Synthesis and structure-activity relationship studies of original cyclic diadenosine derivatives as nanomolar inhibitors of NAD kinase from pathogenic bacteria

Clément, David A.; Gelin, Muriel; Leseigneur, Clarisse; Huteau, Valérie; Mondange, Lou; Pons, Jean-Luc; Dussurget, Olivier; Lionne, Corinne; Labesse, Gilles; Pochet, Sylvie

doi:10.1016/j.ejmech.2022.114941

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…The potent compound 22 was developed and the macrocyclization was performed by intramolecular amide bond (Figure 5D). Compound 22 is active at 55 nM on recombinant NADK from L. monocytogenes (LmNADK1) and represents the best NADK-binder described to date [106].…”

Section: Nicotinamide Adenine Dinucleotide (Nad) Analogues To Target ...mentioning

confidence: 99%

Adenine, a key player in biology and medicinal chemistry

Fillion,

Vichier-Guerre,

Arimondo

2024

Comptes Rendus. Chimie

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Adenine is one of the most ubiquitous heterocycles in life. In addition of being one of the four nucleobases constituting DNA and RNA, adenine is also contained in many biological molecules (ATP, SAM, NAD, cAMP, coA . . . ) that have fundamental roles in the functioning of living systems, e.g. energy source, cofactors of enzymes and proteins. As such, the adenine has naturally become a privileged scaffold explored in medicinal chemistry for biomedical applications. Many chemical modifications and Structure-Activity Relationships studies have been carried out on the adenine scaffold to result in potent analogues with various biological activities. Today, numerous adenine-based inhibitors are used to treat a wide range of diseases including cancer, viral and bacterial diseases. This review aims to introduce the adenine and discuss adenine-based inhibitors, their design and use for different therapeutic targets through examples of drugs and compounds that reached clinical and preclinical trials.

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Section: Nicotinamide Adenine Dinucleotide (Nad) Analogues To Target ...mentioning

confidence: 99%

Adenine, a key player in biology and medicinal chemistry

Fillion,

Vichier-Guerre,

Arimondo

2024

Comptes Rendus. Chimie

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“…Nosyl groups have been used in the synthesis of polyfunctional nitrogen-containing molecules, including pharmaceuticals and natural products. 5 One of the weaknesses of the nosyl group is lability toward reducing agents or organometallic species. 6 Even under typical hydrogenation conditions with a palladium catalyst, the nitro moiety of the nosyl group is reduced to an amino group.…”

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confidence: 99%

Fluorinated 2,6-Xylenesulfonyl Group: A Protective Group for Amines

et al. 2023

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The Missing Link(er): A Roadmap to Macrocyclization in Drug Discovery

Brudy,

Walz,

Spiske

et al. 2024

J. Med. Chem.

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Macrocycles are one of nature's preferred choices to generate large but cell-permeable bioactive molecules. Macrocyclization is increasingly prominent in medicinal chemistry beyond natural products, especially for difficult-to-drug targets. However, strategies to best exploit the potential of macrocycles are only beginning to emerge. Here we survey drug discovery campaigns from the past decade that cumulated in advanced macrocyclic drug-like compounds or drug candidates. Most macrocycles were conceived by ring closing based on U-or C-shaped bioactive conformations observed in co-crystal structures. We focus on the key step from linear precursors to the first macrocycle and the follow-up optimization of the resulting macrocyclic scaffold. Conformational control recurrently emerged as a key factor for macrocycle properties and linkers as an opportunity for optimization. With increasingly challenging drug targets, we expect these trends to become more prominent and relevant. ■ SIGNIFICANCE • Summary of illustrative examples of how linear molecules can be converted into macrocycles. • Direct comparison of linear and macrocyclic ligands and their properties and analysis of underlying molecular driving forces. • Structure-based analysis of the key transition points from linear lead compounds to macrocycles in contemporary drug discovery programs. • Analysis and guidelines for linker design as an important area for the optimization of macrocycles.

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Synthesis and structure-activity relationship studies of original cyclic diadenosine derivatives as nanomolar inhibitors of NAD kinase from pathogenic bacteria

Cited by 3 publications

References 42 publications

Adenine, a key player in biology and medicinal chemistry

Adenine, a key player in biology and medicinal chemistry

Fluorinated 2,6-Xylenesulfonyl Group: A Protective Group for Amines

The Missing Link(er): A Roadmap to Macrocyclization in Drug Discovery

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