Sentinel Oncology Limited

Cancer Research Technology Limited

Astex Therapeutics Limited

The Institute of Cancer Research: Royal Cancer Hospital

Millennium Pharmaceuticals Limited

Dainippon Pharmaceutical Company, Limited

Cascadian Therapeutics, Inc.

Robert George Boyle

David Winter Walker

Ian James Collins

Richard Justin Boyce

Valerio Berdini

Gordon Saxty

Paul Graham Wyatt

Steven Woodhead

Robert Downham

Michelle Dawn Garrett

Marinus Leendert Verdonk

Scott Peterson

John Caldwell

Francine Farouz

Hannah Fiona Sore

Robin Arthur Ellis Carr

Alastair Donald

Tatiana Faria Da Fonseca

Cong Hung Vo

Thomas Glanmor Davies

Michael Cherry

John Francis Lyons

Neil Thomas Thompson

Fuminori Sato

Mitsue Notake

Takashi Deguchi

Ryotaro Shiratake

Buichi Fujitani

Kyla Merriom Thompson

Akihiko Kiyoshi

Graham Andrew Showell

Sukhbinder Singh Klair

Hassan Julien Imogai

Yayoi Honda

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 which inhibit or modulate the activity of Chk-1 kinase and which are useful in the treatment of cancer. The compounds have the general formula (1): and salts, N-oxides and tautomers thereof, wherein m is 2, 3 or 4; n is 0 or 1; Qis selected from a bond; C(&#x2550;O); S(O); SO; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety Rand the nitrogen atom. N, wherein (a) one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two Calkyl groups; and/or (b) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by a cyclopropane-1,1-diyl or 1,1-cyclobutanediyl group; and/or (c) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by C(&#x2550;O), S(O), or SO, provided that Qcontains no more than one C(&#x2550;O), S(O), or SOmoiety; Ris selected from hydrogen, methyl, chlorine and bromine; Ris selected from hydrogen, methyl, methoxy and a group &#x2014;(O)-Q-R; Ris selected from hydrogen, a group Hyd, a group &#x2014;O-Hydand a group &#x2014;(O)-Q-R; provided that when one of Rand Ris &#x2014;(O)-Q-R, the other is selected from hydrogen, methoxy and methyl; and Ris selected from amino, NH-Hyd, N(Hyd); and a non-aromatic carbocyclic or heterocyclic ring of 4 to 7 ring members containing 0, 1, 2 or 3 heteroatom ring members selected from O, N and S and oxidized forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R. Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.

Pharmaceutically active pyrazine derivatives

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 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 &#x3b1; 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, RR, Rand Rare as defined in the claims, wherein the compound is for use in: (a) the treatment or prophylaxis of a disease or condition in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase P70S6K is indicated; and/or (b) the treatment of a subject or patient population in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase P70S6K is indicated. 

Purine and deazapurine derivatives as pharmaceutical compounds

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

Growing community of inventors

Cambridge, United Kingdom

Robert George Boyle