CHROMAN-2-CARBOXYLIC ACID ARYLAMIDE DERIVATIVES, METHOD OF THE SAME AND NF-KAPPAB INHIBITOR COMPRISING THEREBY

摘要

A novel chroman-2-carboxylic acid amide derivative compound and a pharmaceutical composition comprising the same are provided to act as an inhibitor of NF-kappaB, thereby capable of preventing or treating diseases related to the NF-kappaB such as multiple myeloma, rheumatoid arthritis, and cancer. A chroman-2-carboxylic acid amide derivative is represented by the formula(1-a) or (1-b). In the formula(1-a), each R1, R2, R3, R4 and R5 is same or different and is independently H, hydroxy, C1-4 alkoxy, C1-4 alkyl, trifluoromethyl, halogen, or nitro. In the formula(1-b), each R1, R2, R3, R4 and R5 is same or different and is independently H, hydroxy, C1-4 alkoxy, C1-4 alkyl, trifluoromethyl, halogen, or nitro, provided that all R1 to R5 being H, or R1 and R3 to R5 being H and R2 being nitro, or R1 to R3 and R5 being H and R4 being nitro are excluded. A method for preparing the chroman-2-carboxylic acid amide derivative of the formula(1-a) comprises the steps of: (a) treating 2-hydroxyacetone phenone and oxalic acid diester under a base and then treating them with an acid to prepare a compound represented by the formula(2-a); (b) subjecting the compound of the formula(2-a) to a catalytic reduction under an ethanol-acetic acid solvent and a Pd/C catalyst to prepare a compound represented by the formula(3-a); (c) treating the compound of the formula(3-a) with potassium hydroxide to prepare a compound represented by the formula(4-a); and (d) treating the compound of the formula(4-a) with an amine compound to prepare the compound of the formula(1-a). A pharmaceutical composition for preventing or treating multiple myeloma, rheumatoid arthritis, or cancer comprises the chroman-2-carboxylic acid amide derivative or a pharmaceutically acceptable salt thereof as an effective ingredient and a pharmaceutically acceptable carrier.