Synthesis and Design of Multi-Heterocyclic Molecules with Duoble 1,2,4-Triazole Motifs as Inhibitors of Cell Division Cycle Protein 25B Phosphatases

doi:10.11944/j.issn.1000-0518.2018.02.170004

Chinese Journal of Applied Chemistry ›› 2018, Vol. 35 ›› Issue (2): 154-164.DOI: 10.11944/j.issn.1000-0518.2018.02.170004

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Synthesis and Design of Multi-Heterocyclic Molecules with Duoble 1,2,4-Triazole Motifs as Inhibitors of Cell Division Cycle Protein 25B Phosphatases

ZHANG Chenglu(),WANG Jing,LI Yizheng,LI Chuanyin,SUN Xiaona

College of Chemistry and Chemical Engineering,Liaoning Normal University,Dalian,Liaoning 116029,China

Received:2017-01-03 Accepted:2017-04-14 Published:2018-02-01 Online:2018-01-29
Contact: ZHANG Chenglu
Supported by:
Supported by the Technology Research Program of Liaoning Provincial Department of Education(No.2009A426)

Abstract

Abstract:

Heterocyclic molecules containing 1,2,4-triazole motif are important for drug screening due to their better broad spectrum of bioactivities. For structure-activity relationship study, twenty-eight novel multi-heterocyclic molecules [TM1TM3(af)] and [TM4TM5(ae)] containing duo 1,2,4-triazole motifs were synthesized by the conjugation with piperazine and s-triazine, respectively. The structures of target molecules were confirmed via infrared(IR), proton nuclear magnetic resonance(¹H NMR) and high resolution mass spectrometry(HRMS). In order to investigate the effect of 4-amino substituent on 1,2,4-triazole for bioactivities, the comparison between compounds 6-morpholine-2,4-(5-thioether-4-amino-3-n-pentyl-1,2,4-triazole)-1,3,5-triazine(C), 6-pyrrole-2,4-(5-mercapto-4-amino-3-n-pentyl-1,2,4-triazole)-1,3,5-triazine(D) and target molecules were also performed. The inhibitory activities against cell division cycle protein 25B(Cdc25B) phosphatases of synthesized molecules were evaluated. Twenty one molecules exhibit good activities, and nine among them are more potent than the positive control Na₃VO₄.

Key words: 1,2,4-triazole, piperazine, s-triazine, cell division cycle protein 25B inhibitor

ZHANG Chenglu, WANG Jing, LI Yizheng, LI Chuanyin, SUN Xiaona. Synthesis and Design of Multi-Heterocyclic Molecules with Duoble 1,2,4-Triazole Motifs as Inhibitors of Cell Division Cycle Protein 25B Phosphatases[J]. Chinese Journal of Applied Chemistry, 2018, 35(2): 154-164.

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Synthesis and Design of Multi-Heterocyclic Molecules with Duoble 1,2,4-Triazole Motifs as Inhibitors of Cell Division Cycle Protein 25B Phosphatases

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