Cancer Research Technology Limited

Astex Therapeutics Limited

The Institute of Cancer Research: Royal Cancer Hospital

Harmen Dijkstra

Caroline Joy Springer

Richard Marais

Dan Niculescu-Duvaz

Delphine Menard

Ion Niculescu-Duvaz

Adrian Liam Gill

Richard David Taylor

Arnaud Nourry

Esteban Roman Vela

Lawrence Davies

Catherine Gaulon

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. 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.

Imidazo[4, 5-B]pyridin-2-one and oxazolo[4, 5-B] pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds

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 &#x2014;O&#x2014; or &#x2014;NR&#x2014;; R, if present, is independently &#x2014;H or a substituent; Ris independently &#x2014;H or a substituent; Y is independently &#x2014;CH&#x2550; or &#x2014;N&#x2550;; Q is independently &#x2014;(CH)&#x2014;M&#x2014;(CH)&#x2014; 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 &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;NH&#x2014;, &#x2014;NMe&#x2014;, or &#x2014;CH&#x2014;; each of R, R, R, and Ris independently &#x2014;H or a substituent; and additionally Rand Rtaken together may be &#x2014;CH&#x2550;CH&#x2014;CH&#x2550;CH&#x2014;; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently &#x2014;CH&#x2014;, &#x2014;NR&#x2014;, &#x2014;C(&#x2550;X)&#x2014;, or &#x2014;S(&#x2550;O)&#x2014;; exactly one linker moiety is &#x2014;NR&#x2014;, or: exactly two linker moieties are &#x2014;NR&#x2014;; exactly one linker moiety is &#x2014;C(&#x2550;X)&#x2014;, and no linker moiety is &#x2014;S(&#x2550;O)&#x2014;; or: exactly one linker moiety is &#x2014;S(&#x2550;O)&#x2014;, and no linker moiety is &#x2014;C(&#x2550;X)&#x2014;; no two adjacent linker moieties are &#x2014;NR&#x2014;; X is independently &#x2550;O or &#x2550;S; each Ris independently &#x2014;H or a substituent; A is independently: Ccarboaryl, Cheteroaryl, Ccarbocyclic, Cheterocyclic; 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. 

Imidazo[4,5-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-one compounds and analogs thereof as therapeutic compounds

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Maarssen, Netherlands

Harmen Dijkstra