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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In continuation of research on functionalization of the 2-pyridone core of quinolizidine alkaloids [1, 2], we synthesized 3,5-dibromo-, 3-bromo-, 3-nitro-, 5-nitro-, and 3-amino-derivatives of the quinolizidine alkaloid thermopsine (1).Thermopsine (1) was obtained in S. Yu. Yunusov Institute of the Chemistry of Plant Substances (Tashkent). Its physicochemical constants agreed with those in the literature [3].Bromination of 1 according to the literature [1] produced 3,5-dibromo-derivative 2 in 73% yield. Compound 2 was converted by zinc dust in HCl into 3-bromo-derivative 3 in 90% yield. Nitration of 1 in conc. H 2 SO 4 as before [2] gave 3-nitrothermopsine 4 and 5-nitrothermopsine 5 in a 7:1 ratio in 60% overall yield. Then, compound 4 was reduced by H 2 over Pd catalyst into amine 5 in quantitative yield. The structures of 2-5 were elucidated using PMR and 13 C NMR spectroscopy.Thus, thermopsine (1) derivatives containing functional groups on the 2-pyridone core were synthesized and were promising starting materials for further chemical transformations.The course of reactions was monitored by TLC on ALUGRAM ® plates. Column chromatography (CC) was performed on standard silica gel 60 (0.05-0.1 mm) (Macherey-Nagel, Germany). Melting points of crystalline compounds were determined on a Boetius apparatus. Optical rotation angles were measured on a PerkinElmer 341 LC polarimeter. PMR and 13 C NMR spectra were recorded on equipment at the Khimiya CCU, UfIC, RAS (Bruker Avance III pulsed spectrometer at operating frequency 500.13 MHz for 1 H and 125.47 MHz for 13 C vs. TMS internal standard).3,5-Dibromothermopsine (2). A solution of 1 (0.2 g, 0.8 mmol) in H 2 SO 4 (50%, 5 mL) was treated with KBr (0.29 g, 2.4 mmol) and H 2 O 2 (36%, 0.5 mL, 4.8 mmol), stirred on a magnetic stirrer at room temperature until starting 1 disappeared (TLC monitoring), poured onto ice, neutralized with anhydrous Na 2 CO 3 , and extracted (5 u 10 mL) with EtOAc. The extracts were combined, dried over Na 2 SO 4 , and evaporated. The residue was chromatographed over SiO 2 (C 6 H 6 -MeOH eluent, 9:1) to afford 2 (0.24 g, 73%), dark-yellow amorphous compound, [D] D 20 -40.1q (ñ 1.6, CHCl 3 ).

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