The compound, methods of inhibiting the activity of the RAF in a cell, and cell proliferation, in vitro or in vivo, use of a compound, and methods of treating a disease or condition that is enhanced by inhibition of RAF, and treating a proliferative condition.

摘要

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B-RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formula (I): wherein: J is independently -O- or -NRN1-; RN1, if present, is independently -H or a substituent; RN2 is independently -H or a substituent; Y is independently -CH- or -N-; Q is independently -(CH2)j-M-(CH2)k- wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently -O-, -S-, -NH-, -NMe-, or -CH2-; each of RP1, RP2, RP3, and RP4 is independently -H or a substituent; and additionally RP1 and RP2 taken together may be -CH-CH-CH-CH-; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently -CH2-, -NRN-, -C(-X)-, or -S(-O)2-; exactly one linker moiety is -NRN-, or: exactly two linker moieties are -NRN-; exactly one linker moiety is -C(-X)-, and no linker moiety is -S(-O)2-; or: exactly one linker moiety is -S(-O)2-, and no linker moiety is -C(-X)-; no two adjacent linker moieties are -NRN-; X is independently -O or -S; each RN is independently -H or a substituent; A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.