compound, methods of inhibiting raf activity 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 ameliorated by raf inhibition, and of treating a proliferative condition

摘要

MOBILE, IN VITRO OR IN VIVO, USE OF A COMPOUND, AND METHODS OF TREATING A DISEASE OR CONDITION WHICH IS IMPROVED BY RAF INHIBITION, AND TREATING A PROLIFERATIVE CONDITION. The present invention relates to certain compounds of imidazo-4,5-b-pyridin-2-one and oxazole-4,5-b-pyridin-2-one and analogs thereof, which, inter alia, inhibit RAF activity. (eg, B-RAF), inhibit cell proliferation, treat cancer, etc. and more particularly to compounds of formula (I): wherein: J is independently -O- or -NR¬ N1¬-; R¬ N1¬ present is independently -H or a substituent; R¬ N2¬ is independently -H or a substituent; Y is independently -CH = or -N =; Q is independently - (CH ~ 2 ~) ~ j ~ -M- (CH ~ 2 ~) ~ 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 -CH-2 -; each of R¬ P1¬, R¬ P2¬, R¬ P3¬ and R¬ P4¬ is independently -H or a substituent; and additionally R¬ P1¬ and R¬ P2¬ when together can 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 -CH ~ 2 ~ -, -NR¬ N¬-, -C (= X) - or -S (= O) ~ 2 ~ -; exactly one linker portion is -NR¬ N¬-, or: exactly two linker portions are -NR¬ N¬-; 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) -; two nonadjacent linker moieties are -NR¬ N¬-; X is independently = O or = S; each R¬ N¬ is independently -H or a substituent; A is independently: C 6-14 ~ carbaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; 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 relates to 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 ameliorated by inhibition of RAF, RTK, etc., proliferative conditions such as cancer (eg, colorectal cancer, melanoma), etc. Original Title: "IMIDAZO ¢ 4,5-B! PIRIDIN-2-ONA AND OXAZOLO ¢ 4,5-B! PYRIDIN-2-ONA COMPOUNDS AND THESE ANALOGUES AS THERAPEUTIC COMPOUNDS".