3361-22-6Relevant academic research and scientific papers
Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2)
Yu, Le-Mao,Hu, Zhu,Chen, Yu,Ravji, Azhar,Lopez, Sophia,Plescia, Caroline B.,Yu, Qian,Yang, Hui,Abdelmalak, Monica,Saha, Sourav,Agama, Keli,Kiselev, Evgeny,Marchand, Christophe,Pommier, Yves,An, Lin-Kun
, p. 777 - 796 (2018)
Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered enzyme specifically repairing topoisomerase II (TOP2)-mediated DNA damage. It has been shown that inhibition of TDP2 synergize with TOP2 inhibitors. Herein, we report the discovery of the furoquinolinedione chemotype as a suitable skeleton for the development of selective TDP2 inhibitors. Compound 1 was identified as a TDP2 inhibitor as a result of screening our in-house compound library for compounds selective for TDP2 vs. TDP1. Further SAR studies provide several selective TDP2 inhibitors at low-micromolar range. The most potent compound 74 shows inhibitory activity with IC50 of 1.9 and 2.1 μM against recombinant TDP2 and TDP2 in whole cell extracts (WCE), respectively.
IMIDAZOPYRIDAZINE COMPOUNDS
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Page/Page column 113-114, (2008/06/13)
The present invention relates to novel substituted imidazo[1,2-b] pyridazine compounds of Formula (I) pharmaceutical compositions thereof, and the use such compounds as corticotropin releasing factor 1 (CRF1) receptor antagonists in the treatment of psychiatric disorders and neurological diseases.
