Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2- a ]pyridines derivatives as protein kinase inhibitors

Lawson, Marie; Rodrigo, Jordi; Baratte, Blandine; Thomas, Robert; Delehouzé, Claire; Lozach, Olivier; Ruchaud, Sandrine; Bach, Stéphane; Brion, Jean‐Daniel; Alami, Mouâd; Hamzé, Abdallah

doi:10.1016/j.ejmech.2016.07.040

Cited by 31 publications

(7 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Owing to the biological importance of imidazo[1,2‐ a ]pyridines derivatives, [123] Lawson et al [124] . in 2016 intended to explore new representatives on imidazo[1,2‐ a ]pyridines heterocyclic scaffolds and able to modulate kinase activity.…”

Section: Development Of Various Methods Towards the Synthesis Of Imidazo[12‐a]pyridinesmentioning

confidence: 99%

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

et al. 2022

View full text Add to dashboard Cite

This review focuses on providing comprehensive highlights of the recent synthetic pathways of imidazo[1,2‐a]pyridines, assisted through transition metal‐catalyzed reactions, multi‐component reactions, cyclization, condensation, microwave‐assisted reactions, heteroannular and photocatalytic reactions. Among the heterocyclic groups, imidazo[1,2‐a]pyridines are considered as privileged structures because of their occurrence in many natural products. In this review, we have summarized the recent advances in the synthesis of imidazo[1,2‐a]pyridines from 2016 to 2021 from various substrates. This review will provide new initiatives to the chemists towards the synthesis of imidazo[1,2‐a]pyridines and all frequent challenges associated with the reported methods.

show abstract

Section: Development Of Various Methods Towards the Synthesis Of Imidazo[12‐a]pyridinesmentioning

confidence: 99%

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The first series of imidazo[1,2‐a]pyridines reported in literature were synthesized as Clk1/Dyrk1A dual inhibitors for the treatment of AD. High throughput screening against a panel of kinases identified compound ( 40 ) as a lead for developing dual Clk1/Dyrk1A inhibitors, displaying IC 50 s of 1400 and 8900 nM against Clk1 and Dyrk1A, respectively 139 …”

Section: Clk1 Inhibitorsmentioning

confidence: 99%

An overview of cdc2‐like kinase 1 (Clk1) inhibitors and their therapeutic indications

ElHady

El-Gamil

Abadi

et al. 2022

Medicinal Research Reviews

View full text Add to dashboard Cite

Over the past decade, Clk1 has been identified as a promising target for the treatment of various diseases, in which deregulated alternative splicing plays a role. First small molecules targeting Clk1 are in clinical trials for the treatment of solid cancer, where variants of oncogenic proteins derived from alternative splicing promote tumor progression. Since many infectious pathogens hi-jack the host cell's splicing machinery to ensure efficient replication, further indications in this area are under investigation, such as Influenza A, HIV-1 virus, and Trypanosoma infections, and more will likely be discovered in the future. In addition, Clk1 was found to contribute to the progression of Alzheimer's disease through causing an imbalance of tau splicing products. Interestingly, homozygous Clk1 knockout mice showed a rather mild phenotype, opposed to what might be expected in view of the profound role of Clk1 in alternative splicing. A major drawback of most Clk1 inhibitors is their insufficient selectivity; in particular, Dyrk kinases and haspin were frequently identified as off-targets, besides the other Clk isoforms. Only few inhibitors were shown to be selective over Dyrk1A and haspin, whereas no Clk1 inhibitor so far achieved selectivity over the Clk4 isoform. In this review, we carefully compiled all Clk1 inhibitors from the scientific literature and summarized their structure-activity relationships (SAR). In addition, we critically discuss the available selectivity data

show abstract

“…Some of the reported pyridine molecules are selective toward topoisomerase inhibitors [7]. Some of the pyridine-conjugated derivatives were PIM-1 kinase inhibitors [8], human carbonic anhydrase inhibitors [9], proto-oncogene tyrosine-protein kinase (ROS) [10], ALK/ROS1 dual inhibitors, receptor tyrosine kinase (RTK) c-Met, epidermal growth factor receptor [11], EGFR and HER-2 kinase inhibitors, cyclin-dependent kinase (CDK) inhibitors [12], VEGFR-2 inhibitors [12], topoisomerases, phosphoinositide 3-kinase, maternal embryonic leucine zipper kinase (MELK), NF-κB inhibitors [13], etc. Considering all this information, exploration of these heterocycles is very important for the development of potential anticancer drug candidates.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Functions of Pyridine Heterocycles

Narasimhamurthy¹,

Kallesha²,

Mohan³

et al. 2023

Cytotoxicity - Understanding Cellular Damage and Response

View full text Add to dashboard Cite

Pyridine is a heterocyclic molecule with a nitrogen atom that is often found in nature. As a prosthetic group taking part in redox processes in the biological system, it plays an important function in many enzymes of the living system. Pyridine is an important pharmacophore, a privileged scaffold, and a superior heterocyclic system in drug development, with various applications in anticancer research because of its ability to work on significant receptors. Typically, it is the core of several currently available medicines. In the fight against cancer, many pyridine derivatives have been shown to inhibit kinases, androgen receptors, tubulin polymerization, topoisomerase enzyme, human carbonic anhydrase, and several other targets. Researchers are now concentrating on developing pyridine novel entities with other moieties for cancer therapy. This section presents pyridine derivative synthesis and biological expansions, as well as their target receptor sites.

show abstract

Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2- a ]pyridines derivatives as protein kinase inhibitors

Cited by 31 publications

References 52 publications

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

An overview of cdc2‐like kinase 1 (Clk1) inhibitors and their therapeutic indications

Anticancer Functions of Pyridine Heterocycles

Contact Info

Product

Resources

About