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Seven 2,5-diarylalkyloxysubstituted 1,3,4-oxadiazoles were synthesized. They showed pronounced antiphlogistic action together with central activity (sedative, analgesic) that principally seems to be connected with the presence in the molecule of the 3,4-dioxymethylenephenyl radical.

Following previous research which showed the antibacterial and antimycotic activity of triazolin-3-thiones (II), a series of compounds has been prepared and tested to correlate and clarify the structure-activity relationships. The compounds were of the type represented in (II) where (R = H, CH3 or C6H5) and were in detail: 3-methylthiotriazoles (III-VIII), 3-(amino-substituted)ethylthiotriazolines (IX-XXVI), 3-carboxymethylthiotriazolines (XXVII-XXX), 3,3'dithiobistriazolines (XXXI-XXXVI) and 2-amino-methyl-N-substituted triazolin-3-thiones (XLVIII-LXVI). The 2-aminooxadiazoles (XXXVII-XLII), obtained in place of the expected 1-aroyl-S-methylisothiosemicarbazides (II a) from the reaction between thiosemicarbazides (I) (R = H; CH3, C6H5) and methyl iodide, are also described.

In continuation of previous work, the Authors describe the synthesis of 3-aminoethyl derivatives of some 5-aryl-1,3,4-oxadiazol-2-ones whose structure has been confirmed by I.R., N.M.R. and mass spectral methods. The results of pharmacological testing are also reported and these further clarify some aspects of the biological activity of the oxadiazole structure.

In continuation of previous work designed to obtain derivatives of 2-mercapto-1,3,4-oxadiazole of possible biological interest, the Mannich bases (III - XXX) were prepared. The compounds prepared bear at position 5, with respect to the oxadiazole nucleus, 3,4,5-trimethoxy and 3,4-dihydroxymethylenephenyl radicals which have proved of interest in other series of derivatives. The antimycotic activity of the compounds is reported.

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.

The behaviour of alkaline salts of some aroyl-hydrazine-carbodithioic acids [comp. Ia,b,c,] and derivatives of 1,3,4-oxadiazole [comp. IIa,b,c, e IIIa,b,c] , has been studied, on the capability of lymphoblasts in vitro, in consequence of stimulation by some mitogen agents (PHA, PWM). It has been pointed out that the considered compounds inhibit the cellular mitosis in variable percentage in relation to their structure and to the used mitogen agent, frequently causing some mitogen-like morphological modification, also revealable under a optical microscope. The higher inhibition has been obtained by the Ic, IIc, and IIIc compounds, in which Ar is the 3,4-dihydroxymethylenephenyl radical, proving selective, in some cases, for the T lymphocytes.

The preparation of a series of aroylhydrazones of halogenobenzaldehydes (I) - (XI) is described together with that of the corresponding reduction products (XII) - (XXV) and of 2,5-diaryl-1,3,4-oxadiazoles with halogen substitution (XXVI) - (XLIII). The results of pharmacological and microbiological examination of the compounds is reported.

The synthesis of imidazo [2,1-b]-1,3,4-thiadiazole derivatives and preliminary pharmacological screening are reported. The compounds studied showed mainly antiphlogistic, antipyretic and analgesic activity. From the results it appears that analgesic activity is peripheral.

A series of 1-aroyl-4H(R)-thiosemicarbazides (IV-XVIII) and the corresponding 5-phenyl-4H(R)-1,2,4-triazolin-3-thiones (XIX-XXXIII) were synthesized: biological assay demonstrated their in vitro antibacterial and antimycotic activities. The preparation of same hydrazinoaroylthiazoles (XXXIV-XXXVI) was reported also, obtained by condensation of 1-aroyl-4H-thiosemicarbazides with phenacyl bromide and the synthesis of thiazole[3,2-b]-s-triazol-3(2H)-ones (XLIX-LI) prepared by cyclodehydration of carboxymethylthiotriazoles (XLVI-XLVIII). The results of pharmacological testing for both series of derivatives (XLIX-LI) and (XLVI-XLVIII) showed good antiinflammatory and antipyretic activities.

Work was continued on the pharmacological study of the 1,3,4-oxadiazole nucleus using aroylhydrazines already used for the synthesis of anti-MAO compounds. S-alkylaminoalkyl derivatives of some 2-mercapto-5-aryl-1,3,4-oxadiazoles were prepared bearing in the 5-position a 3,4,5-trimethoxyphenyl, a 3,5-dimethoxy-4-ethoxyphenyl or a 3,4-dihydroxymethylenephenyl radical. When subjected to pharmacological investigation the compounds showed clear hypotensive activity partially antagonized by atropine and antispastic activity on smooth muscle.

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.

Two new series of 2-aryletenylthiazolo-4-acetic (IV-XII) and 4-carboxylic (XIII-XXI) acids substituted with alkoxy groups in the benzene ring were synthesized. The compounds were subjected to comparative tests of antiinflammatory, analgesic and antipyretic activity.