Synthesis of N-substituted benzo[c][1,7]- and benzo[c][1,8] phenanthrolin-(5H)-6-ones through a Pd-mediated Suzuki–Miyaura heteroaryl-aryl coupling reaction

Genès, Constance; Michel, Sylvie; Tillequin, François; Porée, François‐Hugues

doi:10.1016/j.tet.2009.09.110

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…Since the C-ring of the indenoisoquinolines does not offer attractive locations for the incorporation of nitrogen, it was expanded to a six-membered ring using an additional nitrogen atom. These studies were supported by the previously reported biological interest in nitidine chloride ( 14 ), topovale ( 70 ), and structurally related heterocyclic systems. , The resulting compounds had moderate biological activities, as represented by the dibenzo[ c , h ]naphthyridine systems 71 (Top1 ++, MGM 4.3 μM) and 72 (Top1 +++, MGM 3.3 μM). Although the overall MGM values for 71 and 72 were moderate, they retained potent anticancer activities in a number of cell lines.…”

Section: Synthesis and Biological Evaluation Of Azaindenoisoquinolinessupporting

confidence: 69%

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Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

Cushman

2021

J. Med. Chem.

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The discovery that certain indenoisoquinolines inhibit the religation reaction of DNA in the topoisomerase I-DNA-indenoisoquinoline ternary complex led to a structure-based drug design research program which resulted in three representatives that entered Phase I clinical trials in cancer patients at the National Cancer Institute. This has stimulated a great deal of interest in the design and execution of new synthetic pathways for indenoisoquinoline production. More recently, modulation of the substitution pattern and chemical nature of substituents on the indenoisoquinoline scaffold has resulted in a widening scope of additional biological targets, including RXR, PARP-1, MYC promoter G-quadruplex, topoisomerase II, estrogen receptor, VEGFR-2, HIF-1α, and tyrosyl DNA phosphodiesterases 1 and 2. Furthermore, convincing evidence has been advanced supporting the potential use of indenoisoquinolines for the treatment of diseases other than cancer. The rapidly expanding indenoisoquinoline knowledge base has provided a firm foundation for further advancements in indenoisoquinoline chemistry, pharmacology, and therapeutics.

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Section: Synthesis and Biological Evaluation Of Azaindenoisoquinolinessupporting

confidence: 69%

“…These studies were supported by the previously reported biological interest in nitidine chloride ( 14), 17 topovale (70), 69 and structurally related heterocyclic systems. 70,71 The resulting compounds had moderate biological activities, as represented by the dibenzo [c,h]…”

Section: ■ Studies Of the Effect Of The Substituents On The Aromatic ...mentioning

confidence: 99%

Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

Cushman

2021

J. Med. Chem.

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“…Tandem 1,3-halogen migration/functionalization/Suzuki couplings of 1 were accomplished using ( Z )-3-iodopent-2-en-1-ol and 2-iodobenzyl alcohol to yield the heterocyclic dihydroxepins 11 and 12 . Finally, halogen migration followed by reaction with 2-iodoaniline and subsequent Pd-catalyzed coupling/oxidation gave the biologically active phenanthridine core of 13 …”

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confidence: 99%

Copper-Catalyzed Recycling of Halogen Activating Groups via 1,3-Halogen Migration

2012

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A Cu(I)-catalyzed 1,3-halogen migration reaction effectively recycles an activating group by transferring bromine or iodine from a sp2 to a benzylic carbon with concomitant borylation of the Ar-X bond. The resulting benzyl halide can be reacted in the same vessel under a variety of conditions to form an additional carbon-heteroatom bond. Cross-over experiments using an isotopically enriched bromide source support intramolecular transfer of Br. The reaction is postulated to proceed via a Markovnikov hydrocupration of the o-halostyrene, oxidative addition of the resulting Cu(I) complex into the Ar-X bond, reductive elimination of the new sp3 C-X bond, and final borylation of an Ar-Cu(I) species to turn over the catalytic cycle.

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“…A number of closely related, fused tetracyclic systems have previously been described. This list includes molecules such as nitidine chloride ( 6 ), , topovale ( 7 ), benzo[ c ]phenanthrolinone 8 , and dibenzo[ c , h ][1,5]naphthyridine 9 . Molecules 6 – 9 and their derivatives were found to be capable of binding to the Top1–DNA cleavage complex (Top1–DNAcc) or intercalating into the DNA double helix, and their development as anticancer agents and DNA probes have therefore been pursued. − …”

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confidence: 99%

Dibenzo[c,h][1,5]naphthyridinediones as Topoisomerase I Inhibitors: Design, Synthesis, and Biological Evaluation

et al. 2012

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Dibenzo[c,h][1,5]naphthyridinediones were prepared via a novel synthetic pathway. The compounds were designed as topoisomerase I (Top1) inhibitors based on the indenoisoquinoline series of drugs. The results of biological evaluation demonstrate that, unlike very closely related dibenzo[c,h][1,6]naphthyridinediones, dibenzo[c,h][1,5]naphthyridinediones retain the Top1 inhibitory activity of similarly substituted indenoisoquinolines.

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Synthesis of N-substituted benzo[c][1,7]- and benzo[c][1,8] phenanthrolin-(5H)-6-ones through a Pd-mediated Suzuki–Miyaura heteroaryl-aryl coupling reaction

Cited by 12 publications

References 24 publications

Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

Copper-Catalyzed Recycling of Halogen Activating Groups via 1,3-Halogen Migration

Dibenzo[c,h][1,5]naphthyridinediones as Topoisomerase I Inhibitors: Design, Synthesis, and Biological Evaluation

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