Synthesis and SAR of novel tricyclic quinoxalinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)
Graphical abstract
Based on screening hit 1, a series of tricyclic quinoxalinones have been designed and evaluated for inhibition of PARP-1. Substitutions at the 7- and 8-positions of the quinoxalinone ring led to a number of compounds with good enzymatic and cellular potency. The tricyclic quinoxalinone class is sensitive to modifications of both the amine substituent and the tricyclic core. The synthesis and structure–activity relationship studies are presented.
References and notes (13)
Curr. Opin. Pharmacol.
(2006)et al.Drug News Perspect.
(2007)et al.Clin. Cancer Res.
(2007)- et al.
J. Clin. Oncol.
(2005) - et al.
J. Natl. Cancer Inst.
(2004) - et al.
Pharmacol. Rev.
(2002) - et al.
Biochem. J.
(2005)et al.Pharmacol. Res.
(2005)et al.Oncol. Rep.
(2004)et al.Biochemie
(1995) - et al.
Clin. Cancer Res.
(2007)
Cited by (97)
Accessing Chiral Pyrrolodiketopiperazines under Organocatalytic Conditions
2023, Organic LettersPoly lactide-co-glycolide encapsulated nano-curcumin promoting antagonistic interactions between HSP 90 and XRCC1 proteins to prevent cypermethrin-induced toxicity: An in silico predicted in vitro and in vivo approach
2022, Colloids and Surfaces B: BiointerfacesCitation Excerpt :Protein Data Bank (PDB) was considered as the ideal platform where the proteins of interest, heat shock protein 90 (HSP 90), p53, PARP and XRCC1 were downloaded. PDB IDs of the downloaded HSP 90, PARP, p53, and XRCC1 were 1YET [34], 3GJW [35], 1YC5 [36], 5E6Q [37] respectively. The protein of interest was prepared by removing water molecules and adding hydrogen atoms.
Catalyst-free aerobic radical cascade reactions of o-vinylphenylisocyanides with thiols to access 2-thio-substituted quinolines
2022, Organic Chemistry FrontiersAccess to quinolinones via DMAP-catalysed cascade reaction of 2-substituted benzoic acids with organic azides
2022, Chemical CommunicationsSynthesis of N-Aryl α-Ketoamides, α-Ketoesters, α-Ketothioesters and Their Applications in Quinoxalinone Preparation
2022, Asian Journal of Organic ChemistryFunctionalized quinoxalinones as privileged structures with broad-ranging pharmacological activities
2022, European Journal of Medicinal ChemistryCitation Excerpt :PARP-1 is the most prevalent and widely studied subtype in the nucleus [42]. Therefore, Miyashiro et al. obtained tricyclic quinoxalinone hit compound 24 as PARP-1 inhibitor through high-throughput screening (HTS), and further functionalized the 7- and 8-position with amine-containing side chains (Fig. 7) [43]. 7-Position substituted analogues were more effective, among which cyclic amine substituted compounds 25a-b exerted the highest potency.