A. F. Goleneva

Synthesis and antiinflammatory activity of derivatives of pyrimido [1,2,4]triazine and of the methylamide of 5-methylamino-1,2,4-triazine-6-carboxylic acid

Among the 3-subst i tuted pyrimido[4, 5-e] [1,2,4]triaz ine-6, 8-diones that we have synthesized, compounds have been detected which possess an ant i inf lammatory activity [1]. Inv iewof this, to elucidate the link between s t ruc ture and ant i inf lammatory activity it appeared desi rable to obtain new derivat ives of this class. At the same time, to asce r ta in the role of the annellated pyridine ring it was of in teres t to study the biological p rope r t ies of 3-subst i tuted der ivat ives of the methylamide of 5 -methy laminol ,2 ,4 t r i az ine -6 -ca rboxy l i c acid, all the more since some compounds of this se r i e s are readi ly obtained by the hydrolyt ic cleavage of the corresponding pyrimido[4,5-e] [1,2,4]triazines [2].

Synthesis and some pharmacological properties of isofervenulin derivatives

Previously, derivatives of isofervenulin were obtained by nucleophilic substitution of a 3-alkylthio group in 5,6,7,8-tetrahydropyrimido[4,5-e]l,2,4-triazine-6,8-diones (Ia-c) by amine residues on extended heating of the reagents [3]. However, the possibilities of this method are limited as a result of the low reactivity of the alkylthio group. Furthermore, as a result of the use of drastic conditions destruction of the pyrimidine ring 6ccurs in certain cases in addition to replacement of the alkylthio group [3].

Synthesis and biological activity of cyanomethoxy-s-triazines

Cyanuric chloride (I) is known to react with simple alcohols in a stepwise manner, so that control of the amount of the alcohol and hydrogen chloride acceptor enables predominantly the 2-alkoxyor the 2,4-dialkoxy-compounds to be obtained. However, when the alcohol used carries an electron-acceptor group in the B-position, the stepwise nature of the reaction is less clearly apparent, with the subsequent formation of difficultly-separable mixtures of alkoxylation products together with unreacted cyanuric chloride [4].

Synthesis and certain properties of 1,3-dimethyl-5-nitrosouracil hydrazine derivatives

Hydrazine derivatives of uracil are used as the starting materials for the synthesis of various compounds of practical importance, including pyrimidotriazine antibiotics [2, i0]. At the same time it has been recently discovered that Fervenulin, the 4-N-oxide antibiotic of the pyrimidotriazine series, when reacted with certain C-nucleophils, can be split into derivatives of 1,3-dimethyl-5-nitroso-6-hydrazinouracil [i]. As a continued examination of this conversion, we synthesized new derivatives of 1,3-dimethyl-5-nitroso-6-hydrazinouracil (IIa-c) bv reacting 5,6,7,8-tetrahydro-6,8-dimethylpyrimido[5,4-e][l,2,4]triazine-5,7dione-4-oxide (Fervenulin-4-oxide, I) with acetylacetone, malonic, and nitroacetic esters. Reaction I with the indicated reagents was carried out as described in [i], in solutions in dry dimethylsulfoxide or dimethylformamide in the presence of triethylamine at room temperature.

Transformations of fervenulin-4-oxide in reactions with several nucleophiles

The t~0SM~o~tion of derivatives of pyrimldo[5,4-e] [l,2,4]-triazin-5,7-dione under the influer~r alcoholic base into 6-azapurine is known [7]. Fervenulin-4-oxide (I) is trans[o~d by heating with 0.5% NaOH into 5,7-dimethylimidazo[4,5-e]as-triazin-6(7H)-one; [3]. Infer~t~on on the reactivity of I with respect to C-nucleophiles is absent from the l~era~ure, :Is ~ is~4~nown, however, that other heterocyclic N-oxides easily react With different C % ~ ~ s in the presence of acylating agents [4].