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Novel derivatives of quinolizidine alkaloid (-)-cytisine were synthesized. Main ADME properties, cytotoxicity against HEK293 cell line and activity against viruses of influenza A/California/7/09(H1N1)pdm09 virus (IAV) and human parainfluenza virus type 3 (HPIV3) were evaluated. It was shown, that 9-carboxamides of methylcytisine (with phenyl and allyl urea's fragments) are most active compounds against IAV probably due to predicted in silico peculiarity of their interactions with the 4R7B active site of IAV neuraminidase. Indexes of selectivity (SI) calculated as ratio of CC 50 /IC 50 of these ureas are 47 and 59 correspondingly (SI of ribavirin is 67, and SI of rimantadin is 5). It was also found, that derivatives obtained from allyl isocyanate and (-)cytisine or 9,11-dibromocytisine are able to inhibit a reproduction of HPIV3 with SI = 58 and 95 (SI of ribavirin is 192 in this case). Moreover, last compound -(1R,5R)- N-allyl-9,11-dibromo-8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-3(4H)-carboxamide with two bromine atom in 2-pyridone core of starting (-)-cytisine molecule, demonstrated high activity against HPIV3 (SI=95) and moderate activity against IAV (SI=16).

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Conjugates of glycyrrhetic acid (GLA) with amino acids (L-isoleucine, -leucine, -valine, and -phenylalanine) were synthesized by the acid-chloride method using methyl or tert-butyl esters of the acids. Tests in MDCK cell culture showed that the GLA conjugate with phenylalanine exhibited high antiviral activity against influenza A/H1N1/pdm09 virus (ED 50 =4.4 Pg/mL, SI = 161).Chemical modification of plant triterpenoids has in the last decade produced a whole series of lead compounds that are medically promising as new antitumor, antiviral, and antidiabetic agents.The pentacyclic triterpenoid glycyrrhetic acid (GLA, 1) is the product from acid and enzymatic hydrolysis of glycyrrhizic acid, the principal constituent of Glycyrrhiza glabra L. and G. uralensis Fisher roots, and is a promising natural product for creating new drugs to treat and prevent oncological and inflammatory diseases, hepatoprotectors, antioxidants, antiulcer and antiviral agents, etc.[1]. The potential to produce new biologically active compounds through chemical modification of GLA has not been fully explored [2][3][4][5].In continuation of our research on the synthesis of new biologically active GLA derivatives, we synthesized aminoacid conjugates using GLA 3-O-acetate (2) as starting material. It was converted into acid chloride 3 via reaction with thionylchloride (SOCl 2 ) in benzene (Scheme 1). The amino acids were methyl or tert-butyl (t-Bu) esters of L-amino acid hydrochlorides and were acylated via reaction with 3 in CH 2 Cl 2 in the presence of Et 3 N or N-methylmorpholine (NMM) to afford conjugates 4-8 in 60-70% yields. The yields of the protected conjugates were higher if the amino-acid t-Bu esters were used as the amines.Analytically pure 4 and 5 were isolated by column chromatography (CC) over silica gel (SG). Conjugates 6-8 were reprecipitated from aqueous EtOH. The protecting groups were removed without further purification.Conjugates 4 and 5 in dioxane:MeOH were treated with aqueous NaOH (4 N) and acidified subsequently with HCl solution (5%) in order to remove the 3-O-acetyl and methyl ester. The t-Bu ester protecting group of 6-8 was removed by trifluoroacetic acid (TFA) in CH 2 Cl 2 at 20-22°C. Then, the 3-O-acetyl protection was removed in dioxane by alkaline hydrolysis using aqueous NaOH (4 N). The resulting compounds were chromatographed over SG to afford free GLA conjugates 9-12 containing free amino acids L-isoleucine (Ile), -leucine (Leu), -valine (Val), and -phenylalanine (Phe) in 53-57% yields.

The reaction between the N‐nitrosohydrazines (I) and ethyl acetoacetate (II) is studied for the first time.

Introduction. Respiratory diseases have always been a serious threat to public health, but in 2020 the situation deteriorated significantly due to the rapid development of the coronavirus infection COVID-19. Due to the lack of available means of ethiotropic therapy and the still insufficient coverage of the general population with vaccination, disinfectants, as well as topical preparations that prevent the penetration of the virus into the body, play an important role in preventing the spread of infection.Aim of the study. This work is devoted to the study of the virucidal activity of the medicine Mestamidin-nos against respiratory viruses, namely influenza A and B viruses, parainfluenza, respiratory syncytial, adenovirus and seasonal coronavirus.Materials and methods. This study was carried out by the suspension method according to MU 3.5.2431-08 “Study and assessment of the virucidal activity of disinfectants”.Results. It was shown that for all studied viruses the use of the compound for 60 minutes led to a complete (up to 0 lgTID50) or sufficient (4 lgTID50) decrease in the viral titer. In the case of a study of a compound with a protein load (imitating strong organic pollution), the effectiveness of the compound was significantly reduced against influenza A viruses, one of the strains of influenza B virus, adenovirus and seasonal coronavirus.Conclusion. Based on the results of the study, it can be concluded that the effective inhibition of pathogens of influenza and acute respiratory infections using the compound MesaMidin®-nos in the absence of strong organic pollution.