Substituted amides and hydrazides of mateic acid are known to possess a broad spectrum of biological activity. Maleic amides showed antiinflammatory, hemostatic, and anticoagulant [3] and antiatherosclerotic [4] properties, while some maleic hydrazides exhibited bacteriostatic [5,6], antiinflammatory [5 -8], antihypoxic [9], anticonvulsive [5,6,10], and analgesic effects [5, I l ].Benzylidene-and diarylmethylene hydrazide maleates were reported to have significant antiaggregative and antithrombin activity [ 1,3,11 ]. There are data indicative of the growth retardation and stimulation abilities of substituted maleic hydrazides with respect to plants [12,13].Below we report on the results of investigation of the antiflaviviral activity of some maleic alkyl-and arylamides (I-IV) and maleic phenylacetyl hydrazide (V).Compounds I-V were synthesized by acylation of the corresponding amines and phenylacetic acid hydrazide by maleic anhydride under mild conditions according to the schemeThe proposed structures of compounds I and IV, synthesized for the first time, were established on the basis ofspec-" troscopic data and verified by comparison with the known structures of substituted maleic amides [ 14].
EXPERIMENTAL CHEMICAL PARTThe IH NMR spectra of synthesized compounds were recorded on a RYa-2310 spectrometer (working frequency t State Pharmaceutical Academy, Perm, Russia. 581 60 MHz) using DMSO-d6 as the solvent and HMDS as the internal standard. The IR spectra were measured on an UR-20 spectrophotometer using samples prepared as nujol mulls. Some physicochemical properties of the synthesized compounds are presented in Table 1. The data of elemental analyses agree with the results of calculations according to the empirical formulas.Substituted maleic amides II-IV. To a solution of 0.2 mole of the corresponding amine in 200 ml acetonitrile or ether was added with stirring a solution of 0.2 mole maleic anhydride in 100 ml acetonitrile and the mixture was allowed to stand for 1 -2 h. Then the precipitate was filtered, washed with ether or acetonitrile, and crystallized from ethyl acetate, acetonitrile, or n-butanol.Maleic carbuxymethylamide (I). To a solution of 15.0 g (0.2 mole) glycine in 250 ml water was added with stirring a solution of 19.6 g (0.2 mole) maleic anhydride in 70 ml acetonitrile and the mixture was allowed to stand for 5 h. Then the precipitate was filtered, washed with water, and crystallized from ethyl acetate.Maleic phenylacetylhydrazide (V). To a solution of 16.5 g (0.1 mole) phenylacetic hydrazide in 50 ml glacial acetic acid was added with stirring a solution of 9.8 g (0.1 mole) maleic anhydride in I00 ml ethyl acetate and the mixture was allowed to stand for 1 h. Then the precipitate was filtered, washed with ether, and crystallized from ethyl acetate.IR spectrum (Vm~x, cm-I): 3280 (NHCO), 1730 (COOH), 1680 (C=C), 1646 (CONH).
EXPERIMENTAL BIOLOGICAL PARTExperiments were performed on a group of white mongrel rats weighing 120-160 g. The antiflaviviral effect of compounds I-V was assessed by the...
