compound, pharmaceutical composition, methods for preparing a pharmaceutical composition, for inhibiting raf activity in a cell, in vitro or in vivo, for inhibiting cell proliferation, in vitro or in vivo, and for treating a disease or condition, and, use of a compound

摘要

COMIPOSTO, PHARMACEUTICAL COMPOSITION, METHODS FOR PREPARING A PHARMACEUTICAL COMPOSITION, TO INHIBIT RAF ACTIVITY IN A CELL, IN VITRO OR IN VIVO, TO INHIBIT CELLULAR PROLIFERATION, IN VITRO OR IN VIVO, AND TO TREAT, USE, OR TREAT A USE, OF A COMPOUND. The present invention concerns certain compounds of imidazo [4,5-b] pyridin-2-one and oxazolo [4,5-b] pyridin-2-one and its analogs, which inter alia inhibit RAF activity (for example, B RAF), inhibit cell proliferation, treat cancer, etc., and more particularly to the compounds of the formulas: where: J is independently -O- or ~ NR ^ NI ^ -; R1 N1 if present, is independently -H or a substituent; R is independently -H or a substituent; Y is independently -CH = or -N =; Q is independently - (CH ~ 2 ~) ~ j ~ -M- (CH ~ 2 ~) k- where: 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 -CH ~ 2 ~ -; each of R ^ P1 ^, R ^ P2 ^, R ^ P5 ^ and R ^ P4 ^ is independently -H or a substituent; and in addition R ^ P1 ^ and R ^ P2 ^ when together they can be CH = CH-CH = CH-; and in addition R ^ P1 ^ and R ^ P5 ^ when together they can be CH = CH-CH = CH; L is independently: a linking group formed by a chain of 2, 3 or 4 linking portions; each connecting moiety is independently CH ~ 2 ~ -, -NR ^ N- ^, - C (= X) - or -S (= O) ~ 2 ~ -; or: exactly one connecting moiety is -NR ^ N- ~, or: exactly two connecting moieties are -NR ~ N- ~; or: exactly one connecting portion is -C (= X) - and no connecting portion is S (= O) ~ 2 ~, or: exactly one connecting portion is S (= O) ~ 2 ~ and no connecting portion is -C (= X) -; neither of two adjacent connecting portions is -NR ^ N- ^; X is independently = O or = S; each R ^ N ^ is independently -H or a substituent; A is independently: C ~ 6-14 ~ carbonaryl, C ~ 5-14 ~ heteroaryl, C ~ 3-12 ~ carbocyclic, C ~ 3-12 ~ heterocyclic; and is independently unsubstituted or substituted; and salts, solvates, amides, esters, ethers, N-oxides, chemically protected and prodrug forms of the same pharmaceutically acceptable. The present invention also concerns pharmaceutical compositions comprising such compounds and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF activity (e.g., B-RAF), to inhibit tyrosine activity receptor kinase (RTK), to inhibit cell proliferation and to treat diseases and conditions that are improved by inhibiting RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.