One-pot sequential C–N coupling and cross dehydrogenative couplings: synthesis of novel azole fused imidazo[1,2-a]pyridines

Pericherla, Kasiviswanadharaju; Khedar, Poonam; Khungar, Bharti; Kumar, Anil

doi:10.1039/c3cc39206f

Cited by 57 publications

(22 citation statements)

References 22 publications

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“…The synthesized quinazolinone based rhodamines are potent anti-cancerous agents 39 . Imidazole's and benzimidazoles are the functional precursors of polyazaheterocycles that are synthesized with the aid of microwave-mediated multi domino reactions MDRs 40,41 . New thiazolo [2,3-b] quinazolinone derivatives 5ab, 5aq and 5bq (Figure 1) are synthesized by microwave-assisted organic synthesis (MAOS) and multi-domino reaction (MDR).…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamic Simulations and Binding Free Energy Evaluations of Thiazolo-[2,3-b] Quinazolinone Derivatives With wtEGFR-TKD and "TMLR" Mutant EGFR-TKD

Mir

Nayak

2021

Preprint

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Cancer causes innumerable deaths every year globally. Breast cancer and non-small cell lung carcinoma (NSCLC) are the most prevalent worldwide. The epidermal growth factor receptor tyrosine kinases play a pivotal role in manifestations of cellular signals in carcinoma cells and thus are endorsed as therapeutic targets in cancer management. EGFR-TKD is a good option for the treatment of cancer, but the resistance shown by first-generation TKIs leads to hyperphosphorylation, overexpression, and mutations of EGFR-TKD. The new molecular scaffolds of thiazolo-[2,3-b] quinazolinones were evaluated against EGFR-TKD via molecular docking simulations and thereby linked with molecular dynamic simulations to identify the ligand stability with EGFR-TKD’s. The binding energy of thiazolo-[2,3-b] quinazolinones is approximately similar to that of reference molecules found against both wild type wtEGFR-TKD and EGFR-TKD mutant "TMLR" (T790M/L858R) in this study. According to ADMET analysis, thiazolo-[2,3-b] quinazolinone derivatives (5ab, 5aq, and 5bq) are safe. The stability was investigated at an atomistic level by molecular dynamic simulations, and the strength of the bindings was calculated by the molecular mechanics Poisson-Boltzmann surface areas continuum solvation MM-PBSA method. The RMSD, radius of gyration, and SASA trajectories were studied in detail. The ΔGbind generated by heterocyclic 5aq thiazolo-[2,3-b] quinazolinone was found to be -63.723 ± 0.419 kJ/mol against the EGFR-TKD mutant "TMLR" and it was -51.551 ± 0.409 kJ/mol against wtEGFR-TKD. This study concludes that the top ranked complexes 5ab, 5aq, and 5bq with both wild and mutated types of EGFR-TKD corroborate that thiazolo-[2,3-b] quinazolinone derivatives, like the FDA-approved drug erlotinib, may be potent inhibitors of EGFR-TKD for patients with NSCLC.

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Section: Resultsmentioning

confidence: 99%

Molecular Dynamic Simulations and Binding Free Energy Evaluations of Thiazolo-[2,3-b] Quinazolinone Derivatives With wtEGFR-TKD and "TMLR" Mutant EGFR-TKD

Mir

Nayak

2021

Preprint

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“…Cross dehydrogenative coupling/double C-H activation Recently, Kumar and coworkers have reported a one-pot approach involving C-N coupling and intramolecular C-C bond formation via double C-H activation for synthesis of azole-fused imidazo[1,2-a]pyridines 1.225a-c from the reaction of imidazo[1,2a]pyridines 1.223 with various azoles such as imidazoles, benzimidazoles, and 1,2,4-triazoles 1.224a-c, respectively. This method involves a one-pot approach with Ullmann type C-N coupling followed by intramolecular dehydrogenative cross coupling reaction (Scheme 66) [105,106]. …”

Section: Buchwald Cross-couplingmentioning

confidence: 99%

Recent synthetic scenario on imidazo[1,2-a]pyridines chemical intermediate

2015

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Of the biologically important benzene fused heterocycles, the most important are those containing a ring-junction nitrogen. The majority of ring junction systems do not occur naturally, but they have been important from a theoretical viewpoint, for preparation of potentially active analogues. The imidazo[1,2-a] pyridines are an important class of nitrogen ring junction heterocyclic compounds. They have huge applications in medicinal chemistry and drug molecule production. Thus, the initial discussion focuses on synthetic strategies of imidazo[1,2-a] pyridines, and later we disclose the reactivity of the imidazo[1,2-a]pyridines. This review is intended to summarize and discuss the most recent developments of synthesis and reactivity of imidazo[1,2-a]pyridines, mainly the contributions after 2007.

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“…In 2013, C-N coupling followed by an intramolecular dehydrogenative cross coupling of imidazo[1,2-a]pyridines 10 was successfully attempted. 13 This one-pot efficient protocol led to the synthesis of novel azole-fused imidazo[1,2a]pyridines 11 in good yields via double C-H activation in the presence of Pd(OAc) 2 and Cu(OAc) 2 as the oxidant (Scheme 5).…”

Section: Imidazo[12-a]pyridinesmentioning

confidence: 99%

An Update on Direct C–H Bond Functionalization of Nitrogen-Containing Fused Heterocycles

Aziz

Piguel

2017

Synthesis

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This report highlights the recent advances in direct C–H bond functionalization of 5,5- and 6,5-fused heterocycles containing at least two nitrogen atoms. Besides C–C bond formation, C–N, C–S, C–P, and C–Si bonds can also be created via a metal-catalyzed process. Some examples, where a C–H functionalization approach was applied for the synthesis of drug candidates, will be presented as well.1 Introduction2 C–H Functionalization Reactions of N-Containing Heterocycles2.1 Imidazo[1,2-a]pyridines2.2 Pyrrolo[1,2-a]pyrazines2.3 Imidazo[1,2-b]pyrazoles2.4 Imidazo[1,2-a]pyrimidines2.5 Imidazo[1,2-a]pyrazines and Imidazo[1,5-a]pyrazines2.6 Imidazo[1,2-b]pyridazines2.7 Imidazo[4,5-b]pyridines and Imidazo[4,5-c]pyridines2.8 Pyrazolo[3,4-b]pyridines2.9 Pyrazolo[1,5-a]pyrimidines2.10 Pyrrolo[2,3-d]pyrimidines and Pyrrolo[3,2-d]pyrimidines2.11 Imidazo[1,2-b][1,2,4]triazines2.12 Imidazo[1,2-b][1,2,4,5]tetrazines3 Outlook4 Conclusion

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One-pot sequential C–N coupling and cross dehydrogenative couplings: synthesis of novel azole fused imidazo[1,2-a]pyridines

Abstract: An efficient one-pot protocol has been developed using sequential C-N coupling and intramolecular dehydrogenative cross-couplings for the synthesis of azole fused imidazo[1,2-a]pyridine derivatives in good yields (62-78%).

Cited by 57 publications

References 22 publications

Molecular Dynamic Simulations and Binding Free Energy Evaluations of Thiazolo-[2,3-b] Quinazolinone Derivatives With wtEGFR-TKD and "TMLR" Mutant EGFR-TKD

Molecular Dynamic Simulations and Binding Free Energy Evaluations of Thiazolo-[2,3-b] Quinazolinone Derivatives With wtEGFR-TKD and "TMLR" Mutant EGFR-TKD

Recent synthetic scenario on imidazo[1,2-a]pyridines chemical intermediate

An Update on Direct C–H Bond Functionalization of Nitrogen-Containing Fused Heterocycles

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