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Synthesis 2022; 54(11): 2677-2686
DOI: 10.1055/s-0040-1719907
paper

Synthesis and Biological Investigation of 1,2,4-Triazolo[4,3-a]azines as Potential HSF1 Inductors

Polina O. Serebrennikova 
a   Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira str., 620002, Ekaterinburg, Russian Federation
b   Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22 S. Kovalevskoy str., 620108, Ekaterinburg, Russian Federation
,
Irina A. Utepova  ∗
a   Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira str., 620002, Ekaterinburg, Russian Federation
b   Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22 S. Kovalevskoy str., 620108, Ekaterinburg, Russian Federation
,
Oleg N. Chupakhin 
a   Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira str., 620002, Ekaterinburg, Russian Federation
b   Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22 S. Kovalevskoy str., 620108, Ekaterinburg, Russian Federation
,
Irina V. Guzhova
c   Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky av., 194064, St-Petersburg, Russian Federation
,
Elena R. Mikhaylova
c   Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky av., 194064, St-Petersburg, Russian Federation
,
Andrey P. Antonchick
d   Department of Chemistry and Forensics, School of Science and Technology, Nottingham Trent University, Clifton Lane, NG11 8NS, Nottingham, UK
› Author AffiliationsThe research was supported by Ministry of Science and Higher Education of Russia, Research Project N 075-15-2020-795, local identifier 13.1902.21.0027.
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Abstract

Derivatives of fused 1,2,4-triazines containing heterocyclic and metallocene fragments were obtained by one-pot oxidative cyclization of heterocyclic hydrazones in the presence of hypervalent iodine(III) reagents. For 1,2,4-triazolo[4,3-a]azines, the ability to activate HSF1 was investigated. The obtained compounds were shown to increase the degree of HSF1 activation. It was shown that the 1,2,4-triazines can be used to induce Hsp70 expression and decrease the extent of mutant HTT aggregate formation.

Key words

azoloazine - hypervalent iodine(III) - cyclization - HSF1 inductors - heteroaromatic - metallocene

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1719907.
  • Supporting Information


Publication History

Received: 29 November 2021

Accepted after revision: 04 February 2022

Article published online:
17 March 2022

© 2022. Thieme. All rights reserved

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