Registration Number
0221U000136,
0120U100309
, R & D reports
Title
Directed synthesis of novel nitrogen- and oxygencontaining heterocyclic compounds as low molecular weight bioregulators.
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Head
Brovarets Volodymyr S., Доктор хімічних наук
Registration Date
02-01-2021
Organization
V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
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A series of five new 7-(1,4-diazepane)substituted [1,3]oxazole[4,5-d]pyrimidines was synthesized. The antitumor activity of the new compounds at a concentration of 10 μM on 60 cancer cell lines was evaluated. Some of the obtained compounds were selected for five-dose analysis. 7-(1,4-Diazepan)-1-yl-5-(4-methylphenyl)-2-phenyl[1,3]oxazole[4,5-d]pyrimidine and 7-(1,4-diazepane)-1-yl-2-(4-methylphenyl)-5-phenyl[1,3]oxazole[4,5-d]pyrimidine showed the greatest inhibitory effect (GI50 was in the range of 0.9 ÷ 1.9 μm), cytostatic (TGI - 2.1 ÷ 3.6 μM) and cytotoxic (LC50 - 5.9 ÷ 7.4 μM) effects on the studied cancer lines. A convenient method for the synthesis of new sulfonyl analogs of cytosine has been developed: 8-(methyl(phenyl)sulfonyl)-6-R-2,6-dihydroimidazo[1,2-c]pyrimidin-5(3H)-ones and 9-(methyl-(phenyl))sulfonyl)-7-R-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidin-6-ones. It is ocurs by the interaction of 3-(R-amino)-2-(methyl(phenyl)sulfonyl)acrylonitrile with 1-isocyanato-2-chloroethane and 1-isocyanato-3-chloropropane. The obtained heterylsulphones show antiviral activity. It is shown that the reaction of interaction of methyl 2-aryl-5-(chlorosulfonyl)-1,3-oxazole-4-carboxylates with 1H-pyrazole-5-amines and 1H-1,2,4-triazole-5-amines occurs endocyclic nitrogen atoms of aminoazole to obtain products containing the primary amino group. The cyclocondensation pathway has been shown to involve Smiles rearrangement with SO2 extrusion and subsequent elimination of MeOH. This reaction sequence is a convenient approach to the synthesis of new annelated [1,3]oxazole[5,4-d]pyrimidines. A general approach to the synthesis of 2-(dichloromethyl)pyrazolo[1,5-a][1,3,5]triazines and in vitro antitumor activity of them were studied. The study was performed on 60 cancer cell lines for the main types of cancer (leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, breast cancer).
Product Description
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Іvanova Іryna V.
Abdurakhmanova Esma R.
Biletska Іryna M.
Veligina Yevheniia S.
Vydzhak Roman M.
Herasymov Yehor S.
Golovchenko Оleksandr V.
Didiv Nataliya D.
Demydchuk Bogdan A.
Zhirnov Viktor V.
Zyabrev Volodymyr S.
Kachaeva Maryna V.
Kachkovskyi Oleksiy D.
Кlyuchko Svitlana V.
Kozachenko Olexandr P.
Kondratyuk Kostyantyn M.
Mityukhin Оleg P.
Merzhievskiy Danylo O.
Moskvina Viktoria S.
Mrug Galyna P.
Pilyo Stepan G.
Panchyshyn Svitlana Ya.
Polovko Тetiana A.
Porhun Svitlana V.
Prokopenko Volodumir M.
Prostota Yaroslav A.
Rentsevych Тetiana L.
Synenko Vitaliy O.
Slyvchuk Serhiy R.
Solomyanyi Roman M.
Frasinyuk Mykhaylo S.
Charochkina Larysa L.
Chumachenko Svitlana A.
Shablykin Оleg V.
Shablykina Olga V.
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2021-01-02
