TOPIC

Tricyclic Triazoles as σ1Receptor Antagonists for Treating Pain

Journal

Journal of Medicinal Chemistry

Author(s)

Díaz, J. L., Cuevas, F., Oliva, A. I., Font, D., Sarmentero, M. Á., Álvarez-Bercedo, P., López-Valbuena, J. M., Pericàs, M. A., Enrech, R., Montero, A., Yeste, S., Vidal-Torres, A., Álvarez, I., Pérez, P., Cendán, C. M., Cobos, E. J., Vela, J. M., & Almansa, C

Year

2021

The synthesis and pharmacological activity of a new series of 5a,7,8,8a-tetrahydro-4H,6H-pyrrolo[3,4-b][1,2,3]triazolo[1,5-d][1,4]oxazine derivatives as potent sigma-1 receptor (σ1R) ligands are reported. A lead optimization program aimed at improving the aqueous solubility of parent racemic nonpolar derivatives led to the identification of several σ1R antagonists with a good absorption, distribution, metabolism, and excretion in vitro profile, no off-target affinities, and characterized by a low basic pKa (around 5) that correlates with high exposure levels in rodents. Two compounds displaying a differential brain-to-plasma ratio distribution profile, 12lR and 12qS, exhibited a good analgesic profile and were selected as preclinical candidates for the treatment of pain.

Go to journal

Get in Touch

We strive to provide the best for our customers, and we are always ready to help. Please let us know if you have a question for us.

Follow us