Potential of pyrazolooxadiazinone derivatives as serine protease inhibitors.

As a part of an investigation on molecular hybrids as new serine protease inhibitors, the pyrazolo [4,3-c][1,2,5]oxadiazin-3(5H)-one ring system was selected as a model of potential mechanism-based inhibitors. Due to the inherent reactivity of this system an optimal balance between susceptibility to nucleophilic attack and stability in solvents was sought prior to development as therapeutic agents. Substitutions on N5 and C7 of the supporting pyrazole ring with either aliphatic or aromatic groups (compounds 2 a-m) and the replacement of the carbonyl oxygen on the reactive oxadiazinone ring with sulfur (compounds 3a,i) were explored.

6-Alkyl and 6-arylcarbamoyloximino pyrazolo[3,4-b][1,4]diazepines as potential fungicidal, insecticidal and herbicidal agents.

A series of 6-alkyl and 6-arylcarbamoyloximinopyrazolo[3,4-b][1,4]diazepines was prepared and evaluated for fungicidal, insecticidal and herbicidal activity. No one compound showed a general effect but individual compounds exhibited specific activities.

Pyrazolo[3,4-d][1,2,3]triazole-1-carboxamides and 5-alkylaminopyrazolo[3,4-d]oxazoles: synthesis and evaluation of the in vitro antifungal activity.

A series of N-alkyl-N'-(4-diazo-5-pyrazolyl)-ureas (4) was thermally and photochemically converted into pyrazolo [3,4-d][1,2,3]triazole derivatives (5,6) and 5-alkylaminopyrazolo[3,4-d]oxazoles (7) respectively. The products were tested for in vitro antifungal activity against Fusarium culmorum, Botrytis cinerea, Phoma betae, Pythium ultimum, Sclerotinia minor and Rhizoctonia solani. The MIC and ED50 values of compound (6) against some of the test fungi were comparable to those of the reference fungicides iprodione and mancozeb.

4-Diazo-5-alkylsulphonamidopyrazoles: synthesis and evaluation of biological activity.

A series of 4-diazo-5-alkylsulphonamidopyrazoles (5) was prepared and tested for antitumor, antiviral and antimicrobial activity. Compounds (5a) and (5b) showed a selective, although not very potent cytostatic activity against L1210 and a human T lymphoblastoid cell line (C8166). Compounds (5a) and (5d-h) showed a selective anti-coxsackie B1 virus activity, whereas 5b was also endowed with some activity against Bacillus subtilis.

Synthesis and antifungal activity of 4-thiazol-2-yl-5-aminopyrazoles and 4-aminopyrazolo [3,4-c] isothiazoles.

Starting from 4-thiocarbamoyl-5-aminopyrazoles (I), the AA could prepare two series of products: 4-thiazol-2-yl-5-aminopyrazoles (II) and 4-aminopyrazolo [3,4-c] isothiazoles (III). The screening for in vitro antifungal activity evidenced that compounds (III) are effective in controlling most examined fungi; in particular 1-phenyl-3-methyl-4-aminopyrazolo [3,4-c] isothiazole (III a) at the concentration of 20 p.p.