期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 137, 期 -, 页码 63-75出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.05.036
关键词
Glycine receptor; Allosteric potentiator; Pain; Parallel synthesis; Pharmacophore-based virtual screen
Glycine receptors (GlyRs) are pentameric glycine-gated chloride ion channels that are enriched in the brainstem and spinal cord where they have been demonstrated to play a role in central nervous system (CNS) inhibition. Herein we describe two novel classes of glycine receptor potentiators that have been developed using similarity- and property-guided scaffold hopping enabled by parallel synthesis and pharmacophore-based virtual screening strategies. This effort resulted in the identification of novel, efficient and modular leads having favorable in vitro ADME profiles and high CNS multi-parameter optimization (MPO) scores, exemplified by azetidine sulfonamide 19 and aminothiazole sulfone (ent2)-20. (C) 2017 Elsevier Masson SAS. All rights reserved.
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