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Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction

Liliya R Khuzhakhmetova 1
Liliya R Khuzhakhmetova
, 
Anna Alekseevna Ananeva 1
Anna Alekseevna Ananeva
, 
Grigory Pavlovich Kantin 1
Grigory Pavlovich Kantin
, 
Dmitry Viktorovich Dar’in 1, 2
Dmitry Viktorovich Dar’in
,  , 
Sebastian Ebeling 4
Sebastian Ebeling
, 
Alexander Herrmann 4
Alexander Herrmann
, 
Marcus D Hartmann 4
Marcus D Hartmann
, 
Stanislav A Kalinin 1
Stanislav A Kalinin
, 
Olga Yu Bakulina 1
Olga Yu Bakulina
2 St. Petersburg Research Institute of Phthisiopulmonology, 191036 St. Petersburg, Russian Federation
3 Medicinal Chemistry Center, Togliatti State University, 445020 Togliatti, Russian Federation
4 Department of Protein Evolution, Max Planck Institute for Biology, 72076 Tübingen, Germany
10.71267/mencom.7543
Published 2025-01-24
Communication , Volume 35, Issue 1, 69-72
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Khuzhakhmetova L. R. et al. Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction // Mendeleev Communications. 2025. Vol. 35. No. 1. pp. 69-72.
GOST all authors (up to 50) Copy
Khuzhakhmetova L. R., Ananeva A. A., Kantin G. P., Dar’in D. V., Bunev A. S., Ebeling S., Herrmann A., Hartmann M. D., Kalinin S. A., Bakulina O. Yu. Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction // Mendeleev Communications. 2025. Vol. 35. No. 1. pp. 69-72.
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TY - JOUR
DO - 10.71267/mencom.7543
UR - https://mendcomm.colab.ws/publications/10.71267/mencom.7543
TI - Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction
T2 - Mendeleev Communications
AU - Khuzhakhmetova, Liliya R
AU - Ananeva, Anna Alekseevna
AU - Kantin, Grigory Pavlovich
AU - Dar’in, Dmitry Viktorovich
AU - Bunev, Alexander Siyasatovich
AU - Ebeling, Sebastian
AU - Herrmann, Alexander
AU - Hartmann, Marcus D
AU - Kalinin, Stanislav A
AU - Bakulina, Olga Yu
PY - 2025
DA - 2025/01/24
PB - Mendeleev Communications
SP - 69-72
IS - 1
VL - 35
ER -
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@article{2025_Khuzhakhmetova,
author = {Liliya R Khuzhakhmetova and Anna Alekseevna Ananeva and Grigory Pavlovich Kantin and Dmitry Viktorovich Dar’in and Alexander Siyasatovich Bunev and Sebastian Ebeling and Alexander Herrmann and Marcus D Hartmann and Stanislav A Kalinin and Olga Yu Bakulina},
title = {Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction},
journal = {Mendeleev Communications},
year = {2025},
volume = {35},
publisher = {Mendeleev Communications},
month = {Jan},
url = {https://mendcomm.colab.ws/publications/10.71267/mencom.7543},
number = {1},
pages = {69--72},
doi = {10.71267/mencom.7543}
}
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Cite this
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Khuzhakhmetova, Liliya R., et al. “Synthesis of α-(azidomethyl)glutarimide and its applicationin construction of potential Cereblon ligands via the CuAAC reaction.” Mendeleev Communications, vol. 35, no. 1, Jan. 2025, pp. 69-72. https://mendcomm.colab.ws/publications/10.71267/mencom.7543.
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Keywords

1
2
3-triazoles
alkynes
azides
Cereblon
click reaction
CuAAC
glutarimide
Pomalidomide.
PROTAC

Abstract

The Michael addition of tetramethylsilyl azide to 3-methylenepiperidine-2,6-dione afforded new glutarimide derivative, 3-(azidomethyl)piperidine-2,6-dione, which was introduced into the CuAAC click reaction with a variety of alkynes to afford thirty novel structurally diverse 1,2,3-triazoles. The cytotoxicity of the synthesized compounds was evaluated on multiple myeloma cell lines (MM1.S, KMS-12-PE), a leukemia cell line (NALM-6), and normal B-cells (WIL2-S) showing a noticeable effect on the MM1.S cell line. Selected compounds demonstrated significant Cereblon binding affinity in a microscale thermophoresis assay with one derivative outperforming the reference drug Pomalidomide.

Funders

Russian Science Foundation
22-13-00005

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