Astex Therapeutics Limited

Eva Figueroa Navarro

Maria Grazia Carr

Miles Stuart Congreve

Christopher William Murray

Gianni Chessari

Martyn Frederickson

Alison Jo-Anne Woolford

Michael Alistair O'Brien

Andrew James Woodhead

Robert Downham

Theresa Rachel Phillips

Valerio Berdini

Steven Howard

Paul Graham Wyatt

Adrian Liam Gill

Gary Trewartha

David Charles Rees

Mladen Vinkovic

Theresa Rachel Early

Michael Alistair O'brien

Alison Jo-Ann Woolford

Valerio 436 Cambridge Science Park Berdini

The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein Ris hydroxy or hydrogen; Ris hydroxy; methoxy or hydrogen; provided that at least one of Rand Ris hydroxy; Ris selected from hydrogen; halogen; cyano; optionally substituted Chydrocarbyl and optionally substituted Chydrocarbyloxy; Ris selected from hydrogen; a group &#x2014;(O)&#x2014;Rwhere n is 0 or 1 and Ris an optionally substituted acyclic Chydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-Chydrocarbyl-amino; or Rand Rtogether form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NRRforms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The compounds have activity as Hsp90 inhibitors.

Hydroxybenzamide derivatives and their use as inhibitors of HSP90

The invention provides compounds of the general formula (I) which have activity as Hsp90 inhibitors.

Hydroxybenzamide derivatives and their use as inhibitors of Hsp90

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 provides a combination comprising an Hsp90 inhibitor compound of the formula (VII): or tautomer or salt thereof and one or more therapeutic agents selected from topoisomerase I inhibitors; antimetabolites; tubulin targeting agents; DNA binder and topoisomerase II inhibitors; alkylating agents; monoclonal antibodies; anti-hormones; signal transduction inhibitors; proteasome inhibitors; DNA methyl transferases; cytokines; retinoids and HDAC or HAT modulators.

Therapeutic combinations of hydroxybenzamide derivatives as inhibitors of HSP90

This invention provides methods for treating cancer, particularly hematopoietic tumors of lymphoid or myeloid lineage, prostate cancer, lung cancer, gastrointestinal stromal tumor, breast cancer and melanoma, which comprise administering to the mammal a compound, salt, hydrate, tautomer or N-oxide according to formula (I): and in particular, those of subgenus VIIa  These compounds inhibit or modulate the activity of the heat shock protein Hsp90.

Dihydroxyphenyl isoindolylmethanones

The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein Ris hydrogen; Ris hydroxy or methoxy; Ris selected from hydrogen; halogen; cyano; optionally substituted Chydrocarbyl and optionally substituted Chydrocarbyloxy; Ris selected from hydrogen; a group &#x2014;(O)&#x2014;Rwhere n is 0 or 1 and Ris an optionally substituted acyclic Chydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-Chydrocarbyl-amino; or Rand Rtogether form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NRRforms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The compounds have activity as Hsp90 inhibitors.

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

Compounds having the formula (I): and in particular, those of subgenus VIIa are disclosed as inhibits or modulators of the activity of the heat shock protein Hsp90. As such they are useful for treating cancer, particularly hematopoietic tumors of lymphoid or myeloid lineage, prostate cancer, lung cancer, gastrointestinal stromal tumor, breast cancer and melanoma.

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Cambridge, United Kingdom

Eva Figueroa Navarro