Replacing the phthalimide core in thalidomide with benzotriazole

Krasavin, M; Bubyrev, A; Kazantsev, A; Heim, C; Maiwald, S; Zhukovsky, D; Dar'in, D; Hartmann, MD; Brunev, A

doi:10.1080/14756366.2021.2024525

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Replacing the phthalimide core in thalidomide with benzotriazole

MPS-Authors

/persons/resource/persons271516

Heim, C
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271554

Maiwald, S
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271510

Hartmann, MD
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Krasavin, M., Bubyrev, A., Kazantsev, A., Heim, C., Maiwald, S., Zhukovsky, D., et al. (2022). Replacing the phthalimide core in thalidomide with benzotriazole. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), 527-530. doi:10.1080/14756366.2021.2024525.

Cite as: https://hdl.handle.net/21.11116/0000-000A-3755-9

Abstract

The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4ACRBN E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.