| Abstract [eng] |
Derivatives of furo[2,3-d]pyrimidine as oxygen 7-deaza analogue of biogenic purine are of particular interest as research object in organic chemistry and medicine. Various furo[2,3-d]pyrimidines are created or under investigation as potential inhibitors of folic acid cycle enzymes (DHFR, TS), multireceptor tyrosine kinases (EGFR, VEGFR-2, PDGFR-β) or other kinases (Akt, ACK1, Lck). Also furo[2,3-d]pyrimidine derivatives show remarkable antivirus activity against Varicella zoster virus. Study presented in this thesis deals with formation of furo[2,3-d]pyrimidine scaffold and functionalization of this moiety. Some key results of this thesis could be described as follows. Reaction of 2-substituted ethyl-4-aminofuro[2,3-d]pyrimidine-5-carboxylate with ethyl bromopyruvate gave furo[3,2-e]imidazo[1,2-c]pyrimidine-2,9-dicarboxylate derivatives. Study on the reaction of pyrimidin-4(3H)-one with less reactive electrophiles than ethyl bromopyruvate was performed. New method for the synthesis of furo[2,3-d]pyrimidin-4-one has been proposed. The proposed reaction sequence for the synthesis of 5-(arylaminomethyl)furo[2,3-d]pyrimidines expanded the limits of application of the Mitsunobu reaction in the synthesis of secondary amines. It has been shown that reaction of 2-methylthio-5-(phenylaminomethyl)furo[2,3-d]pyrimidin-4-amine with an excess of m-chloroperoxybenzoic acid gave a mixture of furo[2,3-d]pyrimidine-5-carbaldehydes. It has been found, that reaction of methylsulfonyl group of N-((4-amino-2-(methylsulfonyl)furo[2,3-d]pyrimidin-5-yl)methyl)-4-nitro-N-phenylbenzensulfonamide with sodium methoxide in HMPA at room temperature, gives substitution of a 4-nitro group with methoxy instead of 2-methylsulfonyl group. |
