Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery.

Autor: Kirichok AA; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine., Shton IO; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine., Pishel IM; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine., Zozulya SA; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine.; Taras Shevchenko National, University of Kyiv, Chemistry Department, Volodymyrska 64, 01601, Kyiv, Ukraine., Borysko PO; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine., Kubyshkin V; Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany., Zaporozhets OA; Taras Shevchenko National, University of Kyiv, Chemistry Department, Volodymyrska 64, 01601, Kyiv, Ukraine., Tolmachev AA; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine., Mykhailiuk PK; Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine.; Taras Shevchenko National, University of Kyiv, Chemistry Department, Volodymyrska 64, 01601, Kyiv, Ukraine.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2018 Apr 11; Vol. 24 (21), pp. 5444-5449. Date of Electronic Publication: 2018 Feb 15.
DOI: 10.1002/chem.201800193
Abstrakt: The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps-synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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