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In continuation of previous research designed to obtain compounds of pharmacological interest, the following substances were prepared, from the potassium salts (I-III) and from the methyl esters (IV-VI) of some aroylhydrazinocarbodithioic acids, derivatives of 1,3,4-oxadiazole (VII-XV), of 3-aminorhodanine (XVI-XVIII), of 1,2,4-triazole (XIX-XXI), of 7H-(1,2,4)-triazol[3,4-b] [1,3,4] thiadiazine (XXII-XXIV) and of 1,3,4-thiadiazole (XXV-XXX). The compounds have present in the molecule a nucleus and radical which have produced marked biological activity in other series of compounds. To date some of the above compounds have shown antibacterial, antimycotic and antimitotic activity.

A series of 4-propylderivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c] [1,2,4]benzothiadizine-5,5-dioxide substituted or unsubstituted in the benzene ring was synthesized. Derivatives of these compounds together with those of the corresponding 4-methyl and 4-ethyl derivatives prepared previously were tested for cardiovascular effects in the anesthesized rat. All the compounds studied showed hypotensive activity which was particularly intense for compounds (X), (XIX), (XXII), (XXV), and produced an increase in differential pressure marked for (XXV) and (XXVIII) which was often accompanied by pronounced bradycardia (XVII), (XVIII) and (XIX). The results prove that derivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo-[2,1-c][1,2,4]benzothiadiazine-5,5-dioxide have hypotensive and bradycardizing activity. Structure-activity relationships are discussed.

Series of alkyl derivatives of the following have been prepared: 5,7-dichloro- [compounds (II leads to V)], 6-methyl- [compounds (VI leads to IX)] and 6-methoxy-3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide [compounds (X leads to XIII)]. The products were tested for antimicrobial activity. Studies were also made of the corresponding 3-mercapto precursors (XIV, XV, XVI) and the relative 3-picolinium salts (XVII, XVIII, XIX) and also of the 3-picolinium salts of 6-chloro-, 7-chloro- and 6,7-dichloro-3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide (XX, XXI, XXII). Some of the 3-alkylmercapto compounds, and especially the 5,7-dichloro derivative, inhibited various strains of Gram-positive bacteria of the genus Staphylococcus, while the same substances proved much less effective against the genera Streptococcus and Diplococcus. Antimicrobial activity appeared to be influenced by the length of the alkyl chain as well as by the nature and position of the substituents on the benzene ring. The compounds proved inactive against the Gram-negative schizomycetes (Salmonella, Shigella, Escherichia, Proteus, Pseudomonas. Enterobacter, Klebsiella, Serratia, Yersinia, Providencia) and against yeasts (Candida) with the exception of compound (V) which showed slight bacteriostatic action against three strains of Candida albicans.

A series of 4-dimethylaminoethyl and 4-diethylaminoethyl derivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c] [1,2,4] benzothiadiazine-5,5-dioxide substituted or unsubstituted in the benzene ring was prepared and subjected to preliminary investigation using the cardiovascular system of the anesthesized rat. Introduction of a basic group in the alkyl chain on N4 gives compounds with good hypotensive activity, this being most pronounced for (III, IV a and XIV) and an increase in differential pressure, marked for (V a, X, XII). These effects are sometimes accompanied by some bradycardizing activity, most marked for (V a) and (X). The results therefore confirm that derivatives of tetrahydropyrrolbenzothiazine have cardiovascular activity. Structure-activity relationships are discussed.

Starting from 3-aryl-4-amino-5-mercapto-4H-1,2,4-triazoles (II), two series of 3,6-disubstituted 7H-1,2,4-triazol [3,4-b] [1,3,4] thiadiazines (III) and their 5-carboxymethylthio derivatives (IV) were prepared. From the mercapto-amino-triazoles (II) because of their reactivity in some oxidising media, were obtained the triazole derivatives (V), (VI) and (VII). The synthesis of the alpha-thioketones (VIII) of 3-aryl-5-mercapto-1,3,4-oxadiazoles (I), used in alternative synthesis of triazole-thiadiazines (III), is also reported. All the substances described were subjected to biological screening. In the tests, the carboxymethylthiotriazole (IV) showed weak antiinflammatory activity (carrageenin edema) and more consistent scavanger activity, in vitro, on superoxide anions. The triazole-thiadiazines (III) and triazoles (II), (V) and (VI) showed moderate antimycotic activity.