1,6-Naphthyridin-2(1H)-ones: Synthesis and Biomedical Applications

Oliveras, Juan Marcos; Bellacasa, Raimon Puig de la; Estrada‐Tejedor, Roger; Teixidó, Jordi; Borrell, José I.

doi:10.3390/ph14101029

Cited by 3 publications

(4 citation statements)

References 66 publications

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“…The other aromatic protons resonated in the region of δ 7.22-8.89. From its 13 C NMR spectrum 27 carbons were confirmed. All the spectral and analytical details assigned the structure of the compound as 4-chloro-N-(9-ethyl-9H-carbazol-3-yl)-5-methylbenzo[h] [1,6]naphthyridin-2-amine (5 a) (Scheme 1).…”

Section: Synthesis Of 24-dichlorobenzo[h]naphthyridine From 4-aminoqu...mentioning

confidence: 98%

“…[6][7][8][9][10] PDK1 inhibitors represent a promising target for anticancer drugs in small molecules. [9][10][11][12] Among all nitrogen heterocycles, 1,6-naphthyridine analogues [13,14] are important class of compounds possessing diverse types of biological properties. [15,16] Recently, 1,4-dihydro-4-oxo-1,6-naphthyridine analogues have been described as antibacterial agents.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2‐Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

Prabha¹,

Satheeshkumar

Nasif

et al. 2022

ChemistrySelect

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The present work emphasizes the utility of 2,4‐dichloro‐5‐methylbenzo[h][1,6]naphthyridine as starting precursors. The reaction of 2,4‐dichloro‐5‐methylbenzo[h][1,6]naphthyridine with a variety of aliphatic and aromatic amines yielded 2‐amino substituted 2,4‐dichlorobenzo[h]naphthyridines. All the compounds were examined for their in vitro anticancer activity against six human cancer lines and docked with PDK1 inhibitors. The structure‐activity relationship studies are revealed that the compounds holding aminocarbazole moiety and triazole amine moiety improve the activity profile. All the structures of synthesized compounds were optimized at B3LYP‐D3/6‐31G(d) level in the water. Furthermore, the electronic properties and biological reactivity of the synthesized compounds are explored using computational techniques.

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Section: Synthesis Of 24-dichlorobenzo[h]naphthyridine From 4-aminoqu...mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2‐Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

Prabha¹,

Satheeshkumar

Nasif

et al. 2022

ChemistrySelect

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“…1,8-Naphthyridine C-nucleoside and their base-pairing properties have been reported [36]. Among these structures, naphthyridinones are also well known for their biological properties [37]. Only the 1,8-naphthyridinones have been particularly studied as nucleobase analogues.…”

Section: Introductionmentioning

confidence: 99%

1H-1,2,3-triazolyl-1,6-naphthyridin-7(6H)-ones as Potential Fluorescent Nucleoside Analogues: Synthesis and Optical Properties

Beghennou,

Rondot,

Corcé

et al. 2024

Molecules

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In this article, we present the synthesis and the optical properties of three original molecules as potential fluorescent ribonucleoside analogues incorporating a 1,6-naphthyridin-7(6H)-one scaffold as a fluorescent nucleobase and a 1,2,3-triazole as a linkage. The nucleosides were prepared via a Cu alkyne-azide cycloaddition (CuAAC) reaction between a ribofuranosyl azide and a 4-ethynylpyridine partner. Construction of substituted 1,6-naphthyridin-7(6H)-ones was achieved through two additional steps. Optical property studies were investigated on nucleoside analogues. Powerful fluorescence properties have been evidenced with a remarkable change of emissivity depending on the polarity of the solvent, making these molecules suitable as a new class of artificial fluorescent nucleosides for investigating enzyme binding sites as well as probing nucleic acids. In addition, we are convinced that such analogues could be of great interest in the search for new antiviral or antitumoral drugs based on nucleosides.

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“…Herein, focusing on the covalent interaction with specific amino acid Cys552, the diverse heterocycles were designed and biologically evaluated (Figure ). As a result, the 1,6-naphthyridin-2(1 H )-one scaffold was selected to develop as potent and selective FGFR4 inhibitors, owing to its good physicochemical properties, − potent inhibition, and good selectivity for FGFR4. Finally, A34 possessed robust inhibition and selectivity against FGFR4, with preferable pharmacokinetic (PK) properties.…”

Section: Introductionmentioning

confidence: 99%

Discovery of 1,6-Naphthyridin-2(1H)-one Derivatives as Novel, Potent, and Selective FGFR4 Inhibitors for the Treatment of Hepatocellular Carcinoma

Zhang

Wang

et al. 2022

J. Med. Chem.

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Fibroblast growth factor receptor 4 (FGFR4) has been identified as a potential target due to its transmission of the FGF19 signaling pathway, which is critical to hepatocellular carcinoma (HCC). Therefore, focusing on the specific Cys552 of FGFR4 subtype, we designed and synthesized a novel family of 1,6-naphthyridin-2(1H)-one derivatives as potent and highly selective FGFR4 inhibitors. Through detailed structural optimizations, the representative compound A34 exhibited improved FGFR4 inhibitory capability and selectivity and excellent anti-proliferative activities against FGFR4-dependent HCC cell lines. Additionally, A34 demonstrated remarkable antitumor efficacy in a Hep-3B HCC xenograft model, with favorable pharmacokinetic properties, and low risk of hERG toxicity. A34 also showed moderate inhibitory activities against the FGFR4 V550L mutant in vitro, which indicates that it has the potential as a novel anticancer agent for HCC.

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1,6-Naphthyridin-2(1H)-ones: Synthesis and Biomedical Applications

Cited by 3 publications

References 66 publications

Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2‐Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2‐Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

1H-1,2,3-triazolyl-1,6-naphthyridin-7(6H)-ones as Potential Fluorescent Nucleoside Analogues: Synthesis and Optical Properties

Discovery of 1,6-Naphthyridin-2(1H)-one Derivatives as Novel, Potent, and Selective FGFR4 Inhibitors for the Treatment of Hepatocellular Carcinoma

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