Aliphatic α-hydroxyamino oximes reacted with perfluoroaromatic aldehydes to give α-perfluoroaryl nitrones which underwent cyclization in acetic acid with the formation of 4,5-dialkyl-2-perfluoroaryl-1H-imidazol-1-ols. The latter were also obtained directly from aliphatic α-hydroxyamino oximes and perfluoro­aromatic aldehydes in acetic acid without isolation of intermediate nitrones. The reaction of 4,5-dimethyl-2-perfluoroaryl-1H-imidazol-1-ols with chloroacetone afforded 4,5-dimethyl-2-perfluoroaryl-1H-imidazoles.

Изучена фармакокинетика субстанции нового противооспенного препарата НИОХ-14 (аналога разработанного в США соединения ST-246) у мышей после однократного перорального введения в дозе 50 мкг/г и перорального введения в течение 10 сут в дозах 50 и 5 мкг/г. Концентрацию активного метаболита (то есть ST-246), в который НИОХ-14 превращается в сыворотке крови и гомогенатах органов мышей, определяли методом LC-MS/MS (тандемной масс-спектрометрии — MS/MS и жидкостной хроматографии — LC). На основании фармакокинетических параметров была определена тканевая доступность субстанции НИОХ-14 для разных органов мыши, которая составила 100; 69,6; 20,3; 26,8 и 63,3 % для легких, печени, селезенки, головного мозга и почек, соответственно.

We compared absolute bioavailability of the chemical substance of the anti-smallpox preparation NIOCH-14 and chemical compound ST-246 active against orthopoxviruses after oral administration to mice in doses of 10 and 50 μg/g and intravenous administration to mice in a dose of 2 μg/g body weight. The absolute bioavailability of NIOCH-14 is comparable with the absolute bioavailability of ST-246.

N,N′-Bis(2-hydroxyiminoalkyl)-α,α′-dinitrones are of interest for the synthesis of 1,1′-dihydroxy-2,2′-biimidazoles. Thermal decomposition of two these dinitrones was studied in helium atmosphere. Thermal decomposition of the studied dinitrones at temperature interval 20–500 °C consists of several steps, the first step accompanying with significant exothermic effect (700–1000 J g−1). The first step has been shown to be a two-stage process, and decomposition products have been determined using chromatography–mass spectrometry. Thermogravimetric curves were used for the kinetic studies. Kinetic parameters of decomposition are estimated within the approaches of non-isothermal kinetics (“model-free” kinetics and nonlinear regression methods), with the computer program Netzsch Thermokinetics 2.

A series of novel polycyclic N-amidoimides were synthesized by reacting 4-oxatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione with hydrazides of benzoic acids, arylaminoacetic acid, and oxalic acid. The most pronounced antiviral activities against Vaccinia virus were observed for 4-hydroxy-N-(3,5-dioxo-4-azatetracyclo[5.3.2.02, 6.08, 10]dodec-11-en-4-yl)-3-nitrobenzamide, N-(3,5-dioxo-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-en-4-yl)-N′-[(3-trifluoromethyl)phenyl]ethanediamide, and N-(2,6-dimethylphenyl)-N′-(3,5-dioxo-4-azatetracyclo-5.3.2.02,6,08,10]dodec-11-en-4-yl)ethanediamide.

series of novel polycyclic N -amidoimides were synthesized by reacting 4-oxatetracyclo[5.3.2.0 2,6 .0 8,10 ]dodec-11-ene-3,5-dione with hydrazides of benzoic acids, arylaminoacetic acid, and oxalic acid. The most pronounced antiviral activities against Vaccinia virus were observed for 4-hydroxy- N -(3,5-dioxo-4-azatetracyclo[5.3.2.0 2, 6 .0 8, 10 ]dodec-11-en-4-yl)-3-nitrobenzamide, N -(3,5-dioxo-4-azatetracyclo[5.3.2.0 2,6 .0 8,10 ]dodec-11-en-4-yl)- N′ -[(3-trifluoromethyl)phenyl]ethanediamide, and N -(2,6-dimethylphenyl)- N′ -(3,5-dioxo-4-azatetracyclo-5.3.2.0 2,6 ,0 8,10 ]dodec-11-en-4-yl)ethanediamide.

Синтезированы новые полициклические N-амидоимиды взаимодействием 4-оксатетрацикло[5.3.2.02,6.08,10]додец-11-ен-3,5-диона с гидразидами бензойных кислот, ариламиноуксусной кислоты и щавелевой кислоты. Наиболее выраженную противовирусную активность в отношении вируса осповакцины проявили 4-гидрокси-N-(3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил)-3-нитробензамид, N-(3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил)-N’-[(3-трифторметил)фенил]этандиамид и N-(2,6-диметилфенил)-N’-(3,5-диоксо-4-азатетрацикло-[5.3.2.02,6.08,10]додец-11-ен-4-ил)этандиамид.

Синтезированы новые полициклические N-амидоимиды взаимодействием 4-оксатетрацикло[5.3.2.02,6.08,10]додец-11-ен-3,5-диона с гидразидами бензойных кислот, ариламиноуксусной кислоты и щавелевой кислоты. Наиболее выраженную противовирусную активность в отношении вируса осповакцины проявили 4-гидрокси-N-(3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил)-3-нитробензамид, N-(3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил)-N’-[(3-трифторметил)фенил]этандиамид и N-(2,6-диметилфенил)-N’-(3,5-диоксо-4-азатетрацикло-[5.3.2.02,6.08,10]додец-11-ен-4-ил)этандиамид.

A series of new 1-aryl-3-{3,5-dioxo-4-azatetracyclo[5.3.2.0 2,6 .0 8,10 ]dodec-11-en-4-yl}ureas have been synthesized by reaction of 4-amino-4-azatetracyclo[5.3.2 2,6 .0 8,10 ]dodec-11-en-3,5-dione (II) with aryl isocyanates and phenyl isothiocyanate. The structures of obtained compounds have been confirmed by means of IR and 1 H NMR spectroscopy. Some of these compounds possess pronounced antiviral activity against smallpox vaccine virus. The maximum level of activity was observed for 3-{3,5-dioxo-4-azatetracyclo[5.3.2.0 2,6 .0 8,10 ]dodec-11-en-4-yl}-1-(4-methylphenyl)urea, 3-{3,5-dioxo-4-azatetracyclo -[5.3.2.0 2,6 .0 8,10 ]dodec-11-en-4-yl}-1-(3-fluorophenyl)urea hydrate, and 3-{3,5-dioxo-4-azatetracyclo [5.3.2.0 2,6 .0 8,10 ]dodec-11-en-4-yl}-1-(phenyl)thiourea.

Синтезированы новые производные 1-арил-3-{3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]-додец-11-ен-4-ил}мочевины и изучена их противовирусная активность в отношении вируса осповакцины. Выраженную активность показали 3-{3,5-диоксо-4-азатетрацикло- [5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(4-метилфенил)мочевина, гидрат 3-{3,5-диоксо-4-азатетрацикло-[5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(3-фторфенил)мочевины и 3-{3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(фенил)тиомочевина.

A series of 1-aryl-3-(3,5-dioxo-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-en-4-yl)urea derivatives were synthesized and studied for antiviral activity against smallpox vaccine virus. 3-(3,5-Dioxo-4-azatetracyclo-[5.3.2.02,6.08,10]dodec-11-en-4-yl)-1-(4-methylphenyl)urea, 3-(3,5-dioxo-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-en-4-yl)-1-(3-fluorophenyl)urea hydrate, and 3-(3,5-dioxo-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-en-4-yl)-1-(phenyl)thiourea showed pronounced activity.

Синтезированы новые производные 1-арил-3-{3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]-додец-11-ен-4-ил}мочевины и изучена их противовирусная активность в отношении вируса осповакцины. Выраженную активность показали 3-{3,5-диоксо-4-азатетрацикло- [5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(4-метилфенил)мочевина, гидрат 3-{3,5-диоксо-4-азатетрацикло-[5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(3-фторфенил)мочевины и 3-{3,5-диоксо-4-азатетрацикло[5.3.2.02,6.08,10]додец-11-ен-4-ил}-1-(фенил)тиомочевина.

AIM:Study pharmacodynamic parameters of anti-viral effectiveness of a chemical compound NIOC-14 in experiments in mice infected with ectromelia virus (EV).MATERIALS AND METHODS:EV (K-1 strain) was obtained from the State Collection of Viral Infections and Rickettsioses Causative Agents of the State Scientific Centre of Virology and Biotechnology "Vector". Outbred ICR mice were intranasally infected with EV at a dose of 10 LD50 per animal (10 x 50% lethal doses/animal) and per orally received NIOC-14 or ST-246 as a positive control. Chemical compound NIOC-14 (7-[N'-(4-trifluoromethylbenzoyl)-hidrazincarbonyl]-tricyclo[3.2.2.0(2,4)]non-8-en-6-carbonic acid) was synthesized in Novosibirsk Institute of Organic Chemistry (NIOC). Anti-pox preparation ST-246, developed by SIGA Technologies Inc. (USA), was synthesized in NIOC using the technique described by the authors.RESULTS:50% effective doses against EV in vivo were shown not to differ significantly between the preparations NIOC-14 (3.59 μg/g mouse mass) and ST-246 (5.08 μg/g mouse mass). During determination of therapeutic window, administration of NIOC-14 to mice 1 day or 1 hour before EV infection, as well as 1, 2 and 4 days after EV infection and then for 9 days was found to ensure 100% animal survival. Administration of NIOC-14 as well as ST-246 resulted in the decrease relative to control of EV titers in lungs, nasal cavity, brains, liver, spleen, kidneys and pancreas.CONCLUSION:Anti-viral effectiveness of NIOC-14 against EV in vivo was thus comparable by all the studied pharmacodynamic parameters with anti-viral activity of anti-pox-virus preparation ST-246.

Transformations in the course of high-temperature modification of polyolefins under action of sulfur-containing modifiers have been studied using hexene-1 and hexane as model compounds. Composition of products of thermolysis of bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl] disulfide and bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl] sulfide at 200–270°C has been elucidated by means of thermogravimetry and gas chromatography-mass spectrometry. Mechanism of olefins modification with sulfides and disulfides involving the formation of biradical intermediates is discussed.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A reaction of aliphatic 1,2-hydroxylamino oximes bearing the hydroxylamino group at the secondary carbon atom with aromatic and heteroaromatic aldehydes in acetic acid leads to the corresponding 1-hydroxy-2-aryl(hetaryl)-4,5-dialkylimidazoles in high yields. α-Aryl(hetaryl)-nitrones initially formed by the condensation of 1,2-hydroxylamino oximes with aldehydes are quantitatively converted to the corresponding imidazoles.

In the experiments using intranasal (i/n) infection of mice with the ectromelia virus (EV) in a dose 10 LD50/head (10 x 50% lethal dose/head) or with the monkeypox virus (MPXV) in a dose 10 iD50/head (10 x 50% infective dose/ head) it was demonstrated that the antiviral efficiency of chemical compounds the condensed derivatives of pyrrolidin-2,5-dion, as well as their predecessors and the nearest analogues, synthesized in Novosibirsk institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences (NiOCH SB RAS) was observed. As a positive control we used the antipoxvirus chemical preparation ST-246 available from SiGA Technologies inc. (USA), synthesized in NiOCH SB RAS by the technique suggested by the authors. it was demonstrated that the compound NiOCH-14 (7-[N'-(4-Trifluoromethylbenzoil)-hydrazidecarbonil]-tricyclo[3.2.2.02,4]non-8-en-6-carbonic acid) possessed comparable with ST-246 antiviral activity concerning EV and MPXV on all indicators used. Therefore, at infection of mice with EV (strain K-1) and peroral administration of NiOCH-14 and ST-246 in a dose 50 mkg/g of mouse weight (12-14 g) within 10 days the survival rate and average life expectancy of mice authentically exceeded the control levels. EV titers in lungs through 6 days after infection in the same groups were lower than in the control. in addition to that, after 7 days of infection of mice with MPXV (strain V79-1-005) and daily peroral administration of NiOCH-14 and ST-246 in a dose 60 mkg/g of mouse weight (9-11 g) authentic decrease in a part of infected animals and MPXV titers in lungs was observed.