Discovery of potent aryl-substituted 3-[(3-methylpyridine-2-carbonyl) amino]-2,4-dimethyl-benzoic acid EP4 antagonists with improved pharmacokinetic profile

Bioorganic & Medicinal Chemistry Letters
Maria-Jesus BlancoAlan M Warshawsky

Abstract

Two new series of EP4 antagonists containing a 3-methylaryl-2-carbonyl core have been identified. One series has a 3-substituted-phenyl core, while the other one incorporates a 3-substituted pyridine. Both series led to compounds with potent activity in functional and human whole blood (hWB) assays. In the pyridine series, compound 7a was found to be a highly potent and selective EP4 antagonist, with suitable rat and dog pharmacokinetic profiles.

References

Jan 29, 2014·Current Drug Targets·Shashank Misra, Kulbhushan Sharma
Feb 1, 2014·Nature Reviews. Drug Discovery·Andrew L HopkinsCharles H Reynolds

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Citations

Nov 15, 2016·Expert Opinion on Investigational Drugs·Sabine GröschGerd Geisslinger
Jun 13, 2017·Pharmacology Research & Perspectives·Srinivasan ChandrasekharMark G Chambers
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Melissa J Buskes, Maria-Jesus Blanco

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