Cancer Research Technology Limited

Astex Therapeutics Limited

Kudos Pharmaceuticals Limited

Other

Ian Robert Hardcastle

Bernard Thomas Golding

Roger John Griffin

David Richard Newell

Niall Morrison Barr Martin

Graeme Cameron Murray Smith

Nicola Curtin

Duncan Charles Miller

Celine Florence Cano

Hilary Alan Calvert

Christopher Norbert Johnson

Steven Howard

Gianni Chessari

Ildiko Maria Buck

David Charles Rees

Kim Louise Hirst

Emiliano Tamanini

Laurent Jean Martin Rigoreau

James Daniel Osborne

Jeffrey David St Denis

Dale Robert Mitchell

Rhian Sara Holvey

Benjamin David Cons

Joanne Peach

Benjamin Paul Whittaker

David Wyn Watson

Martin Edward Mäntylä Noble

Arwel Lewis

Martin Noble

Keith Allan Menear

Eric Valeur

Marc Geoffrey Hummersone

Paul Workman

Florence Irene Raynaud

Bernard Paul Nutley

Xiao-ling Fan Cockcroft

Kappusamy Saravanan

Christiane Riedinger

Anna Frances Watson

Vincent Junior Ming-lai Loh

Martin E M Noble

Mark Frigerio

Hendrika Maria Gerarda Willems

Per Kallblad

John Lunec

Alan H Calvert

Marine Desage-El Murr

Tristan Reuillon

Stephanie Myers

Lauren Molyneux

Laurent Rigoreau

Sarah Cully

The invention provides a compound of formula (I): or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Isoindolinone inhibitors of the MDM2-P53 interaction having anticancer activity

Isoindolinone inhibitors of the MDM2-p53 interaction having anticancer activity

A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.

Therapeutic agents

The invention provides compounds of formula (I) or a tautomer, stereoisomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds are useful for the prophylaxis or treatment of a disease state or condition mediated by ERK5, in particular cancers.

Pyrrolcarboxamide derivatives for the inhibition of ERK5

A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53. 

A compound of formula or a prodrug and/or a pharmaceutically acceptable salt thereof, wherein X is O, N or S; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alloy substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; and R-R, is used to represent groups R, R, Rand Rwhich are H, OH, alkyl, alkoxy, alkylamine, hydroxyalkyl, halo, CF, NH, NO, COOH, C&#x2550;O.

Isoindolin-1-one derivatives

A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: Rand Rare independently selected from hydrogen, an optionally substituted Calkyl group, Cheterocyclyl group, or Caryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; Q is &#x2014;NH&#x2014;C(&#x2550;O)&#x2014; or &#x2014;O&#x2014;; Y is an optionally substituted Calkylene group; X is selected from SRor NRR, wherein, R, or Rand Rare independently selected from hydrogen, optionally substituted Calkyl, Caryl, or Cheterocyclyl groups, or Rand Rmay together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; if Q is &#x2014;O&#x2014;, X is additionally selected from &#x2014;C(&#x2550;O)&#x2014;NRR, wherein Rand Rare independently selected from hydrogen, optionally substituted Calkyl, Caryl, or Cheterocyclyl groups, or Rand Rmay together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and if Q is &#x2014;NH&#x2014;C(&#x2550;O)&#x2014;, &#x2014;Y&#x2014;X may additionally be selected from Calkyl.

DNA-PK inhibitors

Compounds of formula I: wherein A, B and D are respectively selected from the group consisting of:

The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein Rand Rare independently hydrogen, an optionally substituted Calkyl group, Cheterocyclyl group, or Caryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CRand O, O and CR'and NR&#x2033;and N, where the unsaturation is in the appropriate place in the ring, and where one of Rand Ror R&#x2032;is an optionally substituted Cheteroaryl or Caryl group, and the other of Rand Ror R&#x2032;is H, or Rand Ror R&#x2033;together are &#x2014;A&#x2014;B&#x2014;, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein:

The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein Rand Rare independently hydrogen, an optionally substituted Calkyl group, Cheterocyclyl group, or Caryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CRand O, O and CR'and NR&#x2033;and N, where the unsaturation is in the appropriate place in the ring, and where one of Rand Ror R&#x2032;is an optionally substituted Cheteroaryl or Caryl group, and the other of Rand Ror R&#x2032;is H, or Rand Ror R&#x2033;together are -A-B&#x2014;, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

Growing community of inventors

Hexham, United Kingdom

Ian Robert Hardcastle