Events9th International Electronic Conference on Medicinal Chemistry
Event submissions
Published
with-doi10.3390/ECMC2023-15657 (registering DOI)
This submission belongs to the session S4. New Small molecules as drug candidates of the event 9th International Electronic Conference on Medicinal Chemistry
Published date
01 Nov, 2023
Academic Editor
author-avatarMaria Emília Sousa
Citation
Lidia Vasilchenko, Nikolay Li-Zhulanov, Konstantin Volcho, Alexandra Zakharenko, Olga Lavrik, Nariman Salakhutdinov, Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme, in Proceedings of 9th International Electronic Conference on Medicinal Chemistry, 1 November–30 November 2023, MDPI: Basel, Switzerland, doi: 10.3390/ECMC2023-15657
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Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme

Lidia Vasilchenko 1
Nikolay Li-Zhulanov 1
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Konstantin Volcho 1
Alexandra Zakharenko 2
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Olga Lavrik 2
Nariman Salakhutdinov 1
1. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia
2. Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia
Abstract

Earlier in our laboratory, amide derivatives of octahydrochromene were obtained by a three-component Prince-Ritter reaction. These compounds exhibited inhibiting activity against the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) in the low micromolar range [1]. Based on molecular modeling results, it was proposed that acetamide derivatives of octahydrochromene 3, which contain an arylpiperazine moiety, may exhibit inhibitory activity against Tdp1.

The purpose of this work is the synthesis of chiral acetamide derivatives of octahydrochromene with an arylpiperazine moiety, starting from 2-chloroacetamide, p-tolyloctahydrochromene 1, and substituted arylpiperazines 2.

The alkylation reaction was carried out in acetonitrile by boiling in the presence of К2СО3, after purification by column chromatography the yields of the target compounds ranged from 11 to 89%.

Compound 3а didn’t exhibit inhibitory activity against Tdp1, (IC50 > 50µM), while compounds 3b-d showed inhibitory activity ranged from 19.3 to 10.3 µМ.

Keywords
tyrosyl-DNA phosphodiesterase 1 inhibitors
octahydro-2H-chromene
alkylation reaction
Manuscript
Vasilchenko_Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme .doc.pdf
Oral Presentation
Poster_Vasilchenko_Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme.ppt
Poster
Poster_Vasilchenko_Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme.pdf
Poster_Vasilchenko_Synthesis of acetamide derivatives of octahydrochromene with arylpiperazine moiety, perspective inhibitors of the Tdp1 enzyme.pdf
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