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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.
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f20-dddt-9-1585: Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.

Mentions: The family of fibroblast growth factor receptor (FGFR) is one of the 20 subclasses of receptor tyrosine kinases, consisting of four homologous receptors numbered FGFR1–4.62 FGFR3 can act as an oncogene in various cancers.63–65 Le Corre et al reported a library of pyrido[2,3-d]pyrimidines as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP-binding site in 2010. This library was built up with an efficient step of click chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogs they synthesized, more than half exhibited 55%–89% inhibition of in vitro FGFR3 kinase activity at 2 μM, and one (34, Figure 20) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells. Investigation also showed that the targeted region of the ATP-binding site accepts 1,2,3-triazole moiety, with a preference for positively charged substituents.66


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.
© Copyright Policy
Related In: Results  -  Collection

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

f20-dddt-9-1585: Chemical structures of protein tyrosine kinase inhibitors synthesized via click chemistry.
Mentions: The family of fibroblast growth factor receptor (FGFR) is one of the 20 subclasses of receptor tyrosine kinases, consisting of four homologous receptors numbered FGFR1–4.62 FGFR3 can act as an oncogene in various cancers.63–65 Le Corre et al reported a library of pyrido[2,3-d]pyrimidines as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP-binding site in 2010. This library was built up with an efficient step of click chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogs they synthesized, more than half exhibited 55%–89% inhibition of in vitro FGFR3 kinase activity at 2 μM, and one (34, Figure 20) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells. Investigation also showed that the targeted region of the ATP-binding site accepts 1,2,3-triazole moiety, with a preference for positively charged substituents.66

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.