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Updated: Jul 10, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors
Bernard Côté1, Louise Boulet, Christine Brideau
1Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que., Canada. bernard_cote@merck.com
Abstract:
Phenanthrene imidazole 3 (MF63) has been identified as a novel potent, selective, and orally active mPGES-1 inhibitor. This new series was developed by lead optimization of a hit from an internal HTS campaign. Compound 3 is significantly more potent than the previously reported indole carboxylic acid 1 with an A549 whole cell IC(50) of 0.42 microM (50% FBS) and a human whole blood IC(50) of 1.3 microM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100mg/kg.
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