Synthesis And Bioacticivies Of Benzimidazolone And Isoxazole Derivatives

Benzimidazolone and isoxazoline derivatives were synthesized and their monoamine oxidase inhibitory activity and antibacterial activity were tested in this thesis.(1) Starting from phenyl selenium bromide reacting with acrylic by selenium electrophilic addition,3-bromo-2-phenyl selenide propionate reagents was prepared. Then by substitution reaction with o-phenylenediamine, followed by ring condensation reaction with triphosgene and nitrogen derivatization, benzimidazolone Phenylselenyl substituted was synthesized. Subsequently by 1,3-dipolar cycloaddition with azide, organic selenium compounds contains 1,2,3-triazole-benzimidazolone biheterocyclic was systhesized. Benzimidazolone contains trans-enamine group and trans-enamine compounds contains 1,2,3-triazole-benzimidazolone biheterocyclic were prepared by selenoxide elimination. This provide a simple synthetic method for synthesis of such trans-enamine.(2) Isoxazoline ester was prepared by 1,3-dipolar cycloaddition of acrylate and substituted aryl oxime; then suffered hydrazino lysis to prepare isoxazoline hydrazide, subsequent acylation to give 5-bishydrazide substituted isoxazoline compounds, finally condensation ring-closure reaction with the amine phosphorus compounds to yield isoxazoline-bis-1,2,4-triazole compounds.(3) Monoamine oxidase inhibitory and antibacterial activity of benzimidazolone and isoxazoline derivatives were tested by fluorescence probe method. The results show that benzimidazolone derivatives 1-6-9, 1-6-11,1-7-1,1-7-4,1-7-7,1-7-8,1-7-9,1-7-13 and 1-10-1 show significant inhibition to MAO-A, while 1-6-7,1-7-1,1-7-7,1-7-12 and 1-7-13 inhibit MAO-B well, among which 1-7-1 and 1-7-13 show excellent inhibition and high selectivity to MAO-A; Most of the isoxazoline compounds inhibit MAO significantly, among which 2-3-3,2-3-4,2-3-8 and 2-3-11 inhibit MAO-A admirably (IC50<0.1μM), whereas 2-3-8 and 2-4-7 are best MAO-B inhibitors (IC50<0.1μM), they exhibit high selectivity to MAO-A except 2-2-5,2-4-7å'Œ 2-7-3.(4) Antibacterial activity of benzimidazolone and isoxazoline derivatives were tested by method of bacteriostatic circle, the results show that benzimidazolone derivatives 1-6-11,1-6-14,1-7-5 and 1-7-10 inhibit Micrococcus luteus well (diameter of antibacterial circle, DAC, over 20mm), among which 1-6-14 acts primely (DAC reach 48mm), while others show no good inhibition to E. coli and Micrococcus luteus. Isoxazoline derivatives are bad Micrococcus luteus & E. coli inhibitors except 2-7-1 and 2-7-2 (DAC over 25mm)...