Furanone Compounds as Kinase Inhibitors

摘要

The present disclosure provides novel furanone compounds, or pharmaceutically acceptable salts, solvates or prodrugs thereof, as Raf kinase, especially BRAF kinase, inhibitors, which are useful therapeutic agents for treatment of Raf kinase related diseases or disorders, such as melanomas, cancers, and leukemia. The disclosure also provides methods and processes for preparing these novel furanone compounds, pharmaceutical compositions containing these furanone compounds, and methods of treatment using these furanone compounds.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
A1 and A2 are independently CH or N;G is N or CX4;R1 is selected from the group consisting of hydrogen, halogen, —NR11R14, —OR12, or —S(O)0-2R13;R11 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, and heteroaryl, each group except hydrogen optionally substituted;R12, R13, and R14 are independently selected from the group consisting of hydrogen, alkyl and cycloalkyl;R2a and R2b are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, and heteroaryl; or alternatively R2a and R2b together with the carbon atom to which they are attached form a cyclic moiety selected from the group consisting of cycloalkyl, cycloalkenyl, and heterocyclyl, each optionally substituted;R3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkyl, alkoxy, and NR31R32;R31 and R32 are independently hydrogen or alkyl; X1 through X4 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, alkyl, alkoxy, and amino;
U is selected from the group consisting of —NH—, —NHC(O)—, —NHS(O)n—, —NHC(O)O—, —NHC(O)NH—, —O—, —C(O)—, —C(O)O—, —OC(O)NH—, —C(O)NH—, —S—, —SO2—, and —S(O)1NH—, wherein each n is independently 1 or 2; andW is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, and heteroaryl, each optionally substituted.