Astex Therapeutics Limited

Cancer Research Technology Limited

The Institute of Cancer Research: Royal Cancer Hospital

The Wellcome Trust Limited

Adrian Liam Gill

Valerio Berdini

Maria Grazia Carr

Paul Graham Wyatt

Michael Alistair O'Brien

Gary Trewartha

Alison Jo-Anne Woolford

Andrew James Woodhead

Theresa Rachel Early

Richard David Taylor

Miles Stuart Congreve

Andrew Madin

Christopher William Murray

Gordon Saxty

Steven Howard

Eva Figueroa Navarro

Owen Callaghan

Caroline Joy Springer

David Charles Rees

Richard Marais

Charlotte Mary Griffiths-Jones

Gilbert Besong

Emma Vickerstaffe

Mladen Vinkovic

Andrew Pike

Esteban Roman Vela

Rajdeep Kaur Nijjar

Gilbert Ebai Besong

Dan Niculescu-Duvaz

David Richard Newell

Ion Niculescu-Duvaz

Delphine Menard

John Francis Lyons

Neil Gallagher

Jayne Elizabeth Curry

Michael Alistair O'brien

Harmen Dijkstra

Catherine Gaulon

Richard Malcolm Marais

Alison Jo-Ann Woolford

Valerio 436 Cambridge Science Park Berdini

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3.  In formula (0):

3,4-disubstituted 1H-pyrazole compounds and their use as cyclin dependent kinase and glycogen synthase kinase-3 modulators

The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Bicyclic heterocyclic compounds as FGFR inhibitors

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof, and combinations thereof with other anti-cancer agents, for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. 

The invention provides a compound of the formula (I): or a salt, solvate, tautomer or N-oxide thereof, wherein M is selected from a group D1 and a group D2: and R', E, A and X are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, processes for making the compounds and the use of the compounds in the prophylaxis or treatment of a disease state mediated by a CDK kinase, GSK-3 kinase or Aurora kinase. 

Pyrazole compounds that modulate the activity of CDK, GSK and aurora kinases

The invention relates to new bicyclic heterocyclic derivative compounds of Formula (I), to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. The compounds of Formula (I) are inhibitors of FGFR, VEGFR or PDGFR.

Imidazo[1,2-a]pyridine compounds for use in treating cancer

A method for the treatment of: A. a disease state or condition mediated by a kinase wh ich is BCR-abl, VEGFR, PDGFR, EGFR, FLT3, JAK, C-abl, PDK1, Chk, FGFR, Ret, Eph, or Src; or B. a cancer in which the cancer cells thereof contain a drug resistant kinase mutation which is: (a) a threonine gatekeeper mutation; or (b) a drug-resistant gatekeeper mutation; or (c) an imatinib resistant mutation; or (d) a nilotinib resistant mutation; or (e) a dasatinib resistant mutation; or (f) a T670l mutation in KIT; or (g) a T674l mutation in PDGFR; or (h) T790M mutation in EGFR; or (i) a T315l mutation in abl; or C. a cancer which expresses a mutated molecular target which is a mutated form of BCRabl, c-kit, PDGF, EGF receptor or ErbB2; which method comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula (l or l'): or a salt, solvate, tautomer or N-oxide thereof. 

Pharmaceutical compounds

The present invention relates to FGFR pharmacophores, and in particular to compounds which are capable of binding to FGFR with greater affinity than their binding to VEGFR and methods of identifying such compounds using the pharmacophore. The present invention further relates to compositions, methods and uses of the compounds and the pharmacophores disclosed herein.

FGFR pharmacophore compounds

The invention provides compounds of the formula (I): The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases and are therefore useful to treat cancer and viral diseases.

Benzimidazole derivatives and their use as protein kinase inhibitors

The present invention pertains to certain 6-carboaryloxy-pyrazin-2-yl-carboaryl-amines of the following formula, and pharmaceutically acceptable salts thereof, which, inter alia, inhibit RAF (e.g., B-RAF) activity, inhibit cell proliferation, treat cancer, etc., wherein Q is independently &#x2014;N&#x2550;; Ris independently a group of the formula -J-L-Z; -JL-Z is independently &#x2014;NH&#x2014;Z; Z is independently Ccarboaryl and is independently unsubstituted or substituted; Ris independently &#x2014;H; Ris independently a group of the formula &#x2014;W&#x2014;Y; W is independently &#x2014;O&#x2014;; Y is independently Ccarboaryl and is independently unsubstituted or substituted; and Ris independently &#x2014;H. The present invention also pertains to pharmaceutical compositions comprising such compounds. 

6-carboaryl-oxy-pyrazin-2-yl-carboaryl-amines and compositions comprising said 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

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0):

Growing community of inventors

Cheshire, United Kingdom

Adrian Liam Gill