1269762-02-8Relevant articles and documents
Synthesis of 4-alkyl-, 4-aryl- and 4-arylamino-5-aminoisoquinolin-1-ones and identification of a new PARP-2 selective inhibitor
Sunderland, Peter T.,Dhami, Archana,Mahon, Mary F.,Jones, Louise A.,Tully, Sophie R.,Lloyd, Matthew D.,Thompson, Andrew S.,Javaid, Hashim,Martin, Niall M. B.,Threadgill, Michael D.
, p. 881 - 891 (2011/04/22)
The considerable interest in substituted isoquinolin-1-ones related to 5-aminoisoquinolin-1-one (5-AIQ) as drugs points to a need for an efficient and straightforward synthesis of the 4,5-disubstituted bicycles. Bromination of 5-nitroisoquinolin-1-one gave 4-bromo-5-nitroisoquinolin-1-one but neither this nor 5-amino-4-bromoisoquinolin-1-one would participate in Pd-catalysed couplings. Protection of the lactam as 1-methoxy- and 1-benzyloxy-4-bromo-5- nitroisoquinolines, however, permitted Stille, Suzuki and Buchwald-Hartwig couplings to take place in high yields, insensitive to electronic demands and severe steric bulk in the arylboronic acids. Lithiation of 4-bromo-1-methoxy-5- nitroisoquinoline and quench with iodomethane gave 1-methoxy-4-methyl-5- nitroisoquinoline in low yield. Demethylation of the 1-methoxy-4-substituted-5- nitroisoquinolines with hydrogen bromide gave 4-substituted-5-nitroisoquinolin- 1-ones, whereas hydrogenolytic debenzylation was achieved with simultaneous reduction of the 5-nitro group. 5-Amino-4-(4-trifluoromethylphenyl)isoquinolin- 1-one was identified as a new potent and selective inhibitor of poly(ADP-ribose)polymerase-2 (PARP-2).
