US 9,751,879 B2 · Tricyclic compounds as anticancer agents

Abstract

The present invention is directed to tricyclic compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

A compound of the formula

wherein:
A is
R is independently one or more hydrogen, CD3, halogen, haloalkyl, hydroxyalkyl, CN, CF3, CH2F, CHF2, optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, optionally substituted (C3-C6)cycloalkyl, optionally substituted heterocyclo, —OR4, —CONR3R4, —NR3R4, NR3R4(C1-C6)alkyl-, —NR6OCOR3, —NR6COR3, NR6COR3(C1-C6)alkyl-, —NR6CO2R3, NR6CO2R3(C1-C6)alkyl-, —NR6CONR3R4, —SO2NR3R4, SO2(C1-C6)alkyl-, —NR6SO2NR3R4, —NR6SO2R4 or NR6SO2R4(C1-C6)alkyl-;
X and Y are independently selected from hydrogen, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C8)cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclo;
Z is hydrogen, halogen, —OH, (C1-C6)alkyl, (C1-C6)alkoxy, —NR3R4, —CONR3R4, —OCONR3R4, —NR6OCOR3, —NR6CONR3R4, —NR6SO2NR3R4 or —NR6SO2R4;
R1 is, independently at each occurrence, one or more hydrogen, halogen, —CN, —OR4, —NR3R4, —CONR3R4, —COOH, —OCONR3R4, —NR6OCOR3, —NR6CONR3R4, —NR6SO2NR3R4, —NR6SO2R4, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C 6)alkynyl, optionally substituted (C1-C6)alkoxy, optionally substituted (C3-C8)cycloalkyl, optionally substituted (C3-C8)cycloalkyl (C1-C6)alkyl, optionally substituted (C3-C8)cycloalkyl-CO—, optionally substituted (C3-C8)cycloalkyl-SO2—, optionally substituted aryl (C1-C6)alkoxy, optionally substituted (C3-C8)cycloalkyl (C1-C6)alkoxy, optionally substituted heterocyclyl-CO—, optionally substituted heterocyclyl, optionally substituted (C1-C6)alkyl-SO2—, —NR6SO2— optionally substituted (C1-C6)alkyl, —NR6SO2-optionally substituted heterocyclo, optionally substituted (C1-C6)alkyl-NR 6SO2— or optionally substituted heterocyclo-NR6SO2—;
R2 is hydrogen, halogen, —CN, OH, —CONR3R4, —NR6COOR4, —NR6CONR3R4, —NR6COR4, —NR6SO2R5, —SO2NR3R4, —NR6SO2NR3R4, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C8)cycloalkyl, optionally substituted (C1-C6) alkoxy, optionally substituted aryl, optionally substituted (C1-C6)alkyl-SO2—, optionally substituted aryl-SO2, optionally substituted heteroaryl or optionally substituted heterocyclo;
R3 is hydrogen, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C8)cycloalkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, cyano(C1-C6)alkyl, hydroxy(C1-C6)alkyl, optionally substituted aryl, optionally substituted aryl(C1-C6)alkyl, optionally substituted aryloxy(C1-C6)alkyl, optionally substituted (C1-C6)alkyl-SO2—, optionally substituted heterocyclyl, optionally substituted heterocyclyl(C1-C6)alkyl, optionally substituted heteroaryl or optionally substituted heteroaryl(C1-C6)alkyl,
R4 is hydrogen, optionally substituted (C1-C6)alkyl or optionally substituted (C3-C 8)cycloalkyl;
or R3 and R4 may be taken together with the nitrogen atom to which they are attached to form an optionally substituted (C4-C8) heteroaryl or (C4-C8) heterocyclic ring;
R5 is hydrogen, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C8)cycloalkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, cyano(C1-C6)alkyl, hydroxy(C1-C6)alkyl, optionally substituted aryl, optionally substituted aryl(C1-C6)alkyl, optionally substituted aryloxy(C1-C6)alkyl, optionally substituted (C1-C6)alkyl-SO2—, optionally substituted heterocyclyl, optionally substituted heterocyclyl(C1-C6)alkyl, optionally substituted heteroaryl or optionally substituted heteroaryl(C1-C6)alkyl;
R6 is hydrogen or optionally substituted (C1-C6)alkyl;
R7 is hydrogen, optionally substituted (C1-C6)alkyl, —OR4, CN or halogen;
and/or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

11 more elements

Tricyclic compounds as anticancer agents

Life of this patent

Tricyclic compounds as anticancer agents

Life of this patent

Abstract

Claims13