Sentinel Oncology Limited

Cancer Research Technology Limited

Astex Therapeutics Limited

The Institute of Cancer Research: Royal Cancer Hospital

Cascadian Therapeutics, Inc.

David Winter Walker

Robert George Boyle

Valerio Berdini

Ian James Collins

Gordon Saxty

Paul Graham Wyatt

Steven Woodhead

Richard Justin Boyce

Robert Downham

Scott Peterson

Marinus Leendert Verdonk

John Caldwell

Francine Farouz

Tatiana Faria Da Fonseca

Hannah Fiona Sore

Robin Arthur Ellis Carr

Cong Hung Vo

Alastair Donald

Steven John Woodhead

The invention provides compounds of the formula (3): The compounds are useful in the treatment of cancers.

Pyrrole derivatives as PLK1 inhibitors

This invention relates to compounds that inhibit or modulate the activity of Chk-1 kinase. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds.

Pharmaceutical compounds

The invention provides compounds of the formula (3): or a pharmaceutically acceptable salt or tautomer thereof, wherein:Z is a 5-membered heteroaryl ring containing one or two nitrogen ring members and optionally one further heteroatom ring member selected from N and O;ring X is a benzene or pyridine ring;ring Y is a benzene, pyridine, thiophene or furan ring;Aris an optionally substituted benzene, pyridine, thiophene or furan ring;m is 0, 1 or 2;n is 0, 1 or 2;Ris selected from various substituents:Ris selected from hydrogen and a Chydrocarbon group;Ris selected from hydrogen and a Chydrocarbon group;Ris selected from various substituents;Ris selected from various substituents;Aris an optionally substituted phenyl, pyridyl or pyridone group;Ris a group Q-R&#x2014;R;Qis absent or is a Csaturated hydrocarbon linker;Ris selected from O; C(O); C(O)O; CONR; N(R)CO; N(R)CONR, NR; and SONR;Ris selected from hydrogen and various substituents;and Ris selected from R. The compounds are useful in the treatment of cancers.

The invention provides compound that inhibit or modulate the activity of p70S6 kinase, the compounds being of the formula (1): or a salt, tautomer or N-oxide thereof;wherein: The compounds are useful in medicine, for example in the treatment of a disease or condition selected from cancers, neurodevelopmental diseases and neurodegenerative diseases.

2-aminoquinazoline derivatives as P70S6 kinase inhibitors

The invention provides compounds for use in the treatment of a disease or condition selected from brain disorders and triple-negative breast cancer, the compounds being of the formula (1): or a salt or tautomer thereof;wherein:

Modulators of the p70S6 kinase for use in the treatment of brain disorders and triple-negative breast cancer

The invention provides compounds of the formula (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between Rand NRRand a maximum chain length of 4 atoms extending between E and NRR, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom &#x3b1; with respect to the NRRgroup and provided that the oxo group when present is located at a carbon atom &#x3b1; with respect to the NRRgroup; Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

Pyrazole derivatives as protein kinase modulators

The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR; J-Jis N&#x2550;C(R), (R)C&#x2550;N, (R)N&#x2014;C(O), (R)C&#x2014;C(O), N&#x2550;N or (R)C&#x2550;C(R); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Qis a bond or a saturated Chydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRor NRCO where Ris hydrogen or methyl, or Ris a Calkylene chain linked to R or a carbon atom of Qto form a cyclic moiety; and wherein the carbon atoms of the linker group Qmay optionally bear one or more substituents selected from fluorine and hydroxy; Qis a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Qis other than a bond; G is hydrogen, NRR, OH or SH provided that when E is aryl or heteroaryl and Qis a bond, then G is hydrogen; Ris hydrogen or an aryl or heteroaryl group, with the proviso that when Ris hydrogen and G is NRR, then Q is a bond; and R, R, R, Rand Rare as defined in the claims. 

Ortho-condensed pyridine and pyrimidine derivatives (e.g., purines) as protein

The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR; J-Jis N&#x2550;C(R), (R)C&#x2550;N, (R)N&#x2014;C(O), (R)C&#x2014;C(O), N&#x2550;N or (R)C&#x2550;C(R); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Qis a bond or a saturated Chydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRor NRCO where Ris hydrogen or methyl, or Ris a Calkylene chain linked to Ror a carbon atom of Qto form a cyclic moiety; and wherein the carbon atoms of the linker group Qmay optionally bear one or more substituents selected from fluorine and hydroxy; Qis a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Qis other than a bond; G is hydrogen, NRR, OH or SH provided that when E is aryl or heteroaryl and Qis a bond, then G is hydrogen; Ris hydrogen or an aryl or heteroaryl group, with the proviso that when Ris hydrogen and G is NRR, then Qis a bond; and R, R, R, Rand Rare as defined in the claims. 

Ortho-condensed pyridine and pyrimidine derivatives (e.g., purines) as protein kinases inhibitors

The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein Xis N or N(O); Xis N or CH; Q is a Calkylene group; Ris selected from hydrogen, Chydrocarbyl and hydroxy-Chydrocarbyl; R, Rand Rare the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Aris an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Aris an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.

Substituted benzotriazines and quinoxalines as inhibitors of P7OS6 kinase

The invention provides compounds of the formula (I) having protein kinase B inhibiting activity:  Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (Ic) or salts, tautomers or N-oxides thereof. 

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Linton, United Kingdom

David Winter Walker