To evaluate the effect of substituents on biological activities of electron-rich N-containing heterocycles, the variably 2-substituted 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles 26 ± 33 were synthesized and evaluated for antibacterial, antifungal, and enzyme-inhibition activities. The target compounds were obtained from alkyl 4-or 3-hydroxy benzoates 1 and 2, respectively, and from methyl indoleacetate 3. The phenolic OH group of benzoates 1 and 2 were substituted with p-toluenesulfonyl ( 3 4 and 5), benzoyl ( 3 6 and 7), and benzyl groups ( 3 8 and 9) and then converted to 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles. To establish structure-activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO-A inhibiting properties and intermediates 12, 24, 28, and 29 appreciable antifungal activities. Compound 7 inhibits a-chymotrypsin.
Introduction. ± A diversity of biological effects is associated with 1,3,4-oxadiazine and its derivatives, they exhibit cardiovascular [1 ± 3], antibacterial [4], plant-growth regulating [5], miticidal and nematocidal [6], acricidal [7], and insecticidal activities [8]and monoamine-oxidase (MAO) inhibition [9]. The promising therapeutic potential of this class of compounds prompted us to synthesize and biologically screen a series of structural variants of 4H-1,3,4-oxidiazine-5(6H)-ones. To establish structure activity relationships (SAR), the activities of the intervening intermediates were also determined. Thus, the readily available alkyl benzoates 1, 2, and 4 ± 9 and the indoleacetate 3 were transformed to the target 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles 26 ± 33 in excellent yields. The structures of 26 ± 33 were established by spectroscopic techniques, and their biological activities were determined.
