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A series of 2-methoxyphenyl-9-dialkylaminoethyl derivatives of imidazo[1,2-a]benzimidazole have been synthesized and their pharmacological properties have been studied. Some of the synthesized compounds exhibit antioxidant, radioprotector, antiarrythmic, spasmolytic, antiaggregant, anticalmodulin, and antisecretory properties. Some substances exhibit the properties of phosphodiesterase inhibitors, decrease calcium ion transport through membranes, increase myocardium resistance to hypoxia, and reduce the arterial pressure. The obtained data show good prospects for the synthesis and screening of biologically active substances in this chemical group.Imidazo[1,2-a]benzimidazole contains a guanidine pharmacophore and is a very promising system in the search for new biologically active compounds [1 -8]. In continuation of the previous investigations, we have synthesized a series of new derivatives of 2-phenylimidazo[1,2-a]-benzimidazole containing one or two methoxy groups in various positions of the phenyl ring. The aim of this study was to determine the effect of these substituents on the manifestations of some particular types of biological activity.2-Methoxyphenyl-substituted 9-dialkylaminoethylimidazo[1,2-a]benzimidazoles (VIII -XII) were synthesized using a somewhat modified standard scheme described previously [1,9], proceeding from 1-dialkylaminoethyl-2-aminobenzimidazoles (Ia -Id) and methoxy-substituted phenacylbromides (IIa -IIe).The process of quaternization of the initial amines I was previously carried out in ethanol. However, the high solubility of the target quaternary salts in this medium complicated isolation of the target components and made necessary their conversion into less soluble hydrobromides, which was achieved by adding HBr. In this study, the reactions were performed in aprotic solvents (acetone or acetonitrile), which led to the precipitation of bromides III -VII from the reaction mixtures with good yields. The only exception is the case of 2,5-dimethoxyphenacylbromides VII, which are readily soluble in acetone.Ia -Id; IIa -IId; III -VII; VIII -XII; XIIIa, XIIIb I, III -XII: R = Net 2 (a), N(CH 2 ) 5 (b), N(CH 2 CH 2 ) 2 O (c), NMe 2 (d); IIa, III, VIII: R 1 = 4-OCH 3 , R 2 = H; IIb, IV, IX: R 1 = 3-OCH 3 , R 2 = H; IIc, V, X: R 1 = R 2 = 3,4-(OCH 3 ) 2 ; IId, VI, XI: R 1 = R 2 = 2,4-(OCH 3 ) 2 ; IIe, VII, XII: R 1 = R 2 = 2,5-(OCH 3 ) 2 ; XIII: R = NEt 2 (a), N(CH 2 ) 5 (b).Compounds III -VII crystallize in the form of 2-aminobenzimidazolium salts. This is confirmed by the IR spectra, where two absorption bands due to stretching vibrations of the primary amino groups are observed at 3100 -3350 cm -1 and the characteristic absorption bands of carbonyl groups are found at 1680 -1700 cm -1 (Table 1). 476 0091-150X/05/3909-0476

Three certified preparations of dried extracts of Gymnema sylvestre with gravimetric concentrations of "25%," "50%," and "75%" were studied. After extraction with a water-alcohol mixture, the supernatants of all preparations were analyzed for the presence of phenolic acids and amino acids by ascending thin-layer chromatography. The samples were found to contain significant quantities of a diversity of organic compounds, including plant phenols. The presence of the latter was supported by the reaction with iron (III) chloride and the Pauli diazo reaction. The ninhydrin reaction showed that the samples contained some quantities of amino acids. These were greatest in the 50% preparation (0.15 mol/kg). Gymnema sylvestre was found to contain an interesting amino acid composition, in that there was no proline. According to the certification, the molar concentration of gymnemic acids in properties was 0.12 mol/kg, which was consistent with the concentrations of phenolic acids and amino acids identified in the present studies. Thus, purification of dry extracts of Gymnema sylvestre to obtain pure preparations of gymnemic acids requires procedures to reduce the contents of satellite compounds.

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The Na+/H+ exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N1-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound 6b reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds 3e and 3i inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.