Kachaeva M. Synthesis and properties of new bioactive 1,3-oxazole derivatives

On the basis of 2-acylamino-3,3-dichloroacrylonitriles new 5-amino-, 5-arylsulfanyl- and 5-arylsulfonyl-1,3-oxazole-4-carbonitriles were synthesized and the structure-activity relationship was established in a number of these compounds. The results of antitumor activity in vitro showed a decisive influence on the bioactivity of the SO2 group at the 5 position of the oxazole ring. On the basis of 1,3-oxazole-5-sulfonyl chlorides a number of new bioactive sulfonylamides containing a cyano- or ester group at the 4 position of the 1,3-oxazole ring were synthesized. The reaction of methyl esters of 2-aryl-5-chlorosulfonyl-1,3-oxazole-4-carboxylic acids with 5-amino-3-R-1H-pyrazoles and 5-amino-3-R-1H-1,2,4-triazoles. Based on the formed sulfonylamides, new tricyclic compounds – [1,3]oxazolo[5,4-d]pyrazolo[1,5-a]pyrimidin-9(4H)-ones and [1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine-9(5H)-ones, and isolated in the individual state intermediates – methyl 5-(1H-pyrazol-5-yl)amino-1,3-oxazole-4-carboxylates. Chemical synthesis, IR and NMR spectroscopy (1H, 13C), chromato-mass spectrometry, X-ray diffraction study, elemental analysis. In vitro biological screening has been carried out for a number of new 1,3-oxazole derivatives. Compounds with significant activity and selectivity for human papillomavirus type-11, cytomegalovirus, and antitumor activity in relation to a wide range of cancer cell lines have been found among them. When comparing the results of antitumor activity of known 1,3-oxazole derivatives, the association of their donor-acceptor properties with the cancer cell inhibition level was revealed. Scope – bioorganic chemistry.