1‐Azaspiro[3.3]heptane as a Bioisostere of Piperidine**-Reference-Cited by-同舟云学术

1‐Azaspiro[3.3]heptane as a Bioisostere of Piperidine**

Published:2023-11-14 Issue:51 Volume:62 Page:
ISSN:1433-7851
Container-title:Angewandte Chemie International Edition
language:en
Short-container-title:Angew Chem Int Ed

Author:

Kirichok Alexander A.¹²,Tkachuk Hennadii¹,Kozyriev Yevhenii¹³,Shablykin Oleh¹⁴,Datsenko Oleksandr¹,Granat Dmitry¹,Yegorova Tetyana²,Bas Yuliya P.²,Semirenko Vitalii¹,Pishel Iryna¹,Kubyshkin Vladimir¹,Lesyk Dmytro⁵,Klymenko‐Ulianov Oleksii⁵,Mykhailiuk Pavel K.¹²^ORCID

Affiliation:

1. Enamine Ltd Winston Churchill Str. 78 02094 Kyiv Ukraine

2. Taras Shevchenko National University of Kyiv Faculty of Chemistry Volodymyrska 60 01601 Kyiv Ukraine

3. Oles Honchar Dnipro National University Faculty of Chemistry 72 Gagarina Ave. 49010 Dnipro Ukraine

4. V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine Akademika Kukharya 1 02094 Kyiv Ukraine

5. Bienta Winston Churchill Str. 78 02094 Kyiv Ukraine

Abstract

Abstract1‐Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with alane produced 1‐azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent‐free analogue with high activity.

Funder

HORIZON EUROPE European Research Council

Publisher

Wiley

Subject

General Chemistry,Catalysis

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202311583

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