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The application of click chemistry in the synthesis of agents with anticancer activity.

Ma N, Wang Y, Zhao BX, Ye WC, Jiang S - Drug Des Devel Ther (2015)

Bottom Line: The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility.This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly.The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, People's Republic of China ; Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People's Republic of China ; Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.

ABSTRACT
The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents.

No MeSH data available.


Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.Abbreviation: Abl, Abelson.
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f16-dddt-9-1585: Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.Abbreviation: Abl, Abelson.

Mentions: Li et al designed a series of 3-(1H-1,2,3-triazol-1-yl)benzamide derivatives as new Bcr-Abl inhibitors by using combinational strategies of bio-isosteric replacement, scaffold hopping, and conformational constraint with the applications of click chemistry in 2012. The 1,2,3-triazole was utilized as a new linker between the heterocyclic moiety (the so-called head region) and the methylphenyl group (middle part) of the inhibitors. The new Bcr-Abl inhibitors showed significant inhibition against a broad spectrum of Bcr-Abl mutants including the most refractory gatekeeper T315I mutation. The most potent compound 30 (Figure 16) strongly inhibited the kinase activities of Bcr-AblWT and Bcr-AblT315I with mean IC50 values of 0.60 nM and 1.12 nM, respectively.49


The application of click chemistry in the synthesis of agents with anticancer activity.

Ma N, Wang Y, Zhao BX, Ye WC, Jiang S - Drug Des Devel Ther (2015)

Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.Abbreviation: Abl, Abelson.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362898&req=5

f16-dddt-9-1585: Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.Abbreviation: Abl, Abelson.
Mentions: Li et al designed a series of 3-(1H-1,2,3-triazol-1-yl)benzamide derivatives as new Bcr-Abl inhibitors by using combinational strategies of bio-isosteric replacement, scaffold hopping, and conformational constraint with the applications of click chemistry in 2012. The 1,2,3-triazole was utilized as a new linker between the heterocyclic moiety (the so-called head region) and the methylphenyl group (middle part) of the inhibitors. The new Bcr-Abl inhibitors showed significant inhibition against a broad spectrum of Bcr-Abl mutants including the most refractory gatekeeper T315I mutation. The most potent compound 30 (Figure 16) strongly inhibited the kinase activities of Bcr-AblWT and Bcr-AblT315I with mean IC50 values of 0.60 nM and 1.12 nM, respectively.49

Bottom Line: The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility.This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly.The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, People's Republic of China ; Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People's Republic of China ; Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.

ABSTRACT
The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents.

No MeSH data available.