| 主权项 |
1. A method for treating a MLK-mediated disease comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising a compound having the structure of Formula I or a pharmaceutically acceptable isomer, isotope, enantiomer, salt, ester, prodrug, hydrate or solvate thereof, wherein J has a structure ofwhere J is optionally substituted with up to four R10, each R10 is independently selected from the group consisting of halo, alkyl, haloalkyl, alkoxy, haloalkoxy, —OH, and —OCOR6;
X is NR12 or S; each X1, X2, X3, and X4 is independently CH or N and wherein no more than one of X1, X2, X3, and X4 is N; Y is —W—(CH2)n—R1, W is null, phenylene, or —NR6-phenylene, where the NR6 is attached to the imidazopyridazine core structure of Formula I; R1 is —NR2R3, or piperazinyl, where the nitrogen atom of the piperazinyl is optionally substituted with alkyl or alkoxy; R2 is H or alkyl; R3 is selected from the group consisting of C2-C10 alkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, where any atom of R3 is optionally substituted with one or more R7; or R2 and R3 taken together with the N atom to which they are attached form a 3- to 7-membered heterocyclic ring optionally substituted with R8; R4 is H or alkyl; R5 is H, alkyl, or NHR9; R6 is H or alkyl; each R7 is independently alkyl, cycloalkyl, alkoxy, cycloalkoxy, cycloalkylalkyoxy, perhaloalkoxy, halo, oxo, —OH, hydroxyalkyl, —COOR11, or —O—(CH2)m—OH; R8 is alkoxy, hydroxyalkyl, or COOR11; R9 is H, alkyl, or cycloalkyl; R11 is H, or alkyl; R12 is H, or alkyl; n is 0 or 1; m is 1, 2, or 3; and p is 1, 2, or 3; with the proviso that if J is an unsubstituted benzothiophene, then R3 is either aryl or heteroaryl, where any atom of R3 is optionally substituted with one or more R7; and together with at least one pharmaceutically acceptable carrier, diluent or excipient. |
