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

Title: 1‐Azaspiro[3.3]heptane as a Bioisostere of Piperidine**
Authors: Kirichok, Alexander A.; Tkachuk, Hennadii; Kozyriev, Yevhenii; Shablykin, Oleh; Datsenko, Oleksandr; Granat, Dmitry; Yegorova, Tetyana; Bas, Yuliya P.; Semirenko, Vitalii; Pishel, Iryna; Kubyshkin, Vladimir; Lesyk, Dmytro; Klymenko‐Ulianov, Oleksii; Mykhailiuk, Pavel K.
Contributors: HORIZON EUROPE European Research Council
Source: Angewandte Chemie International Edition ; volume 62, issue 51 ; ISSN 1433-7851 1521-3773
Publisher Information: Wiley
Publication Year: 2023
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: 1‐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, ClO 2 S−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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1002/anie.202311583
Availability: https://doi.org/10.1002/anie.202311583; https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202311583
Rights: http://creativecommons.org/licenses/by-nc/4.0/
Accession Number: edsbas.7D2AC302
Database: BASE