Issue 6, 2017

Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain. Part 1: 4-acylamino derivatives

Abstract

The synthesis of a new series of 4-acylaminopyrazolo[3,4-d]pyrimidines active on the sigma-1 receptor (σ1R) is reported. Compounds were efficiently prepared using a two to three step process starting from commercially available 1H-pyrazolo[3,4-d]pyrimidin-4-amine. A SAR study shows that the σ1R requires the presence of relatively highly lipophilic substituents at opposite sides of the central scaffold, while selectivity versus the σ2R can be improved by shortening the distance of the basic nitrogen to it. Compound 9a was among the most active and selective in vitro derivatives and exhibited potent antinociceptive properties in several pain models in mice, indicating its antagonistic behaviour.

Graphical abstract: Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain. Part 1: 4-acylamino derivatives

Supplementary files

Article information

Article type
Research Article
Submitted
16 Feb 2017
Accepted
07 Apr 2017
First published
20 Apr 2017

Med. Chem. Commun., 2017,8, 1235-1245

Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain. Part 1: 4-acylamino derivatives

J. L. Díaz, J. Corbera, R. Cuberes, M. Contijoch, R. Enrech, S. Yeste, A. Montero, A. Dordal, X. Monroy and C. Almansa, Med. Chem. Commun., 2017, 8, 1235 DOI: 10.1039/C7MD00077D

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