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Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands

Anna Alekseevna Ananeva 1
Anna Alekseevna Ananeva
, 
Grigoriy Pavlovich Kantin 1
Grigoriy Pavlovich Kantin
, 
Dmitry Viktorovich Dar’in 1, 2
Dmitry Viktorovich Dar’in
, 
Alexander Siyasatovich Bunev 3
Alexander Siyasatovich Bunev
, 
Sebastian Ebeling 4
Sebastian Ebeling
, 
Alexander Herrmann 4
Alexander Herrmann
, 
Marcus D Hartmann 4
Marcus D Hartmann
, 
Stanislav Alekseevich Kalinin 1
Stanislav Alekseevich Kalinin
, 
Olga Yurievna Bakulina 1
Olga Yurievna 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.7615
Published 2025-03-31
Communication , Volume 35, Issue 3, 285-288
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Ananeva A. A. et al. Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands // Mendeleev Communications. 2025. Vol. 35. No. 3. pp. 285-288.
GOST all authors (up to 50) Copy
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. Y. Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands // Mendeleev Communications. 2025. Vol. 35. No. 3. pp. 285-288.
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TY - JOUR
DO - 10.71267/mencom.7615
UR - https://mendcomm.colab.ws/publications/10.71267/mencom.7615
TI - Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands
T2 - Mendeleev Communications
AU - Ananeva, Anna Alekseevna
AU - Kantin, Grigoriy Pavlovich
AU - Dar’in, Dmitry Viktorovich
AU - Bunev, Alexander Siyasatovich
AU - Ebeling, Sebastian
AU - Herrmann, Alexander
AU - Hartmann, Marcus D
AU - Kalinin, Stanislav Alekseevich
AU - Bakulina, Olga Yurievna
PY - 2025
DA - 2025/03/31
PB - Mendeleev Communications
SP - 285-288
IS - 3
VL - 35
ER -
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@article{2025_Ananeva,
author = {Anna Alekseevna Ananeva and Grigoriy Pavlovich Kantin and Dmitry Viktorovich Dar’in and Alexander Siyasatovich Bunev and Sebastian Ebeling and Alexander Herrmann and Marcus D Hartmann and Stanislav Alekseevich Kalinin and Olga Yurievna Bakulina},
title = {Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands},
journal = {Mendeleev Communications},
year = {2025},
volume = {35},
publisher = {Mendeleev Communications},
month = {Mar},
url = {https://mendcomm.colab.ws/publications/10.71267/mencom.7615},
number = {3},
pages = {285--288},
doi = {10.71267/mencom.7615}
}
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Cite this
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Ananeva, Anna Alekseevna, et al. “Catalytic Castagnoli--Cushman reaction-based synthesis of tetrahydroisoquinolone--glutarimide dyads and their evaluation as potential cereblon ligands.” Mendeleev Communications, vol. 35, no. 3, Mar. 2025, pp. 285-288. https://mendcomm.colab.ws/publications/10.71267/mencom.7615.

Keywords

Castagnoli�Cushman reaction
glutarimide
homophthalic anhydride
imines
PROTAC
tetrahydroisoquinolones.

Abstract

A series of imines derived from α-aminoglutarimide and alhehydes RCHO was introduced into the In(OTf)3-catalyzed Castagnoli--Cushman reaction with homophthalic anhydrides thus yielding novel glutarimide--tetrahydroisoquinolone dyads with moderate yields. Carrying out the reaction at room temperature affords isomers with cis-orientation of the R substituent and carboxy group whereas heating to 80 °C promotes conversion into more stable trans-isomers. Some selected compounds were evaluated in vitro, revealing mild or no antiproliferative effects, and tested for cereblon-binding, with the bestperforming compound showing an affinity in the range of canonical cereblon ligands.

Funders

Russian Science Foundation
22-13-00005

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