Phthalazinone derivatives

• Main Authors: ASHWORTH, ALAN, JACKSON, STEPHEN PHILIP, MENEAR, KEITH ALLAN, COCKCROFT, XIAO-LING FAN, MARTIN, NIALL MORRISON BARR, MATTHEWS, IAN TIMOTHY WILLIAMS, KERRIGAN, FRANK, LOH, VINCENT M, SMITH, GRAEME CAMERON MURRAY
• Format: Patent
• Language: English
• Published: 29.08.2008
• 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 present disclosure relates to phthalazinone derivatives, and their use as pharmaceuticals. In particular the present invention relates to the use of these compounds to inhibit the activity of the enzyme poly (ADP-ribose)polymerase, also known as poly (ADP-ribose)synthase and poly ADP-ribosyltransferase, commonly referred to as PARP. More specifically the disclosure relates to a compound of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY ; If X = NRX then n is 1 or 2 and if X = CRXRY then n is 1; Rx is selected from the group consisting of H, optionally substituted C1-20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, C3-C20 heterocyclyl, amido, thioamido, ester,acyl, and sulfonyl groups; Ry is selected from H, hydroxyl, amino; Or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.