1‐Azaspiroheptane as a Bioisostere of Piperidine

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, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie 2023-12, Vol.135 (51)
Main 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, Oleksii Klymenko‐Ulianov, Mykhailiuk, Pavel K
Format: Article
Language:English
Subjects:
Alkenes
Amides
Bupivacaine
Chemistry
Cycloaddition
Heptanes
Isocyanates
Piperidine
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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, 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.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202311583