Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).
Chun-Ho Park, Kwangwoo Chun, Bo-Young Joe, Ji-Seon Park, Young-Chul Kim, Ji-Soo Choi, Dong-Kyu Ryu, Seong-Ho Koh, Goang Won Cho, Seung Hyun Kim, Myung-Hwa Kim
Index: Bioorg. Med. Chem. Lett. 20(7) , 2250-3, (2010)
Full Text: HTML
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 (IC(50) = 42 nM, ED(50) = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.2010 Elsevier Ltd. All rights reserved.
Related Compounds
Related Articles:
Cellulose derivatives synthesized via isocyanate and activated ester pathways in homogeneous solutions of lithium chloride/N, N-dimethylacetamide. Williamson SL and McCormick CL.
[J. Macromol. Sci., Pure Appl. Chem. 35(12) , 1915-27, (1998)]
Electronic substituent effects on hydrogen-bonding motifs modulate supramolecular polymerisation. Pellizzaro ML, et al.
[RSC Advances 3(9) , 3103-8, (2013)]