Open Access
Synlett 2017; 28(06): 695-700
DOI: 10.1055/s-0036-1589472
letter
© Georg Thieme Verlag Stuttgart · New York

Intensified Microwave-Assisted N-Acylation Procedure – Synthesis and Activity Evaluation of TRPC3 Channel Agonists with a 1,3-Dihydro-2H-benzo[d]imidazol-2-one Core

Gema Guedes de la Cruz
a   Institute of Chemistry, University of Graz and NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria   Email: toma.glasnov@uni-graz.at
,
Barbora Svobodova
b   Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria   Email: klaus.groschner@medunigraz.at
,
Michaela Lichtenegger
b   Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria   Email: klaus.groschner@medunigraz.at
,
Oleksandra Tiapko
b   Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria   Email: klaus.groschner@medunigraz.at
,
Klaus Groschner*
b   Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria   Email: klaus.groschner@medunigraz.at
,
Toma Glasnov*
a   Institute of Chemistry, University of Graz and NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria   Email: toma.glasnov@uni-graz.at
› Author Affiliations
Further Information

Publication History

Received: 23 September 2016

Accepted after revision: 14 November 2016

Publication Date:
08 December 2016 (online)


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Abstract

Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H-benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed. Compared to the few conventional protocols, a drastic reduction in processing time from ca. 2 days down to 10 minutes was achieved accompanied by significantly improved product yields. The robustness of the method was confirmed by 18 additional examples including aromatic, aliphatic, and heterocyclic amines and acids. The obtained agonists were screened for biological activity at 1 μM concentration and few structure–activity relations have been established.

Supporting Information