1-(3-(2-AMINO-4-PYRIMIDINYL)- 4-HYDROXYPHENYL)-3,4-PYRROLIDINEDIOL DERIVATIVES AS INHIBITORS OF CYCLIN DEPENDENT KINASE WHICH IS USEFUL FOR PREVENTION AND TREATMENT OF CANCER

摘要

PURPOSE: 1-(3-(2-Amino-4-pyrimidinyl)- 4-hydroxyphenyl)-3,4-pyrrolidinediol derivatives as inhibitors of cyclin dependent kinase are provided, which compounds effectively inhibit cyclin dependent kinase, so that they can be useful for prevention and treatment of cancer. CONSTITUTION: The 1-(3-(2-Amino-4-pyrimidinyl)- 4-hydroxyphenyl)-3,4-pyrrolidinediol derivatives represented by formula (1), and pharmaceutically acceptable salts, hydrates, solvates and isomers thereof are provided, wherein R is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkyl of which ring contains nitrogen or oxygen, optionally substituted cycloalkyl of which ring contains nitrogen or oxygen, optionally substituted alkyl using nitrogen or oxygen as a linker, optionally substituted alkyl of which ring contains nitrogen or oxygen using nitrogen or oxygen as a linker, optionally substituted cycloalkyl of which ring contains nitrogen or oxygen using nitrogen or oxygen as a linker, or hydroxy. A method for preparing the compounds of formula (1) comprises the steps of: reacting a compound of formula (2) with R-carboxylic acid to prepare a compound of formula (3); aldol condensation of the compound of formula (3) to prepare a compound of formula (4); reacting the compound of formula (4) with guanidine to prepare a compound of formula (5); amination of the compound of formula (5) to prepare a compound of formula (7); reacting the compound of formula (7) with 5,6-bis(iodized methyl)-2,4,7,9-tetraoxadecane to prepare a compound of formula (8); and hydrolysis of the compound of formula (8).