Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1)

…, K Chun, BY Joe, JS Park, YC Kim, JS Choi…

Index: Park, Chun-Ho; Chun, Kwangwoo; Joe, Bo-Young; Park, Ji-Seon; Kim, Young-Chul; Choi, Ji-Soo; Ryu, Dong-Kyu; Koh, Seong-Ho; Cho, Goang Won; Kim, Seung Hyun; Kim, Myung-Hwa Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 7 p. 2250 - 2253

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Citation Number: 8

Abstract

Highly potent poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1, 2- dihydro-4H-thiopyrano [3, 4-c] quinolin-5 (6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC50= 42nM, ED50= 220nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.