Imidazo[4,5-b]pyridine derivatives as ALK and JAK modulators for the treatment of proliferative disorders

摘要

This application relates to compounds of the Formula I;
as defined herein, and/or salts thereof. This application further relates to compositions and methods of using these compounds and/or salts thereof. The compounds of Formula I are useful as ALK and JAK modulators for the treatment of proliferative disorders.

主权项

1. A compound of the general formula (I): and a salt thereof, wherein: W is H and Z is selected fromor
W and Z are taken together to form R1 is selected from (C6-C10)aryl, aminophenyl, (C2-C9)heterocycloalkyl, (C1-C9)heteroaryl and a group of formula wherein any of the foregoing may be optionally substituted with one or more R6 groups; R2 is selected from hydrogen and halogen; R3 is selected from CH2OH and CONR4R5; Q is selected from CH2 and O; “------” is either present so as to form a double bond or is absent; R4 and R5 are each independently selected from H, (C1-C6)alkyl, (C3-C8)cycloalkyl, (C1-C6)alkyl(C3-C8)cycloalkyl, and (C1-C6)alkyl-OR9 wherein any of the foregoing except for H may be optionally substituted with one or more R7; each R6 is independently selected from (C0-C4)alkylCO2R8, (C0-C4)alkylCON(R8)2, (C0-C4)alkylCOR8, (C0-C4)alkylN(R8)2, (C0-C4)OR9, (C1-C6)alkoxy, (C1-C6)alkoxy(C2-C9)heterocycloalkyl, (C1-C6)alkoxy(C3-C8)cycloalkyl, (C1-C6)alkyl, (C1-C6)alkyl(C1-C9)heteroaryl, (C1-C6)alkyl(C2-C9)heterocycloalkyl, (C1-C6)alkyl(C3-C8)cycloalkyl, (C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl, (C2-C6)alkenyl, (C2-C9)heterocycloalkyl, (C2-C9)heterocycloalkyloxy, (C3-C8)cycloalkyl, (C3-C8)cycloalkyloxy, (C3-C9)heterocycloalkenyl, (C6-C10)aryl, cyano, halo(C1-C6)alkoxy, halo(C1-C6)alkyl, halogen, O(C0-C4)alkylCO2R8, O(C0-C4)alkylCON(R8)2, O(C0-C4)alkylCOR8, PO((C1-C4)alkyl)2, and O(C0-C4)alkylN(R8)2, wherein any of the foregoing except for halogen, may be optionally substituted with one or more R7; each R7 is independently selected from (C0-C4)alkylCO2R8, (C0-C4)alkylCON(R8)2, (C0-C4)alkylCOR8, (C0-C4)OR9, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkyl(C1-C9)heteroaryl, (C1-C6)alkyl(C2-C9)heterocycloalkyl, (C1-C6)alkyl(C3-C8)cycloalkyl, (C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl, (C2-C9)heterocycloalkyl, (C2-C9)heterocycloalkyl optionally substituted with (C1-C6)alkyl, (C3-C8)cycloalkyl, (C6-C10)aryl, halo(C1-C6)alkoxy, halo(C1-C6)alkyl, halogen, hydroxy(C1-C6)alkyl, PO((C1-C4)alkyl)2, and hydroxy(C1-C6)alkyl(C1-C6)alkoxy; each R8 is independently selected from H, (C1-C6)alkyl, and (C2-C9)heterocycloalkyl, or two R8 are taken together with the nitrogen atom to which they are attached to form (C2-C9)heterocycloalkyl, wherein any of the foregoing except for H, may be optionally substituted with (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, halogen, (C0-C4)alkylCO2R9, (C0-C4)alkylN(R9)2 or (C0-C4)alkylOR9; R9 is independently selected from H and (C1-C6)alkyl; and R10 is independently a carbonyl or a hydroxyl group.