Solomiannyi R. Synthesis of bioactive heterocyclic compounds with sulfur and phosphorus-containing groups on the functionalized enamines basis

Due to the interaction of 3-ethoxy-2-methylsulfonylacrylonitrile with N-nucleophiles a number of 4-aminopyrimidines (including heteroannulated by edge a), pyrimidine-2,4(1H,3H)-diones and 4-imino-3,4-dihydropyrimidin-2(1H)-ones with the pharmacophore methylsulfonyl group at position 5 was obtained. By the domino reaction of 3-amino-2-sulfonylacrylonitriles with 2-chloro-1-isocyanatoethane or 3-chloro-1-isocyanatopropane 8-methyl(phenyl)sulfonyl-2,6-dihydroimidazo[1,2-c]pyrimidin-5(3H)-ones and 9-methyl(phenyl)sulfonyl-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidin-6-ones, including acyclonucleosides analogues – compounds with a hydroxyethyl fragment, were synthesized. Functionalized pyrrole (synthesized from 3-amino-2-sulfonyl(phosphoryl/phosphonate)acrylonitrile) have been used for obtaining of 5H-pyrrolo[3,2-d]pyrimidines with PhSO2–, Ph2P(O)–, (EtO)2P(O)– groups in position 7, as well as for the synthesis of 7-phosphonato-1H-1,3,4,5-tetrahydropyrrolo[3,2-d]pyrimidin-2-ones. Heteroaromatic carboxylic acid chlorhydrides have been used to obtain (5-(2-acylhydrazino)-2-(p-tolyl)-1,3-oxazol-4-yl)phosphonates and their products of recyclization under the hydrazine action – (5-hetaryl-1,3,4-oxadiazol-2-yl)(amino)methylphosphonic acids. An approach to the (2-aryl-5-chloro(arylthio)-1,3-thiazol-4-yl)thiophosphonates synthesis based on 1-acylamino-2,2-dichlorovinylphosphonates using the Lawson reagent was developed. Chemical synthesis, IR and NMR spectroscopy (1H, 13C, 31P), LC MS, X-ray, and elemental analysis were used to obtain and prove the structure of these substances. As a result of in vitro biological screening, it was found that 8-sulfonyl-2,6-dihydroimidazo[1,2-c]pyrimidin-5(3H)-one derivatives have the significant activity and selectivity to Human papilloma virus and BK virus, 9-sulfonyl-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidin-6-one – to BK virus; also the activity of pyrrolo[3,2-d]pyrimidine derivatives with sulfonyl and phosphonate group at position 7 was found. It was found that the growth-regulating activity is inherent in many 8-methyl(phenyl)sulfonyl-2,6-dihydroimidazo[1,2-c]pyrimidine-5(3H)-ones and 9-methyl(phenyl)sulfonyl-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidine-6-ones, and in some pyrrolo[3,2-d]pyrimidin derivatives. Scope – bioorganic chemistry.