OXATRIAZACHRYSENE DERIVATIVE FOR REDUCING OR RECOVERING MULTI-DRUG RESISTANCE OF CELL, OR CONTROLLING ACTIVITY OF PROTEIN ASSOCIATED WITH MULTI-DRUG RESISTANCE, AND PREPARATION METHOD THEREOF

摘要

PURPOSE: An oxatriazachrysene derivative for reducing or recovering multi-drug resistance of a cell, or for controlling the activity of a protein associated with multi-drug resistance, and a preparation method thereof are provided. The derivative inhibits the activity of P-glycoprotein as a cancer cell having multi-drug resistance, and increases anticancer activity when administered together with an anticancer agent. CONSTITUTION: The oxatriazachrysene derivative for reducing or recovering multi-drug resistance of a cell, or for controlling the activity of a protein associated with multi-drug resistance is represented by the formula(1), wherein R and R1 are independently alkyl, substituted alkyl, cyclo alkyl, substituted cyclo alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl or substituted heterocycle alkyl; R2, R3, R4 and R5 are the same or different, and independently substituted halogen atom, hydrogen, alkoxy, aryloxy, heteroaryloxy or hetero arylalkyloxy; R6 is hydrogen, halogen, nitro, amine, substituted amine, hydroxy, alkoxy, aryloxy, heteroalkyloxy, heteroaryloxy, C1-C20 lower alkyl, substituted alkyl, aryl, substituted aryl, heteroalkyl or heteroaryl; and R7 is hydrogen, CH3, ester(COOR) group, hydroxy methyl or alkoxy methylether. The method for preparing the oxatriazachrysene derivative of the formula(1) comprises reacting a compound of the formula(2) with a compound of the formula(3), or a compound of the formula(4) with a compound of the formula(5) in a solvent and in the presence of base to form an oxazine ring and then form chyrosene structure, wherein R8 is hydrogen or C1-C20 lower alkyl, substituted alkyl, aryl, substituted aryl, C1-C20 heteroaryl, substituted heteroaryl or chiral amino acid; and X is halogen or tosyl.