GB2462361A — Dihydropyridophthalazinone inhibitors of poly(ADP-ribose)polymerase (PARP) activity

USPTO Abstract

Dihydropyridophthalazinone inhibitors of poly(ADP-ribose)polymerase (PARP) activity8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3-(7H)-one compounds of formula (I) or isomers, stereoisomers, enantiomers, salts, solvates, chemically protected forms or pro-drugs thereof, wherein Y and Z are each independently selected from an optionally substituted aryl, heteroaryl or substitutent; R1, R2and R3are each independently selected from hydrogen, halogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, (NRARB)alkylene and (NRARB)carbonyl, wherein RAand RBare independently selected from hydrogen alkyl, cycloalkyl and alkylcarbonyl or together with the atom to which they are attached form a 3-10 membered heterocyclic ring optionally having one to three heteroatoms or heterofunctionalities; A and B are each independently selected from hydrogen, Br, Cl, F, I, OH, or an optionally substituted C1-C6alkyl, C3-C8cycloalkyl, alkoxy, alkoxyalkyl, wherein B is not OH; and R4and R5are each independently selected from hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl,hydroxyalkylene and (NRARB)alkylene. Such compounds are useful in the treatment of diseases, disorders and conditions that are ameliorated by the inhibition of poly(ADP-ribose) polymerase activity (PARP) activity particularly cancer. Pharmaceutical preparations and methods of preparation are also outlined.