Astex Therapeutics Limited

Glaxosmithkline Intellectual Property Development Limited

Cancer Research Technology Limited

The Institute of Cancer Research: Royal Cancer Hospital

Thomas Glanmor Davies

Alison Jo-Anne Woolford

James Francis Callahan

Jeffrey Charles Boehm

Ian James Collins

Gordon Saxty

Thomas Daniel Heightman

Jeffrey K Kerns

David Norton

Charlotte Mary Griffiths-Jones

Robert George Boyle

Brent W McCleland

Hong Nie

Joseph E Pero

Michelle Dawn Garrett

Hendrika Maria Gerarda Willems

Marinus Leendert Verdonk

Steven Howard

Maria Grazia Carr

Hongxing Yan

Tindy Li

Peng Li

Roderick S Davis

Hendrika Maria Willems

The present invention relates to biaryl pyrazole compounds of Formula (I) methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.

Biaryl pyrazoles as NRF2 regulators

The present invention relates to arylcyclohexyl pyrazole compounds of Formula (I) methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.

Arylcyclohexyl pyrazoles as NRF2 regulators

The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.

Nrf2 regulators

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 (I) having ROCK kinase and/or protein kinase p70S6K 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 R1 and 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; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; Ris an aryl or heteroaryl group; and R, R, Rand Rare as defined in the claims. 

Pharmaceutical compounds

Growing community of inventors

Cambridge, United Kingdom

Thomas Glanmor Davies