX. Syntheses, anticancer and anti-HIV activities of some 2-(4-chloro-2-mercaptobenzenesulphonylimino) perhydropyrimidines.

Syntheses of some 2-(4-chloro-2-mercaptobenzenesulphonylimino)perhydropyrimidine+ ++ derivatives are described. The moderate anticancer and weak anti-HIV activities were observed in vitro for compounds [IX-XI].

Derivatives of 2-mercaptobenzenesulphonamide. XVIII. Syntheses and cardiovascular effects of some S- and S,N-substituted 4-chloro-2-mercapto-5-methyl-N-(5-amino-1,2,4-triazol-3-yl) benzenesulphonamide derivatives.

The syntheses of salts [III, IV] and amides [V, V.HCl] of 2-[5-chloro-4-methyl-2-[(5-amino-s-triazol-3-yl)aminosulphonyl+ ++] phenylthio] alkanoic acids, as well as 5-amino-2-[2-(2,4-dimethylpiperidino) ethyl]-3-[4-chloro-2-[2-(2,6-dimethylpiperidino) ethylthio]-5-methylbenzenesulphonylimino]-1-methyl-delta 4-1,2,4-triazoline dihydrochloride [X] and 5-(amino-, 4-chloroanilino- or 3,4,5-trimethoxyanilino)-1,2-di[2-(2,6-dimethylpiperidino) ethyl]-3-(4-chloro-2-[2-(2,6-dimethylpiperidino) ethylthio]-5-methylbenzenesulphonylimino)-delta 4-1,2,4-triazoline trihydrochlorides [XI-XIII] are described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of compounds III, IV, V.HCl and X-XIII are presented. The antiarrhythmic effect of the most active [XI] was stronger or comparable to the reference drugs quinidine and procainamide.

Derivatives of 2-mercaptobenzenesulphonamide. XVII. Synthesis and some pharmacological properties of 1-[4-R-5-cyano-2-dialkylaminoalkylthio)benzenesulphonyl]-2-imidiazolidi none hydrochlorides.

Syntheses of 1-[4-R-5-cyano-2-(dialkylaminoalkylthio)-benzenesulphonyl]- 2-imidiazolidinones [IIIa-h,IVa-m] and their hydrochlorides [Va-h, VIa-m] are described herein. The results of preliminary pharmacological examinations, such as acute toxicity and influence on the circulatory system are presented. Some structure-activity relationship are also discussed.

Derivatives of 2-mercaptyobenzenesulphonamide. XIII. Syntheses and somepharmacological properties of 1-4-chloro-2-(dialkylaminoalkylthio)-5- methylbenzenesulphonyl)-2-imidazolidinone hydrochlorides.

Syntheses of 1-[4-chloro-2-(dialkylaminoalkylthio)-5- methylbenzenesulphonyl]-2-imidazolidones [II-X] and their hydrochlorides [IIa-Xa] are described. The results of preliminary pharmacological examination such as acute toxicity and influence on circulatory system are presented.