COMPOSITION AND STUDY OF NEW MORPHOLINE DERIVATIVES WITH CHOLESTEROL AND LIPID CONCENTRATION REDUCING AND ANTIOXIDANT ACTION

摘要

The present invention relates to the formulation and study of the antioxidant, cholesterol and lipid concentration reducing activity of substituted morpholine derivatives of formula (I)*where R1=CH2CH3; R2=CH3; R3, R4=H, R5=C6H5 or R1=CH2CH2CH2ONO2; R2-CH3; R3, R4=H; R5=C6H5 orR1=H; R2, R3=(CH2)4, R4=H, R5-C6H5 orR1=CH2CH2CH3; R2-R3=(CH2)4, R4=H, R5-C6H5 orR1=CH2CH2CH2ONO2; R2-R3-(CH2)4, R4=H; R5=C6H5 orR1=CH2CH2CH3; R2=CH3; R3-R4=(CH2)4, R5=C6H5 orR1=CH2CH2CH2ONO2; R2=CH3; R3-R4=(CH2)4, R5=C6H5 orR1=CH2CH2CH2ONO2; R2=CH3, R3, R4=H, R5=H orR1=H, R2=p-NO2-C6H4-CH2CH2, R3, R4=H, R5-C6H5.The 2-hydroxy-morpholine derivatives are composed by the reaction of the respective aminoalcohol (22mmol) and 2-bromo-4-phenl acetone (10 mmol) or 2-bromoacetophenone (10 mmol) in ether and acetone for 15 hours at room temperature, whereas the 2-alkoxy-derivatives are composed from the respective 2-hydroxy-derivatives by reaction with the respective alcohol in an acidic environment and heating until they boil. The nitroesters derivatives, where R1=CH2CH2CH2ONO2 are prepared by reaction of the respective 2-hydroxy derivative with 3-bromopropanol-1 as well as the 2-alkoxy derivatives and the conversion of the 2-bromopropoxy derivatives that results in nitroester by boiling with nitrous silver in acetonitrile for 2 hours.The new compounds significantly reduce the content of total cholesterola, total triglycerides and LDL-cholesterol in the plasma.The new compounds have strong antioxidant activity.The new compounds, featuring such properties, could be effectively used for the treatment of high cholesterol and lipid concentration in the blood and for preventing arteriosclerosis.