DNA-PK inhibitors

• Main Authors: NIALL MORRISON BARR MARTIN, DAVID RICHARD NEWELL, LAURENT JEAN MARTIN RIGOREAU, BERNARD THOMAS GOLDING, HILARY ALAN CALVERT, BERNARD PAUL NUTLEY, GRAEME CAMERON MURRAY SMITH, XIAO-LING FAN COCKCROFT, NICOLA JANE CURTIN, ROGER JOHN GRIFFIN, VINCENT JUNIOR MING-LAI LOH, PAUL WORKMAN, IAN ROBERT HARDCASTLE, FLORENCE RAYNAUD
• Format: Patent
• Language: English
• Published: 02.02.2005
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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 R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl 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 CR4 and O, O and CR′4 and NR″4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R3 and R4 or R′4 is an optionally substituted C3-20 heteroaryl or C5-20 aryl group, and the other of R3 and R4 or R′4 is H, or R3 and R4 or R″4 together are -A-B-, 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.