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alpha-Aminoketone hydrochlorides 2a-d were synthesized by Dakin-West reaction from L-phenylalanine and L-cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a-d with aqueous potassium thiocyanate afforded 1, 3-imidazole-2-thiones 3a-d which were alkylated with methyl iodide to give 2-methylsulfanyl-1H-imidazoles 4a-d with 4-benzyl/4-cyclohexylmethyl and 5-ethyl/5-isopropyl substituents. Coupling of 4a-d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N-1 5a-d and N-3 6a-h alkylated products. The synthesised compounds were tested for their activity against HIV-1. The most active compounds have a cyclohexylmethyl group in the 5-position of 6 and showed an activity against HIV-1 comparable to the activity of Nevirapine.

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Some novel 3,7-dimethyl-6H-pyrazolo [5,1-c][1,2,4]triazin-4-ones were prepared (3a-g). Compounds 3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and 11a,b depending on the type of hydrazine derivative and reaction conditions. The benzoyloxyimino-pyrazolo [5,1-c][1,2,4]triazines (13a,b) were synthesized by refluxing of compounds 3a,b with hydroxylamine hydrochloride to afford the corresponding oxime derivatives followed by treatment with benzoyl chloride.J. Heterocyclic Chem., 38, 711 (2001).For few years, we have been occupied with the chemistry of 1,2,4-triazines[1-3] due to their importance and wide application in biological fields. A number of this class of compounds were found to act as antimicrobial [4], antiviral [5], anti-inflammatory [6][7][8] and antimalarial [9] agents. 4-Amino-1,2,4-triazin-5(4H)-one derivatives have attracted considerable interest, because of their herbicidal activities and important intermediates for the preparation of the fused 1,2,4-triazinone heterocycles [10].In an attempt to synthesize fused 1,2,4-thiadiazine ring with 1,2,4-triazines, we studied the reaction of 4-amino-6-methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine (1) with brominated 1,3-dicarbonyl active methylene compounds. The reaction was carried out by stirring of 1,3-dicarbonyl active methylene compounds (2a-e) with N-bromosuccinimide (NBS) in the presence of benzoyl peroxide in ethanol at room temperature for 1 / 2 hour followed by addition of compound 1 and refluxing for 2 hours. The products from this reaction were shown to be 3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-ones (3a-e) rather than the expected 3,7-dimethyl-6H-[1,2,4]thiadiazino[2,3-c][1,2,4]triazin-4-ones (4a-e) (cf. Scheme 1). In the ir, 1 H nmr and 13 C nmr spectra no observable differences are found capable of differentiating between compounds 3a-e and 4a-e. The only differences capable of differentiating between them were observed in their mass spectra and elemental analyses. Mass spectra showed the existence of the molecular ion peaks M + at m/z 206, 268 and 207 corresponding to 3a, 3b, and 3c respectively and the elemental microanalysis of these compounds for S gave zero %. The proof for formation of elemental sulfur came from its mass spectrum corresponding to M + = 256 (S 8 ). The above results confirm that pyrazolo [5,1-c] The mechanism for the formation of compounds 3a-e is postulated as shown in scheme 2. It proceeds by nucleophilic attack of the amino group of 1 on the carbonyl group of 6a to give 6b, followed by elimination of water from 6b to gave 6c which subsequently undergoes internal nucleophilic attack accompanied by the elimination of hydrogen sulfide to give the 8-bromopyrazolo[5,1-c]-[1,2,4]triazines derivative (6d). Compound 6d undgoes a redox reaction with the eliminated hydrogen sulfide to afford the 8-bromo-6,7,8-trihydropyrazolo[5,1-c]-[1,2,4]triazines (6e) and elemental sulfur. Elimination of hydrogen bromide from 6e afforded the 6,7-dimethyl-6H-