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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 (?1R) 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 ?1R requires the presence of relatively highly lipophilic substituents at opposite sides of the central scaffold, while selectivity versus the ?2R 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.

SUBMITTER: Diaz JL

PROVIDER: S-EPMC6072305 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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

Díaz José Luis JL Corbera Jordi J Cuberes Rosa R Contijoch Montserrat M Enrech Raquel R Yeste Sandra S Montero Ana A Dordal Albert A Monroy Xavier X Almansa Carmen C

MedChemComm 20170420 6

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 ...[more]

PMID: 30108834

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