Calmangafodipir, a new chemical entity, and other mixed metal complexes, methods of preparation, compositions, and methods of treatment

摘要

Methods for treatment of a pathological condition caused by oxidative stress in a patient comprise administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress. The mixed metals comprise calcium and manganese in a molar ratio of calcium to manganese in the range of 1-10:;
wherein X, R1, R2, R3, and R4 are as defined herein.

主权项

1. A method for treatment of oxidative stress associated with a pathological condition in a patient, the method comprising administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress, wherein the mixed metals comprise calcium and manganese, and wherein the molar ratio of calcium to manganese is 1-10: wherein X represents CH, each R1 independently represents hydrogen or —CH2COOH; each R2 independently represents ZYR6 wherein Z represents a bond, CH2 or CH2O; Y represents a bond or an oxygen atom; R6 is a hydrogen atom, COOR8, alkyl, alkenyl, cycloalkyl, aryl or aralkyl group, optionally substituted by one or more groups selected from COOR8, CONR82, NR82, OR8, ═NR8, ═O, OP(O)(OR8)R7 and OSO3M; R7 is hydroxy, optionally hydroxylated, optionally alkoxylated alkyl or aminoalkyl group; R8 is a hydrogen atom or an optionally hydroxylated, optionally alkoxylated alkyl group; M is a hydrogen atom or one equivalent of a physiologically tolerable cation; provided that each ZYR6 includes a —CH2O— linkage to the respective pyridine ring; R3 represents ethylene; and each R4 independently represents hydrogen or C1-3 alkyl.