5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl) isoquinolin-1-ones as isoform-selective inhibitors of poly (ADP-ribose) polymerase 2 (PARP-2)

PT Sunderland, ECY Woon, A Dhami…

Index: Sunderland, Peter T.; Woon, Esther C. Y.; Dhami, Archana; Bergin, Aoife B.; Mahon, Mary F.; Wood, Pauline J.; Jones, Louise A.; Tully, Sophie R.; Lloyd, Matthew D.; Thompson, Andrew S.; Javaid, Hashim; Martin, Niall M. B.; Threadgill, Michael D. Journal of Medicinal Chemistry, 2011 , vol. 54, # 7 p. 2049 - 2059

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Citation Number: 32

Abstract

PARP-2 is a member of the poly (ADP-ribose) polymerase family, with some activities similar to those of PARP-1 but with other distinct roles. Two series of isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors of PARP-2, using the structures of the catalytic sites of the isoforms. A new efficient synthesis of 5-aminoisoquinolin-1-one was developed, and acylation with acyl chlorides gave 5-acylaminoisoquinolin-1-ones. By ...