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Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon

Darina Dadashevna Barkhatova 1
Darina Dadashevna Barkhatova
, 
Daniil Dmitrievich Zhukovsky 1
Daniil Dmitrievich Zhukovsky
, 
Christopher Heim 2, 3
Christopher Heim
, 
Samuel Maiwald 3
Samuel Maiwald
, 
Marcus D Hartmann 2, 3
Marcus D Hartmann
, 
Mikhail Yur'evich Krasavin 1, 4
Mikhail Yur'evich Krasavin
10.1016/j.mencom.2022.11.013
Published 2022-10-21
Communication , Volume 32, Issue 6, 747-749
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Barkhatova D. D. et al. Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon // Mendeleev Communications. 2022. Vol. 32. No. 6. pp. 747-749.
GOST all authors (up to 50) Copy
Barkhatova D. D., Zhukovsky D. D., Heim C., Maiwald S., Hartmann M. D., Krasavin M. Y. Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon // Mendeleev Communications. 2022. Vol. 32. No. 6. pp. 747-749.
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TY - JOUR
DO - 10.1016/j.mencom.2022.11.013
UR - https://mendcomm.colab.ws/publications/10.1016/j.mencom.2022.11.013
TI - Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon
T2 - Mendeleev Communications
AU - Barkhatova, Darina Dadashevna
AU - Zhukovsky, Daniil Dmitrievich
AU - Heim, Christopher
AU - Maiwald, Samuel
AU - Hartmann, Marcus D
AU - Krasavin, Mikhail Yur'evich
PY - 2022
DA - 2022/10/21
PB - Mendeleev Communications
SP - 747-749
IS - 6
VL - 32
ER -
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@article{2022_Barkhatova,
author = {Darina Dadashevna Barkhatova and Daniil Dmitrievich Zhukovsky and Christopher Heim and Samuel Maiwald and Marcus D Hartmann and Mikhail Yur'evich Krasavin},
title = {Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon},
journal = {Mendeleev Communications},
year = {2022},
volume = {32},
publisher = {Mendeleev Communications},
month = {Oct},
url = {https://mendcomm.colab.ws/publications/10.1016/j.mencom.2022.11.013},
number = {6},
pages = {747--749},
doi = {10.1016/j.mencom.2022.11.013}
}
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Barkhatova, Darina Dadashevna, et al. “Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon.” Mendeleev Communications, vol. 32, no. 6, Oct. 2022, pp. 747-749. https://mendcomm.colab.ws/publications/10.1016/j.mencom.2022.11.013.

Keywords

2-aminoglutarimide
Cereblon
E3 ubiquitin ligase
immunomodulatory drugs
isocyanides
oxo acids
Ugi reaction

Abstract

The glutarimide moiety, common in many immuno-modulatory drugs, was decorated with lactam and diamide side chains via two variants of the Ugi reaction, namely, with isocyanide, aldehyde and acid or with isocyanide and oxo acid. The resulting diastereomerically pure compounds were evaluated for their affinity towards the E3 ubiquitin ligase substrate receptor Cereblon.

References

1.
Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma
Quach H., Ritchie D., Stewart A.K., Neeson P., Harrison S., Smyth M.J., Prince H.M.
Leukemia, 2009
2.
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Fischer E.S., Böhm K., Lydeard J.R., Yang H., Stadler M.B., Cavadini S., Nagel J., Serluca F., Acker V., Lingaraju G.M., Tichkule R.B., Schebesta M., Forrester W.C., Schirle M., Hassiepen U., et. al.
Nature, 2014
3.
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke J., Udeshi N.D., Narla A., Grauman P., Hurst S.N., McConkey M., Svinkina T., Heckl D., Comer E., Li X., Ciarlo C., Hartman E., Munshi N., Schenone M., Schreiber S.L., et. al.
Science, 2014
5.
Bivalent Ligands for Protein Degradation in Drug Discovery
Scheepstra M., Hekking K.F., van Hijfte L., Folmer R.H.
Computational and Structural Biotechnology Journal, 2019
6.
PROTAC targeted protein degraders: the past is prologue
Békés M., Langley D.R., Crews C.M.
Nature Reviews Drug Discovery, 2022
7.
Replacing the phthalimide core in thalidomide with benzotriazole
Krasavin M., Bubyrev A., Kazantsev A., Heim C., Maiwald S., Zhukovsky D., Dar’in D., Hartmann M.D., Bunev A.
Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
8.
Ligands for cereblon: 2017–2021 patent overview
Kazantsev A., Krasavin M.
Expert Opinion on Therapeutic Patents, 2021
9.
E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points
Bricelj A., Steinebach C., Kuchta R., Gütschow M., Sosič I.
Frontiers in Chemistry, 2021
10.
Development of Potent and Selective Janus Kinase 2/3 Directing PG–PROTACs
Alcock L.J., Chang Y., Jarusiewicz J.A., Actis M., Nithianantham S., Mayasundari A., Min J., Maxwell D., Hunt J., Smart B., Yang J.J., Nishiguchi G., Fischer M., Mullighan C.G., Rankovic Z., et. al.
ACS Medicinal Chemistry Letters, 2022
11.
Chemical Ligand Space of Cereblon
Boichenko I., Bär K., Deiss S., Heim C., Albrecht R., Lupas A.N., Hernandez Alvarez B., Hartmann M.D.
ACS Omega, 2018
12.
10.1016/j.mencom.2022.11.013_b0060
Ugi
Angew. Chem., 1959
13.
10.1016/j.mencom.2022.11.013_b0065
Tsaloev
Tetrahedron Lett., 1800
16.
Sweet and Blind Spots in E3 Ligase Ligand Space Revealed by a Thermophoresis-Based Assay
Maiwald S., Heim C., Hernandez Alvarez B., Hartmann M.D.
ACS Medicinal Chemistry Letters, 2020
17.
Delineating the role of cooperativity in the design of potent PROTACs for BTK
Zorba A., Nguyen C., Xu Y., Starr J., Borzilleri K., Smith J., Zhu H., Farley K.A., Ding W., Schiemer J., Feng X., Chang J.S., Uccello D.P., Young J.A., Garcia-Irrizary C.N., et. al.
Proceedings of the National Academy of Sciences of the United States of America, 2018